Structured Product Labeling Validation Rules for Drug Registration and Listing

Structured Product Labeling (SPL)

Implementation Guide with Validation

Procedures

Technical Specifications Document

This Document is incorporated by reference into the following Guidance Document(s):

Guidance for Industry – Electronic Submission of Lot Distribution Reports

Guidance to industry - Providing Regulatory Submissions in Electronic Format – Content of Labeling

Guidance for Industry - Providing Regulatory Submissions in Electronic Format – Drug Establishment

Registration and Drug Listing

Guidance for Industry - SPL Standard for Content of Labeling Technical Questions and Answers

Guidance for Industry - Indexing Structured Product Labeling (Final)

Guidance for Industry: Self-Identification of Generic Drug Facilities, Sites, and Organizations

Guidance for Industry - Electronic Drug Product Reporting for Human Drug Compounding Outsourcing

Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act

Guidance for Industry - Registration of Human Drug Compounding Outsourcing Facilities Under Section

503B of the FD&C Act

Guidance for Industry - DSCSA Implementation: Annual Reporting by Prescription Drug Wholesale

Distributors and Third-Party Logistics

Guidance for Industry - Compounding Animal Drugs from Bulk Drug Substances

Guidance for Industry - Providing Regulatory Submissions in Electronic Format — Content of the Risk

Evaluation and Mitigation Strategies Document Using Structured Product Labeling

Guidance for Industry - Format and Content of a REMS Document

Registration and Listing of Cosmetic Product Facilities and Products: Guidance for Industry

For questions regarding these technical specifications document, contact s[email protected].

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Biologics Evaluation and Research (CBER)

Center for Drug Evaluation and Research (CDER)

Center for Veterinary Medicine (CVM)

Office of Chief Scientist (OCS)

December 2023

SPL Implementation Guide with Validation Procedures v1

Structured Product Labeling (SPL)

Implementation Guide with Validation Procedures

Version 1 Revision 202312080859

1 Introduction ................................................................................................................. 9

1.1 Organization ........................................................................................................9

1.2 Validation Procedures ..........................................................................................9

2 SPL Documents in General ....................................................................................... 10

2.1 SPL Header ........................................................................................................10

2.1.1 General ...................................................................................................... 10

2.1.2 XML references ........................................................................................ 11

2.1.3 Document information .............................................................................. 12

2.1.4 Author Information ................................................................................... 14

2.1.5 Identified Organizations............................................................................ 15

2.1.6 Address ..................................................................................................... 16

2.1.7 Telecommunication Addresses ................................................................. 17

2.1.8 Contact Party ............................................................................................. 19

2.1.9 “Doing Business As” (DBA) Name .......................................................... 19

2.1.10 Core Document Reference ........................................................................ 20

2.1.11 Predecessor Document .............................................................................. 21

2.2 SPL Body ...........................................................................................................22

2.2.1 Sections and subsections ........................................................................... 22

2.2.2 Text ........................................................................................................... 25

2.2.3 Images ....................................................................................................... 30

2.2.4 Highlights .................................................................................................. 31

2.2.5 Product Data Elements Section ................................................................. 34

3 Product Data Elements .............................................................................................. 36

3.1 Product in General .............................................................................................37

3.1.2 Equivalence to other Products, Product Source ........................................ 40

3.1.3 Additional Identifiers for this Product ...................................................... 42

3.1.4 Ingredient .................................................................................................. 43

3.1.5 Packaging .................................................................................................. 46

3.1.6 Kits, Parts, Components and Accessories ................................................. 49

3.1.7 Marketing Category and Application Number ......................................... 54

3.1.8 Marketing status ........................................................................................ 59

3.1.9 Characteristics ........................................................................................... 64

3.1.10 Combination Product Type ....................................................................... 67

3.1.11 Production Amount ................................................................................... 68

3.2 Drug, Biologics, Dietary Supplement and Medical Food Products ...................69

3.2.1 Code and Name ......................................................................................... 69

3.2.2 Product source ........................................................................................... 73

3.2.3 Active ingredient ....................................................................................... 74

3.2.4 Active moiety ............................................................................................ 76

3.2.5 Reference Ingredient for Strength ............................................................. 77

3.2.6 Inactive ingredient .................................................................................... 77

3.2.7 Packaging .................................................................................................. 78

1 Introduction

3.2.8 Parts........................................................................................................... 79

3.2.9 Marketing Category .................................................................................. 80

3.2.10 Marketing Status and Date ........................................................................ 82

3.2.11 DEA schedule ........................................................................................... 83

3.2.12 Solid Oral Drug Product characteristics ................................................... 83

3.2.13 Color ......................................................................................................... 84

3.2.14 Shape ......................................................................................................... 85

3.2.15 Size ............................................................................................................ 85

3.2.16 Scoring ...................................................................................................... 86

3.2.17 Imprint code .............................................................................................. 86

3.2.18 Flavor ........................................................................................................ 87

3.2.19 Image for Solid Oral Dosage Forms ......................................................... 87

3.2.20 Route of administration............................................................................. 88

3.3 Device Product ...................................................................................................89

3.3.1 Item Code and Name ................................................................................ 89

3.3.2 Additional Device Identifiers .................................................................... 90

3.3.3 [RESERVED] ........................................................................................... 91

3.3.4 Device Ingredient ...................................................................................... 91

3.3.5 [RESERVED] ........................................................................................... 91

3.3.6 [RESERVED] ........................................................................................... 91

3.3.7 Device Parts .............................................................................................. 91

3.3.8 Part of Assembly ....................................................................................... 92

3.3.9 Regulatory Identifiers ............................................................................... 92

3.3.10 Marketing status and date ......................................................................... 94

3.3.11 Device Characteristics .............................................................................. 94

3.3.12 Reusability ................................................................................................ 95

3.3.13 [RESERVED] ........................................................................................... 96

3.3.14 Sterile Use ................................................................................................. 96

3.4 Cosmetic Product ...............................................................................................96

3.4.1 Cosmetic Product Item Code .................................................................... 96

3.4.2 Cosmetic Product Name ........................................................................... 96

3.4.3 Cosmetic Product Category ...................................................................... 97

3.4.4 Cosmetic Ingredient ................................................................................ 101

3.4.5 Cosmetic Parts ........................................................................................ 102

3.4.6 Marketing status and date ....................................................................... 103

3.4.7 Product Web Page Link .......................................................................... 103

3.4.8 Professional Use...................................................................................... 103

3.4.9 Image of Label for Cosmetics ................................................................. 104

3.5 Summary of Product Data Elements ................................................................104

4 Drug and Biologics Labeling, Listing, and other Product Submissions ................. 105

4.1 Header ..............................................................................................................105

4.1.1 Document Type ....................................................................................... 105

4.1.2 Labeler information ................................................................................ 106

4.1.3 Registrant information ............................................................................ 106

4.1.4 Establishment information ...................................................................... 107

4.1.5 Business Operation Product .................................................................... 111

4.2 Body .................................................................................................................112

SPL Implementation Guide with Validation Procedures v1

4.2.1 Required Sections ................................................................................... 112

4.2.2 Reporting Period (for certain submissions) ............................................ 114

5 NDC/NHRIC Labeler Code Request ...................................................................... 117

5.1 Header ..............................................................................................................117

5.1.1 Document type ........................................................................................ 117

5.1.2 Labeler information ................................................................................ 118

5.1.3 Labeler Detail Information ..................................................................... 119

5.1.4 Labeler US Agent ................................................................................... 120

5.1.5 Labeler Operation ................................................................................... 120

5.1.6 FDA-Initiated Labeler Code Inactivation ............................................... 122

5.2 Body - Empty ...................................................................................................123

6 Establishment registration ....................................................................................... 124

6.1 Header ..............................................................................................................124

6.1.1 Document type ........................................................................................ 124

6.1.2 Registrant information ............................................................................ 125

6.1.3 Establishment Information ...................................................................... 126

6.1.4 Establishment US agent .......................................................................... 127

6.1.5 Import business ....................................................................................... 128

6.1.6 Establishment operation .......................................................................... 129

6.1.7 Business Operation Qualifier .................................................................. 130

6.2 Body - Empty ...................................................................................................131

7 Out of Business Notification ................................................................................... 132

7.1 Header ..............................................................................................................132

7.1.1 Document type ........................................................................................ 132

7.2 Body - Empty ...................................................................................................132

8 Pharmacologic Class Indexing ................................................................................ 134

8.1 Header ..............................................................................................................134

8.1.1 Document type ........................................................................................ 134

8.1.2 Author information ................................................................................. 134

8.2 Body .................................................................................................................135

8.2.1 Pharmacologic Class Indexing Section ................................................... 135

8.2.2 Pharmacologic Class Indexing ................................................................ 135

8.2.3 Pharmacologic Class Definition ............................................................. 136

9 Dietary Supplement Labeling ................................................................................. 138

9.1 Header ..............................................................................................................138

9.1.1 Document Type ....................................................................................... 138

9.1.2 Labeler information ................................................................................ 138

9.1.3 Registrant information ............................................................................ 138

9.2 Body .................................................................................................................139

9.2.1 Required Sections ................................................................................... 139

10 Medical Food Labeling ....................................................................................... 140

10.1 Header ..............................................................................................................140

10.1.1 Document Type ....................................................................................... 140

10.1.2 Labeler information ................................................................................ 140

10.1.3 Registrant information ............................................................................ 140

10.1.4 Establishment information ...................................................................... 141

10.2 Body .................................................................................................................142

1 Introduction

10.2.1 Required Sections ................................................................................... 142

11 Medical Device Labeling .................................................................................... 143

11.1 Header ..............................................................................................................143

11.1.1 Document Type ....................................................................................... 143

11.1.2 Labeler information ................................................................................ 143

11.2 Body .................................................................................................................144

11.2.1 Required Sections ................................................................................... 144

12 Billing Unit Indexing .......................................................................................... 145

12.1 Header ..............................................................................................................145

12.1.1 Document Type ....................................................................................... 145

12.1.2 Author ..................................................................................................... 145

12.2 Body .................................................................................................................145

12.2.1 Indexing Section ..................................................................................... 145

12.2.2 NDC ........................................................................................................ 146

12.2.3 Billing Unit ............................................................................................. 146

13 Generic User Fee Facility Self-Identification ..................................................... 148

13.1 Header ..............................................................................................................148

13.1.1 Document type ........................................................................................ 148

13.1.2 Registrant information ............................................................................ 148

13.1.3 Facility Information ................................................................................ 149

13.1.4 Facility operation .................................................................................... 150

13.1.5 Business Operation Qualifier .................................................................. 151

13.2 Body - Empty ...................................................................................................152

14 [RESERVED] ..................................................................................................... 153

15 Indexing - Product Concept ................................................................................ 154

15.1 Header ..............................................................................................................154

15.1.1 Document type ........................................................................................ 154

15.1.2 Author information ................................................................................. 154

15.1.3 Reference Labeling ................................................................................. 154

15.2 Body .................................................................................................................155

15.2.1 Product Concept Indexing Section.......................................................... 155

15.2.2 Abstract Product/Part Concept ................................................................ 155

15.2.3 Ingredient ................................................................................................ 156

15.2.4 Abstract Product Concept Code Specification ........................................ 157

15.2.5 Abstract Kit Concept Code Specification ............................................... 159

15.2.6 Application Product/Kit Concept ............................................................ 161

15.2.7 Marketing Category and Application Number ....................................... 162

15.2.8 Application Product/Kit Concept Code Specification ............................ 162

16 Lot Distribution Report ....................................................................................... 164

16.1 SPL Header ......................................................................................................164

16.1.1 Document type ........................................................................................ 164

16.1.2 Author information ................................................................................. 164

16.1.3 Bulk-Lot Manufacturers.......................................................................... 165

16.2 Body .................................................................................................................166

16.2.2 Data Elements Section ............................................................................ 166

16.2.3 Product Data – Single Licensed Product ................................................ 167

16.2.4 Dosing Specification ............................................................................... 168

SPL Implementation Guide with Validation Procedures v1

16.2.5 Fill Lot .................................................................................................... 168

16.2.6 Bulk Lot(s) .............................................................................................. 169

16.2.7 Label Lot(s) (Final Container Lot) ......................................................... 171

16.2.8 Container Data Elements ........................................................................ 172

16.2.9 Containers Distributed ............................................................................ 173

16.2.10 Containers Returned Data ................................................................... 174

16.2.11 Product Data – Kit with Multiple Licensed Products ......................... 174

17 [RESERVED] ..................................................................................................... 176

18 Wholesale Drug Distributor/Third-Party Logistics Facility Report ................... 177

18.1 Header ..............................................................................................................177

18.1.1 Document type ........................................................................................ 177

18.1.2 Reporter information ............................................................................... 177

18.1.3 Facility Information ................................................................................ 178

18.1.4 Facility Business Operation .................................................................... 180

18.1.5 License .................................................................................................... 180

18.1.6 Business Operation Qualifier .................................................................. 184

18.1.7 Approval Disciplinary Action ................................................................. 184

18.2 Body - Empty ...................................................................................................186

19 40 CFR 180 TOLERANCE ................................................................................ 187

19.1 Header ..............................................................................................................187

19.1.1 Document type ........................................................................................ 187

19.1.2 Author Information ................................................................................. 187

19.1.3 Docket Number ....................................................................................... 187

19.2 Body .................................................................................................................188

19.2.1 Main Sections.......................................................................................... 188

19.2.2 Sub-Section ............................................................................................. 188

19.2.3 Tolerance Specification .......................................................................... 189

19.2.4 Tolerance Range and Commodity .......................................................... 191

19.2.5 Specific Sections and Sub-Sections ........................................................ 192

20 Indexing - Biologic or Drug Substance .............................................................. 193

20.1 Header ..............................................................................................................193

20.1.1 Document Type ....................................................................................... 193

20.1.2 Author ..................................................................................................... 193

20.1.3 Related Document ................................................................................... 193

20.2 Body .................................................................................................................194

20.2.2 Index Data Element Section(s) in General.............................................. 195

20.2.3 New (or only) Index Data Element Section ............................................ 196

20.2.4 Old Index Data Element Section............................................................. 196

20.2.5 Biologic/Drug Product Information ........................................................ 197

20.2.6 Specified Substance ................................................................................ 197

21 Indexing - Warning Letter Alert ......................................................................... 199

21.1 Header ..............................................................................................................199

21.1.1 Document Type ....................................................................................... 199

21.1.2 Author ..................................................................................................... 199

21.1.3 Reference Labeling ................................................................................. 199

21.2 Body .................................................................................................................200

21.2.1 Indexing Section ..................................................................................... 201

1 Introduction

21.2.2 Warning Letter Alert Data Element ........................................................ 201

21.2.3 Warning Letter Date Element ................................................................. 202

22 [RESERVED] ..................................................................................................... 203

23 Risk Evaluation and Mitigation Strategy (REMS) ............................................. 204

23.1 REMS Document .............................................................................................204

23.1.1 Document type ........................................................................................ 204

23.1.2 REMS Author information ..................................................................... 204

23.1.3 REMS Related Document ....................................................................... 205

23.2 Body .................................................................................................................205

23.2.1 REMS Sections and Subsections ............................................................ 205

23.2.2 REMS Product ........................................................................................ 206

23.2.3 Marketing Category and Application Number ....................................... 208

23.2.4 REMS Summary ..................................................................................... 209

23.2.5 REMS Data Elements ............................................................................. 210

23.2.6 REMS Data Elements: Protocol.............................................................. 211

23.2.7 REMS Data Elements:Requirement .......................................................... 212

23.2.8 REMS Approval...................................................................................... 216

23.2.9 REMS Material ....................................................................................... 217

23.2.10 REMS Electronic Resource Information ............................................ 219

24 [RESERVED] ..................................................................................................... 221

25 [RESERVED] ..................................................................................................... 222

26 [RESERVED] ..................................................................................................... 223

27 [RESERVED] ..................................................................................................... 224

28 Blanket No Changes Certification of Product Listing Data................................ 225

28.1 Header ..............................................................................................................225

28.1.1 Document type ........................................................................................ 225

28.1.2 Establishment Information ...................................................................... 225

28.1.3 NDC/ISBT Product Codes ...................................................................... 226

28.1.4 Authorized Agent .................................................................................... 228

28.2 Body - Empty ...................................................................................................228

29 Human and Animal Salvaged Drug Products ..................................................... 229

29.1 Header ..............................................................................................................229

29.1.1 Document type ........................................................................................ 229

29.1.2 Establishment Information ...................................................................... 230

29.1.3 Business operation .................................................................................. 230

29.2 Body .................................................................................................................231

29.2.2 Lot number .............................................................................................. 231

29.2.3 Container Data Elements ........................................................................ 233

30 FDA-Initiated Compliance Action – Drug Listing Inactivation ......................... 235

30.1 Header ..............................................................................................................235

30.1.1 Document type ........................................................................................ 235

30.1.2 Author information ................................................................................. 235

30.1.3 Reference Document ............................................................................... 235

30.2 Body .................................................................................................................237

30.2.2 Inactivated or Reactivated Listing’s NDC(s) .......................................... 237

30.2.3 Compliance Action – Inactivation and Reactivation Status ................... 238

31 FDA-Initiated Compliance Action – Establishment Registration Inactivation .. 240

SPL Implementation Guide with Validation Procedures v1

31.1 Header ..............................................................................................................240

31.1.1 Document type ........................................................................................ 240

31.1.2 Author information ................................................................................. 240

31.1.3 Inactivated or Reactivated Establishments ............................................. 240

31.1.4 Compliance Action – Inactivation and Reactivation Status ................... 242

31.1.5 Reference Document ............................................................................... 242

31.2 Body - Empty ...................................................................................................243

32 Drug Interactions Indexing ................................................................................. 245

32.1 Header ..............................................................................................................245

32.1.1 Document type ........................................................................................ 245

32.1.2 Author information ................................................................................. 245

32.1.3 Reference Labeling ................................................................................. 245

32.2 SPL Body .........................................................................................................246

32.2.2 Sections ................................................................................................... 246

32.2.3 Interaction ............................................................................................... 247

32.2.4 Contributing Factor ................................................................................. 247

32.2.5 Consequence (Risk) ................................................................................ 248

33 National Clinical Trials Number Indexing ......................................................... 250

33.1 Header ..............................................................................................................250

33.1.1 Document type ........................................................................................ 250

33.1.2 Author information ................................................................................. 250

33.1.3 Reference Labeling ................................................................................. 250

33.2 Body .................................................................................................................251

33.2.2 National Clinical Trials Number ............................................................. 251

34 [RESERVED] ..................................................................................................... 253

35 Cosmetic Facility Registration ............................................................................ 254

35.1 Header ..............................................................................................................254

35.1.1 Document type ........................................................................................ 254

35.1.2 Authorized Agent Information (Additional Contact) ............................. 255

35.1.3 Submitter Name and Signature (Legal Authenticator) ........................... 256

35.1.4 Facility Information ................................................................................ 256

35.1.5 Facility US Agent ................................................................................... 258

35.1.6 Parent Company ...................................................................................... 258

35.1.7 Small Business Designation .................................................................... 259

35.1.8 Facility Operation ................................................................................... 259

35.2 Body .................................................................................................................259

35.2.2 Cosmetic Product .................................................................................... 260

35.2.3 Responsible Person (Organization)......................................................... 261

36 Cosmetic Product Listing .................................................................................... 262

36.1 Header ..............................................................................................................262

36.1.1 Document Type ....................................................................................... 262

36.1.2 Labeler (“responsible person” as per label) ............................................ 262

36.1.3 Registrant ................................................................................................ 263

36.1.4 Responsible person further details .......................................................... 264

36.1.5 Facility information ................................................................................ 265

36.1.6 Facility Product Link .............................................................................. 267

36.1.7 Submitter Name and Signature (Legal Authenticator) ........................... 268

1 Introduction

36.2 Body .................................................................................................................269

36.2.1 Required Sections ................................................................................... 269

36.2.2 Cosmetic Product .................................................................................... 269

Appendix ......................................................................................................................... 272

List of Tables ...............................................................................................................272

SPL Implementation Guide with Validation Procedures v1

1 Introduction

Structured Product Labeling (SPL) is a Health Level Seven (HL7) standard based on

Clinical Document Architecture and HL7 Reference Information Model (RIM)

accredited by the American National Standards Institute (ANSI) for the exchange of

product information. Structured Product Labeling documents include a header and

body. The header includes information about the document such as the type of

product, author and versioning. The body of the document includes product

information in both structured text and data element formats. The United States Food

and Drug Administration (FDA) uses SPL documents to exchange information

covering a growing number of product related topics.

This document provides technical conformance criteria for SPL documents used by

FDA. This combines the information previously covered in separate implementation

guide and validation procedures documents.

A link to the latest SPL schema and

controlled terminology used in SPL and other technical documents may be found on

the FDA Data Standards Council web site at: https://www.fda.gov/industry/fda-

resources-data-standards/structured-product-labeling-resources.

1.1 Organization

This document is divided into three parts. The first part of this document describes

the technical conformance criteria that are applicable to header and body of the SPL

document Independent of the information being exchanged. The second part of the

document describes product related technical conformance criteria. The third part

describes the technical conformance criteria applicable to the type of information

being exchanged.

1.2 Validation Procedures

Detailed validation procedures are presented at the end of most sub-sections and are

clearly marked with the heading “Validation Procedures.” These procedures can be

used by humans as check-lists to verify if their submission is correct. The validation

procedures are written specific and operational so that they may be checked by

systems processing SPL documents. Each validation procedure has a unique

paragraph number. These paragraph numbers are generally stable over time, but they

may change between versions of the document when – rarely – a validation procedure

is inserted between existing ones; normally, however, new validation procedures are

appended to the end of their respective sub-sections.

Instead of 2 documents that both contain details on the structure of SPL files for various purposes with

examples, explanations and conformance criteria at varying degree of detailing, the combined document is

a systematic compilation of all such technical information in a new topical organization. As SPL is used for

an increasing number of different types of products or aspects about products, the old organization became

difficult to read and to maintain consistently. The new unified implementation guide with topical

organization combines the discussion of consideration and detailed technical conformance rules for each

aspect or use of SPL in one place.

2 SPL Documents in General

2.1 SPL Header

2.1.1 General

Validation Procedures

2.1.1.1 XML is well formed and valid against the schema

2.1.1.2 There are no data elements and attributes in addition to those described in this

document

Certain exceptions apply to this rule, notably any default attribute that validating

schemas would create are by default part of the document. These need not be stated,

but cannot reasonably be forbidden.

<value xsi:type=“ED” representation=“TXT” integrityCheckAlgorithm=“SHA-

1”/>

</characteristic>

<value xsi:type=“ED” representation=“TXT” integrityCheckAlgorithm=“SHA-

1”/>

</observationMedia>

</effectiveTime>

</quantity>

</asContent>

</actDefinition>

</relatedDocument>

SPL Implementation Guide with Validation Procedures v1

2.1.1.3 There are no spaces in codes

2.1.1.4 Codes do not have a codeSystemName attribute

2.1.1.5 Display names are case insensitive

2.1.1.6 There are no spaces in id extensions

2.1.1.7 Letters in Globally Unique Identifiers (GUID) are lower case

2.1.1.8 There are no empty or incomplete elements except, in certain circumstances,

code, title, text, and time (an id has a root, a code has a code system).

2.1.1.9 Characteristics have a class code of “OBS” or no class code at all.

2.1.1.10 There is no confidentiality code on anything but inactive ingredients, identified

substance, registrant, and assigned establishments outside establishment

registrations.

2.1.1.11 If there is a confidentiality code, then the code is “B” and the codeSystem is

“2.16.840.1.113883.5.25”

2.1.2 XML references

This information includes the location of the current stylesheet for the FDA view of

the SPL and the location of the current schema. The start of the SPL file is the same

for every SPL document and is as follows:

<?xml version="1.0" encoding="UTF-8"?>

<?xml-stylesheet

href="https://www.accessdata.fda.gov/spl/stylesheet/spl.xsl"

type="text/xsl"?>

<document xmlns="urn:hl7-org:v3"

xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"

xsi:schemaLocation="urn:hl7-org:v3

https://www.accessdata.fda.gov/spl/schema/spl.xsd">

Validation Procedures

2.1.2.1 XML reference is for version 1.0 and encoding “UTF-8”.

2.1.2.2 There is an xml-stylesheet reference to

“https://www.accessdata.fda.gov/spl/stylesheet/spl.xsl”.

2.1.2.3 The schemaLocation of the urn:hl7-org:v3 namespace is provided as

“https://www.accessdata.fda.gov/spl/schema/spl.xsd”.

2 SPL Documents in General

2.1.2.4 There are no processing instructions other than the xml and xml-stylesheet

declarations.

2.1.2.5 There are no comments.

2.1.2.6 SPL file name is the document id followed by “.xml”

2.1.2.7 A submission contains only the SPL file whose name ends in ‘.xml’ and, if

appropriate, associated image files whose names end in '.jpg' except if the

document types are Wholesale Drug Distributors and Third-Party Logistics

Facility Report (75030-7) or Risk Evaluation & Mitigation Strategies document

(82351-8) having associated pdf files whose names end in '.pdf'.

2.1.2.8 All image files associated with the SPL document are actually referenced from

that SPL document.

2.1.3 Document information

This provides basic information for the identity of the particular document, its type,

title, date and versioning as a member of a document set.

Terminology: The SPL document types are from LOINC. This code provides

information about the subject matter of the document e.g., prescription animal drug.

<code code="51725-0" codeSystem="2.16.840.1.113883.6.1"

displayName="Establishment registration"/>

<title>Establishment Registration</title>

• The <id root> is a Globally Unique Identifier (GUID) and is unique for each

version of the document. Letters used in a GUID are lower case.

• The <code> is the LOINC code which provides information on the document

type.

• The <title> data element is used for the title for the document, if necessary.

Images are not included in the title. Multiple lines may be used in the title

with each line separated by the line break <br/> tag. (note: all titles can also

be as follows: <title mediaType="text/x-hl7-title+xml">).

• The <effectiveTime> provides a date reference to the SPL version including

the year, month and day as yyyymmdd.

• The <setId> is a GUID and is a unique identifier for the document that

remains constant through all versions/revisions of the document.

SPL Implementation Guide with Validation Procedures v1

• The <versionNumber> is an integer greater than zero that provides a sequence

to the versions of the document.

Validation Procedures

2.1.3.1 There is a document id

2.1.3.2 id root is a Globally Unique Identifier (GUID).

2.1.3.3 id does not have an extension.

2.1.3.4 id does not match any other id in the document.

2.1.3.5 id (document id) is unique across all documents, sections and any other ids

2.1.3.6 There is a code

2.1.3.7 Code system is 2.16.840.1.113883.6.1

2.1.3.8 Code comes from the Document type list

2.1.3.9 Display name matches the code

2.1.3.10 There are no figures in the title.

2.1.3.11 There is an effective time with at least the precision of day in the format

YYYYMMDD

2.1.3.12 There is a set id

2.1.3.13 The set id is a GUID

2.1.3.14 There is a version number

2.1.3.15 Value of version number is a whole number > 0

2.1.3.16 Value of version number is greater than the value of any previously submitted

version for the same set id

2.1.3.17 The preceding version of this set id has not been replaced by a document with a

different set id, i.e., this set id has not been referenced as a related document of

type "replace" (RPLC) from a document with a different set id.

2 SPL Documents in General

2.1.3.18 If the document type is Recombinant Deoxyribonucleic Acid Construct Label

(78745-7) then there the updated document type is Intentional Animal Genomic

Alteration Label (101437-2).

2.1.3.19 If the previous document type is Recombinant Deoxyribonucleic Acid Construct

Label (78745-7), (for the set id) then it has been replaced with Intentional

Animal Genomic Alteration Label (101437-2).

2.1.4 Author Information

The author information is represented as follows:

Many times the author information is used to represent details on the businesses

responsible for the products. This includes the labeler and registrant and

establishments involved in manufacturing:

The following is a representative coding of the common structures in the header:

<time/>

<name>business name</name>

<addr>

<streetAddressLine>address</streetAddressLine>

<state>state</state>

<postalCode>postal code</postalCode>

<country code="country code"

codeSystem="1.0.3166.1.2.3">country name</country>

</addr>

<name>contact person name for labeler</name>

</contactPerson>

</contactParty>

SPL Implementation Guide with Validation Procedures v1

<name>business name</name>

<id extension="FDA establishment identifier"

root=”2.16.840.1.113883.4.82”/>

<name>Establishment name</name>

<name>business name</name>

</assignedOrganization>

<code code="C73330"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="display name"/>

</actDefinition>

</performance>

</assignedEntity>

</assignedOrganization>

<code code="establishment business operation code"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="display name"/>

</actDefinition>

</performance>

</assignedEntity>

</assignedOrganization>

</assignedEntity>

</representedOrganization>

</assignedEntity>

</author>

</document>

2.1.5 Identified Organizations

Most organizations are identified using Dun and Bradstreet identifiers (DUNS

numbers). These are identifiers with the root 1.3.6.1.4.1.519.1 and an extension.

The only reason for an organization not being identified is if the organization remains

anonymous but has sub-organizations (e.g., a listing file may not contain any

registrant information)

2 SPL Documents in General

<name>buiness name</name>

<name>buiness name</name>

Validation Procedures

2.1.5.1 One id is a DUNS number with the root 1.3.6.1.4.1.519.1, except if the

document type is Cosmetic Product Listing (103572-4), Cosmetic Facility

Registration (103573-2), Cosmetic Facility Registration – Amendment (X8888-

1), Cosmetic Facility Registration - Biennial Renewal (X8888-4), or Cosmetic –

Update (X8888-5).

2.1.5.2 The id (DUNS number) with the root 1.3.6.1.4.1.519.1 has a 9-digit extension

2.1.5.3 There is a name, except if the document is an FDA-Initiated Compliance Action

Drug Registration and Drug Listing Inactivation (89600-1), FDA-Initiated

Compliance Action Drug Registration and Drug Listing Inactivation – Animal

Drug (99282-6), Cosmetic Product Listing (103572-4), Cosmetic Facility

Registration (103573-2), Cosmetic Facility Registration – Amendment (X8888-

1), Cosmetic Facility Registration - Biennial Renewal (X8888-4), or Cosmetic –

Update (X8888-5).

2.1.6 Address

For addresses (addr) the following rules apply

<addr>

<streetAddressLine>1625 29th street</streetAddressLine>

<city>Camden</city>

</addr>

Validation Procedures

2.1.6.1 An address has one or two street address line, city, and country.

2.1.6.2 If there is a country code, then it is an ISO 3-letter country code (code system

“1.0.3166.1.2.3”).

2.1.6.3 If there is no code attribute, then the country name may be the code, otherwise

country is a full country name matching the code.

SPL Implementation Guide with Validation Procedures v1

2.1.6.4 If the country is “USA”, then the contact party’s address has a state (2-letter

abbreviation) and postal code

2.1.6.5 If the country is “USA”, then the postal code is 5 digits with optionally a dash

followed by 4 numbers

2.1.6.6 If the country is not in the postal code validation list, then there is a postal code

2.1.7 Telecommunication Addresses

Some elements may have telecommunication addresses. If an element has

telecommunication addresses it usually allows for a telephone number and an email

address.

...

...

</contactParty>

However, there are exceptions noted in the validation procedures.

Telecommunication addresses are usually provided for an organization’s contact

party, in which case telephone and email are the common standard. In no case is

telephone or email missing for contact party. But in some cases a 3

telecommunication address can be provided with the FAX number:

...

...

</contactParty>

Normally telecommunication addresses are associated with specific contact parties of

organizations as shown above, such as, for registrant contact party or establishment

contact party or labeler contact party. However, in some cases, telephone numbers of

physical facilities can be specified directly without contact party:

...

</assignedOrganization>

In several Establishment/Facility Registrations/Reporting use cases, traditionally the

US Agents and Importers have been provided as abbreviated organizations without

the added complexity of a contact party:

2 SPL Documents in General

...

</assignedOrganization>

Validation Procedures

2.1.7.1 There are two <telecom> elements, except if the document type is Lot

Distribution Data (66105-8) or Indexing - Substance (64124-1) there is one

telecom element, or for Identification of CBER-Regulated Generic Drug Facility

(72090-4) or Generic Drug Facility Identification Submission (71743-9) there

may be a third telecom element, or for any of the Cosmetic Facility Registration

and Cosmetic Product Listing document types where all telecom elements are

optional except in facility contact and U.S. Agent.

2.1.7.2 One telecom value begins with “tel:” and is a telephone number, except if the

document code is Lot Distribution Data (66105-8) or Indexing - Substance

(64124-1) or any of the Cosmetic Facility Registration and Cosmetic Product

Listing document types, other than in facility contact party and U.S. Agent.

2.1.7.3 For telephone numbers, the following general rules apply:

2.1.7.4 Telephone numbers are global telephone numbers;

2.1.7.5 Telephone numbers contain no letters or spaces;

2.1.7.6 Telephone numbers begin with “+”;

2.1.7.7 Telephone numbers include hyphens to separate the country code, area codes

and subscriber number;

2.1.7.8 US telephone numbers have the format +1-aaa-bbb-cccc where “aaa” is the area

code, and “bbb-cccc” the usual digit grouping of a local phone number.

2.1.7.9 Telephone numbers have any extensions separated by “;ext=” (see Uniform

Resource Identifier (URI) for Telephone Numbers RFC 3966).

2.1.7.10 If there is a semicolon in the telephone number, then it is followed by ext.

2.1.7.11 One telecom value begins with “mailto:” and encodes an email address, except

for any of the Cosmetic Facility Registration and Cosmetic Product Listing

document types, other than in facility contact party and U.S. Agent.

2.1.7.12 an email address is of the simple form <username>@<dns-name>

SPL Implementation Guide with Validation Procedures v1

2.1.7.13 If there is a third telecom element (fax number), then its value begins with

“fax:” and its format is the same as for a telephone number.

2.1.8 Contact Party

For most organizations, a contact party may be specified with a contact person as in

the following example:

<addr>

<streetAddressLine>1625 29th street</streetAddressLine>

<city>Camden</city>

</addr>

<name>Bob Jones</name>

</contactPerson>

</contactParty>

Validation Procedures

2.1.8.1 The contactParty has an address element (addr), except if the document is Lot

Distribution Data (66105-8), Wholesale Drug Distributor and Third-Party

Logistics Facility Report (75030-7), Withdrawal of Wholesale Drug Distributors

and Third-Party Logistics Facility Report (77573-4), Blanket No Changes

Certification Of Product Listing (86445-4), Indexing - Substance (64124-1), or

any of the Cosmetic Facility Registration and Cosmetic Product Listing

document types.

2.1.8.2 The contactParty has telephone number and email addresses except for any of

the Cosmetic Facility Registration and Cosmetic Product Listing document

types.

2.1.8.3 There is one contact person name, except for any of the Cosmetic Facility

Registration and Cosmetic Product Listing document types, where the name is

optional.

2.1.8.4 If none of the contact party data are provided, then there is no contact party

element at all.

2.1.9 “Doing Business As” (DBA) Name

...

2 SPL Documents in General

<code code="C117113" displayName="doing business as"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

<name>A.C.M.E. Logistic</name>

</asNamedEntity>

Validation Procedures

2.1.9.1 There is no “doing business as” (DBA) name element, except if the document

type is Wholesale Drug Distributors and Third-Party Logistics Facility Report

(75030-7).

2.1.9.2 DBA name has a name element

2.1.10 Core Document Reference

For some SPL documents it is permitted to specify a “core document” reference. A

document with a core document reference “inherits” all the sections from the

referenced core document and may override certain top-level sections with its own

sections. A core document reference is specified as follows:

...

</relatedDocument>

</document>

The reference contains the setId of the referenced core-document. The document and

the core-document can develop Independently. The core-document may be updated,

but the reference remains to the latest core-document with the same setId. The version

number in the reference may be provided to indicate which version of the core-

document was used when at the time the referencing document was created or

modified.

Validation Procedures

2.1.10.1 There is no document id

2.1.10.2 There is a set id

2.1.10.3 Set id is a GUID

SPL Implementation Guide with Validation Procedures v1

2.1.10.4 Document set id is the set id of a core-document.

2.1.10.5 If there is a version number, then it is a whole number > 0.

2.1.10.6 If there is a version number, then it is less or equal than the version of the

current core document with that set id.

2.1.11 Predecessor Document

Other documents may be merged into this document by providing a reference to the

other predecessor documents that are replaced by this document. Do not provide a

reference to the predecessor document under the same set id as the document being

submitted, as this is implicitly given by the set id and incremented version number of

this document. Only provide references to documents of different set ids. The

reference contains only the id of the other predecessor document, code, the setId and

the version number. All these ids must match the ids of the other documents that had

previously been submitted.

...

<code code="Other Registration Document Type Code"

codeSystem="2.16.840.1.113883.6.1"

displayName="Other Registration Document Type Name"/>

</relatedDocument>

</document>

Validation Procedures

2.1.11.1 There is an id (document id)

2.1.11.2 The id (document id) is a GUID

2.1.11.3 There is a set id

2.1.11.4 The set id is a GUID

2.1.11.5 The set id is different from the present document’s set id.

2.1.11.6 There is a version number, which is a whole number > 0.

2.1.11.7 The set id has been previously submitted.

2 SPL Documents in General

2.1.11.8 Document id and version number match the latest document previously

submitted under that set id excluding any No Change Notifications.

2.1.11.9 Document type matches the latest document type previously submitted under

that set id excluding any No Change Notifications.

2.1.11.10 The referenced document has not already been replaced by another document.

2.2 SPL Body

The body of the SPL document includes structured text such as product labeling and

specific data elements such as ingredients.

2.2.1 Sections and subsections

<code code="34067-9"

codeSystem="2.16.840.1.113883.6.1"

displayName="Indications and Usage"/>

<title>Indications and Usage</title>

<text>labeling text</text>

Sections and subsections have id, title, and code. LOINC codes are used for sections

and subsections codes.

The <title>, if necessary, of the sections and subsections and order of the sections and

subsections in the SPL are used to render the labeling contents. The numbering for

the sections and subsections are included in the <title> text.

In the SPL schema, the <structuredBody> element contains multiple <component>s,

and each <component> contains a <section>.

Sections are used to aggregate paragraphs into logical groupings. The order in which

sections appear in an SPL document is the order the sections will appear when

displayed (rendered) using the standard stylesheet. Major sections defined by the

appropriate labeling regulations (e.g., 21 CRF 201.56 and 57 for human prescription

drugs and 201.66 for human over the counter drugs) such as Indications and Usage

are assigned LOINC codes. Sections that have not been assigned a LOINC code are

SPL Implementation Guide with Validation Procedures v1

assigned the LOINC code for “SPL Unclassified Section”. Major sections may also

be defined by parts of a container or carton label (e.g., Principal Display panel).

<text>

</text>

Each section has a unique identifier (<id>), an <effectiveTime>, and a LOINC code

(i.e., the <code> element). A section may or may not contain a <title>.

The human readable content of labeling is contained within the <text> element in the

<section>. The <section> can be nested to form sub-sections. The schema for

subsections in SPL requires that the nested <section> tag first be nested inside a

<component> tag. Use nested sections to relate paragraphs. The section tag applies to

all of the nested sections. By nesting sections, computer systems can use the section

tags in SPL to display information useful for the care of patients. If information is not

associated with the tag, it will not be displayed.

<text>

</text>

</section>

</component>

</section>

</component>

</section>

Using the following principles for markup of text information improves access to

information in labeling:

• Capture the section heading using the <title> element rather than placing the

text of the title within the <text> element. This allows computer systems to

use and display this information properly.

• Capture the section heading even when the printed label does not include a

heading. For example, tagging a pregnancy statement as a section in a label

that does not have a heading for pregnancy is useful. Computer systems will

be able to use the tag to capture the pregnancy use statement. Omitting the

<title> would prevent the heading from appearing when the SPL is rendered.

2 SPL Documents in General

• Link different parts of the labeling using the ID attribute to the <section>

element. For example, <section ID="Clin_Pharm_Section”> serves as the

target of a <linkHtml> element. Linking to the ID attribute of a section allows

the link to 'reference' the section entirely, e.g., for retrieval of a whole section

in a non-browser interface.

• For container or carton labels, when capturing text and figures outside the

Drug Facts or equivalent sections, separate the text and figures for each

concept using <paragraph> tags.

• The order of the placement of information is the content of the package insert,

the content of the patient information and the carton and container labels with

images.

Validation Procedures

2.2.1.1 Each section has zero to many subsections

2.2.1.2 Each section and subsection has an id root and no extension

2.2.1.3 id root (section id) is a GUID

2.2.1.4 id does not match any other id in the document

2.2.1.5 id (section id) does not match any other id across all sections, documents, or

any id other than the id of the same section previously submitted

2.2.1.6 Each section and subsection has a code

2.2.1.7 Code system is 2.16.840.1.113883.6.1

2.2.1.8 Display name matches the code

2.2.1.9 Each section has an effective time with at least the precision of day in the format

YYYYMMDD, except the SPL Listing Data Elements Section (48780-1) of Lot

Distribution Data (66105-8), Human Compounded Drug Label (75031-5),

Animal Compounded Drug Label (77647-6) and Indexing - Warning Letter Alert

(77288-9) documents, and the SPL Indexing Data Elements Section (48779-3) of

Indexing - Biologic or Drug Substance (77648-4) and Indexing - Warning Letter

Alert (77288-9).

2.2.1.10 There are no figures in the title for a section or subsection.

2.2.1.11 The section for SPL Medguide Section (42231-1) and SPL Patient Package

Insert Section (42230-3) is not a subsection.

SPL Implementation Guide with Validation Procedures v1

2.2.2 Text

<text>

<paragraph>Lorem ipsum dolor sit amet, consectetur adipisicing elit,

sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim

ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip

ex ea commodo consequat. Duis aute irure dolor in reprehenderit in

voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint

occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit

anim id est laborum.</paragraph>

<paragraph>At vero eos et accusamus et iusto odio dignissimos ducimus

qui blanditiis praesentium voluptatum deleniti atque corrupti quos dolores

et quas molestias excepturi sint occaecati cupiditate non provident,

similique sunt in culpa qui officia deserunt mollitia animi, id est laborum

et dolorum fuga.</paragraph>

</text>

</section>

The human readable text content of SPL documents is contained within the <text>

element. The actual content is contained within a <paragraph>, <table>, and/or <list>.

If a section consists only of nested sections, the <text> tag is not included. Elements

that can be used within the <text> element to capture the human readable content of

SPL include paragraphs (<paragraph>), lists (<list>), tables (<table>) and images

(<renderMultimedia>). Elements permitted as children of the <text> element, used as

children of the <paragraph> element or within <table> and <list> include superscripts

(<sup>), subscripts (<sub>), links (<linkHtml>), line breaks (<br>), footnotes

(<footnote>), footnote references (<footnoteRef>). Images may be included in the

content of labeling using the <renderMultiMedia> tag. This tag may be used as a

direct child of <text> for ‘block’ images or as a child of <paragraph> for inline

images.

2.2.2.1 Font effects

There are certain aspects of the rendering of SPL that must be specified in the SPL

source to insure that the content of labeling is formatted correctly when rendered. For

example:

<text>

<paragraph>The next snippet <content styleCode="bold italics">will appear

as bold italics</content> in the rendering.</paragraph>

Will be rendered as:

The next snippet will appear as bold italics in the rendering.

The <content styleCode=””> can also be nested, for example:

<text>

<content styleCode="bold italics"> will appear as bold

italics</content>

2 SPL Documents in General

Can also be represented as:

<text>

<content styleCode="bold”><content styleCode="italics”> will appear as

bold italics.</content></content>

The values for <styleCode> for font effect are bold, italics and underline. To assist

people who are visually impaired, the <styleCode=”emphasis”> is used to prompt

computer screen reader programs to emphasize text such as text in a box warning.

The bold, italics and underline font effects may be used together with each other and

the emphasis styleCode. For example, <content styleCode=”bold”><content

styleCode=”emphasis”> </content></content> will appear as bold and will be

emphasized by the screen reader programs.

A special styleCode is used for recent major changes (see below).

2.2.2.2 Symbols and special characters

Special characters can be included in the text. Superscripts and subscripts are

accomplished using the <sup> and <sub> tags. Because the SPL encoding is UTF-8,

any Unicode character can be included as is. Unicode references may also be inserted

as either &#dddd; where dddd is the Unicode value in decimal notation or &#xdddd;

where dddd is the Unicode value in hexadecimal notation. The font used in the

standard stylesheet is a Unicode font assuring that most Unicode characters will be

rendered correctly if viewed by a browser supporting this font. The only prohibited

characters in XML that can not be directly used are less-than “<” (because SPL XML

tags begin with it) and ampersand “&” (because XML entity references begin with it).

Use of these two symbols must be replaced by the XML entity references <. and

& respectively. For example, “<paragraph>The mean for group 1 was < 13.

</paragraph>” will render as “The mean for group 1 was <13.” and “D&C

Yellow #10” will render as “D&C Yellow #10”.

2.2.2.3 Footnotes

The SPL schema includes a specific footnote element <footnote>. Footnotes are

rendered automatically by the standard SPL stylesheet. <footnoteRef> is used to refer

to another (usually earlier) footnote. For example, “<footnote ID=”testNote”>This is

the footnote content</footnote>” will generate the following footnote at the

appropriate end of a section. “

This is footnote content”

The <footnoteRef> element with the appropriate IDREF attribute, e.g., <footnoteRef

IDREF=”testNote”/> will display the footnote reference in the text corresponding to

the footnote with the same ID, e.g., in this example footnote 6.

Footnotes are rendered by the default stylesheet using Arabic numbers (e.g., 1,2 3,).

Within tables, footnotes are rendered using footnote marks in the series: * † ‡ § ¶ # ♠

SPL Implementation Guide with Validation Procedures v1

♥ ♦ ♣, effectively separating numbered footnotes within general text and footnotes

within tables. Footnotes within tables are rendered at the bottom of the table.

2.2.2.4 Lists

All lists are marked up using the <list> tag, and each item in a list is marked with an

<item> tag. The ‘listType’ attribute identifies the list as ordered (numbered) or

unordered (bulleted). The default numbering and bulleting are controlled by the

stylesheet.

<text>

<paragraph>Lorem ipsum dolor sit amet, consectetur adipisicing elit, sed

do eiusmod tempor incididunt ut labore et ...</paragraph>

<item>Lorem ipsum dolor sit amet,</item>

<item>consectetur adipisicing slit</item>

</list>

<paragraph>At vero eos et accusamus et iusto ...</paragraph>

</text>

Lists featuring a standard set of specialized markers (standard specialized lists) can be

created using the styleCode attribute with the <list> element. Options available for

ordered lists are:

• Arabic (List is ordered using Arabic numerals: 1, 2, 3)

• LittleRoman (List is ordered using little Roman numerals: i, ii, iii)

• BigRoman (List is ordered using big Roman numerals: I, II, III)

• LittleAlpha (List is order using little alpha characters: a, b, c)

• BigAlpha (List is ordered using big alpha characters: A, B, C)

For example: <list listType="ordered" styleCode="LittleRoman">

For unordered lists the following options exist:

• Disc (List bullets are simple solid discs: ●)

• Circle (List bullets are hollow discs: ○)

• Square (List bullets are solid squares: ■)

For example: <list listType=”unordered” styleCode=”Disc”>

In addition to the standard specialized lists, user-defined characters are also permitted

as markers by nesting <caption> within the <item> tag. Note that any character, XML

2 SPL Documents in General

entity, or Unicode symbol, may be used in the <caption>, and that the <caption> for

each <item> are not restricted to the same character.

For example: <item><caption>*</caption> the asterisk is used as item marker

here.<item>

2.2.2.5 Tables

Tables can be created with the full structure (header (e.g., for column names), body

(e.g. for the rows of the table) and footer e.g. for table footnotes)). The element

<tbody> is required for an SPL table while the elements <thead> and <tfoot> are

optional in the SPL schema. The structure will display a standard typographical table

with rules between the caption (table title) and head, the head and body, and the body

and <tfoot>. If a <tfoot> element is included and footnotes are present in a table, then

footnotes are rendered after the existing content of the <tfoot> element.

It is recommended to always start with a standard table (i.e., <thead> and <tbody>

elements) and test to see whether the rendering is unambiguous and interpretable. It is

important that the table communicate labeling content not that it duplicates the

presentation in word processed or typeset versions of the package insert. In the

unusual situation where additional formatting is needed, the rule styleCode specified

or certain attributes may be used to modify the table.

The rule codes are as follows (note that the control names are case sensitive).

• Rule on left side of cell is Lrule

• Rule on right side of cell is Rrule

• Rule on top of cell is Toprule

• Rule on bottom of cell is Botrule

Note: More than one rule control may be used in a cell, e.g., <td styleCode

code=”Botrule Lrule”>Cell content </td>.

Rule control codes should be used only when necessary for the interpretability of the

table. Use of these codes may result in overriding the default rules for tables. Rather

than setting the rule for each cell, table rules may also be controlled according to

entire rows or columns by use of the styleCode attributes with <col>, <colgroup>,

<thead>, <tfoot>, <tbody> and <tr> elements.

To make rowgroups appear with horizontal rules, use the styleCode attribute

"Botrule" with the appropriate <tr> element. The Botrule value is rarely needed on

the <td> element.

SPL Implementation Guide with Validation Procedures v1

The preferred method for using vertical rules is to define colgroup with

styleCode="Lrule” or “Rrule" (or both). Only if this does not yield the desired

vertical rule should the Lrule or Rrule code value with styleCode attributes on the

<td> or <th> element itself be used. Note: In general, vertical rules should not be

used. Good typography for tables means using few vertical rules.

To merge cells vertically and horizontally, the rowspan and colspan attributes should

be used on the <td>element.

To determine the width of a table, the width attribute may be used on the <table>

element and to determine the width of a table column, the width attribute may be used

on the <col> and <colgroup> elements.

For horizontal alignment, the preferred method for aligning cell content within the

margins is to use <col align=”.. ”/> in the <colgroup> element, though this can be

used in the <colgroup> element as well. Valid values for align are “left”, “center”,

“right”, “justify” (for full justification of contents within the cells), and “char” (for

character alignment within the cells). Using the <col align=”.. ”/> markup ensures

that the contents for all cells in the column share the same alignment.

For vertical alignment, the valign attribute can be used within cells. For cases in

which the cell alignment must be different from other cells in the column, align is

also available as an attribute on the other table elements, including <td>.

Markup for table footnote is rendered in the <tfoot> tag. This element does not need

to be included in SPL; the standard stylesheet will include a <tfoot> tag if a

<footnote> element is present within either the <thead> or <tbody> sections. A

<tfoot> section should be included in SPL only if there is additional information other

than footnotes that needs to be rendered in this section.

For table text spacing, in some instances, the use of a “tab” or text indentation is

desirable in a given table cell. In an SPL document, this effect is achieved by using

the nonbreaking space ( ) as if it were a “tab” space. As the following snippet

of XML shows, two nonbreaking spaces were used to offset the word “Male” from

the margin: <td>  Male</td>. The nonbreaking space can also be used

to keep text in a table from breaking inappropriately due to browser resizing.

2.2.2.6 Hypertext links

SPL offers hypertext linking capabilities generally similar to those found in the

HTML specification.

Links are specified by the <linkHtml> construct, where the value for the href attribute

of <linkHtml> (the target of the link) is the ID attribute value of a <section>,

<paragraph>, <table>, <list>, <content>,<renderMultimedia> element. The stylesheet

does not support the styleCode attribute of the <linkHtml> element; if a styleCode is

2 SPL Documents in General

needed for a link, this should be coded via the <content> element within the link as

with other text.

2.2.2.7 Recent major changes in labeling text

SPL offers a notation to identify recent major changes in the labeling text including

table elements <table> and table data <td>. The recent major text is tagged using the

<content styleCode=“xmChange”>. For example,

<text>This is an example of text that is not changed.<content

styleCode=“xmChange”>This is an example of text that is a recent major

change</content>This is an example of changed text that is not considered a

recent major change</text>

Validation Procedures

2.2.2.8 Text is enclosed under <paragraph>, <list>, or <table> elements.

2.2.2.9 The number of table data (<td>) elements is identical to the number of column

(<col>) elements in each table (<table>).

2.2.3 Images

The SPL schema uses <observationMedia> elements to identify graphic files to be

rendered at the locations where they are referenced by <renderMultiMedia> elements

in the <section>. In other words, an image in an SPL will be rendered wherever it is

referenced by the renderMultimedia markup, no matter where the observationMedia

markup appears. The referencedObject attribute of the renderMultiMedia element

identifies the corresponding observationMedia instance by means of its ID identifier

such as <renderMultiMedia referencedObject="MM1"/>

<text>

</text>

<text>descriptive text</text>

</value>

</observationMedia>

</component>

</section>

The <observationMedia> element does not contain the graphics file, but instead

points at the file. The <reference> value is the file name. The file name should not

include spaces. The observationMedia identifies the graphic media type (i.e., JPEG).

In addition, the observationMedia element includes the text description of the image

SPL Implementation Guide with Validation Procedures v1

used by screen reader software for visually impaired users. This is included in the

<text> child of <observationMedia>. Note also that observationMedia is always

contained within a <component> element as illustrated.

For image placement, if an image is a block image (i.e., should appear in its own

space), insert the renderMultimedia tag between <paragraph> elements. If an image is

inline (i.e., should appear alongside text), insert the renderMultimedia tag in the text

of a <paragraph> as appropriate. Inline images are expected to be uncommon and

basically represent symbols that cannot be represented by Unicode characters. In

addition, <caption> are not applicable for inline images since these are not offset

from the surrounding text.

The SPL stylesheet does not perform any resizing graphics or changing the resolution

of graphics files. Thus, all images are rendered in the browser as-is, with all

characteristics of the actual graphic file itself. To ensure that a graphic will appear as

desired, it is very important that the graphic file is edited to a dimension appropriate

for its presentation within the browser. If this is not done, the appearance of the

graphic may not be consistent with the narrative content reducing the readability of

the file. JPEG image file type using appropriate pixels per inch for images for

viewing in a browser using the standard stylesheet.

Validation Procedures

2.2.3.1 There is text

2.2.3.2 Value xsi:type is as above

2.2.3.3 Media type is image/jpeg

2.2.3.4 Reference value is the file name for a valid image

2.2.3.5 Size of image file is less than 1 MB

2.2.3.6 File is a JPEG image and the name has the extension “.jpg”

2.2.3.7 Image components are referenced at least once in the text of any section.

2.2.3.8 Image reference in text has an image “observationMedia” element with a

matching ID in the same document.

2.2.4 Highlights

The actual Highlights of a rendered SPL are constructed from four sources:

“boilerplate” text rendered directly from the stylesheet, information from data

elements inserted into the boilerplate text, <title> in the header which includes the

drug names, dosage form, route of administration, controlled substance symbol and

2 SPL Documents in General

year of initial US approval, and text blocks corresponding to each major highlights

part (Highlights text). Highlights section titles are derived from the FPI section

LOINC codes. The Highlights text is captured for the following sections:

Microbiology, Boxed Warning, Recent Major Changes, Indications and Usage,

Dosage and Administration, Dosage Forms and Strengths, Contraindications,

Warnings and Precautions, Adverse Reactions, Drug Interactions and Use in Specific

Populations.

The text blocks for Highlights are coded with the <excerpt> <highlight> elements of

the major section of labeling in which they are contained.

For example, the Highlights for Indications and Usage are located with the

Indications and Usage section of the labeling. The Highlights text is placed under the

main section and not under subsections. The following is an example:

<code code="43685-7" codeSystem="2.16.840.1.113883.6.1"

displayName="warnings and precautions section"/>

<title>5 WARNINGS AND PRECAUTIONS</title>

<text>

<item>Aplastic anemia has been observed in 8% of recipients and

is irreversible in the majority of patients who experience this. (<linkHtml

href=”#Section_5.1”>5.1</linkHtml>)</item>

<item>Monitor for hematological adverse reactions every 2 weeks

through the second month of treatment (<linkHtml

href=”#Section_5.2”>5.2</linkHtml>)</item>

</list>

</text>

</highlight>

</excerpt>

<title>5.1 Aplastic anemia</title>

<text>

<paragraph>Aplastic anemia has been observed in…..</paragraph>

</text>

</section>

</component>

</section>

</component>

This example illustrates the following principles:

SPL Implementation Guide with Validation Procedures v1

a. The <text> block for the Highlights is included as the <excerpt> <highlight>

<text> children of the respective section. In the example above, the text block

rendered in the highlights section is the child of the “Warnings and Precautions”

section.

b. The coding of the highlights text block is not in a subsection.

c. The text block is rendered similar to any other text block, although in a location

separate from its actual position in the rendered SPL document.

d. Links to the section or subsection where the primary content exists are explicitly

entered in the Highlights text block.

e. Section numbering is included in the title of sections and subsections (e.g., ‘5’ and

‘5.1’, above).

Highlights and labeling boilerplate items include:

• Statement -“Highlights of Prescribing Information”

• Highlights section titles

• Patient counseling statement with information taken from FPI section LOINC

codes for patient information sections, specifically information for patient

section (34076-0), SPL Medguide section (42231-1), SPL patient package

insert section (42230-3) and SPL supplemental patient material (38056-8)

• Revision date is taken from the effective time

• Full Prescribing Information: Contents

• Statement – “Full Prescribing Information”

Validation Procedures

2.2.4.1 There may be excerpts (sections with highlights text).

2.2.4.2 Excerpts occur only in the following sections: Boxed Warning Section (34066-

1), Recent Major Changes Section (43683-2), Indications & Usage Section

(34067-9), Dosage & Administration Section (34068-7), Dosage Forms &

Strengths Section (43678-2), Contraindications Section (34070-3), Warnings

and Precautions Section (43685-7), Adverse Reactions Section (34084-4), Drug

Interactions Section (34073-7), Use in Specific Populations Section (43684-0),

and Microbiology Section (49489-8)

2.2.4.3 If there is an excerpt, then it only has highlight text.

2 SPL Documents in General

2.2.4.4 An excerpt in the Adverse Reactions Section (34084-4) includes the statement:

"to report suspected adverse reactions" and "1-800-332-1088" (different

telephone number for documents of type Vaccine Label (53404-0).

2.2.4.5 If there are highlights excerpts, then the title for the SPL file includes the text

string (without the quotation marks): “These highlights do not include all the

information needed to use” “see full prescribing information for” and “Initial

U.S. Approval”

2.2.5 Product Data Elements Section

Currently most of the time the product data elements are in a separate section of their

own followed by the content of labeling sections that contain only text and no data

elements. Product data element section and other special data elements sections are

described in Section 3 below; this section describes the features used from the free

text (so called “narrative”) part of the SPL documents.

<code code="48780-1" codeSystem="2.16.840.1.113883.6.1"

displayName="SPL product data elements section"/>

</manufacturedProduct>

</subject>

</section>

</component>

The beginning of the product data elements is as follows

<code code="48780-1"

codeSystem="2.16.840.1.113883.6.1"

displayName="SPL product data elements section"/>

Validation Procedures

2.2.5.1 Code, code system and display name are as above

SPL Implementation Guide with Validation Procedures v1

2.2.5.2 There is one or more product, except in Human Compounded Drug Label

(75031-5) and Animal Compounded Drug Label (77647-6) documents.

2.2.5.3 There is an effective time with at least the precision of day in the format

YYYYMMDD.

2.2.5.4 There is only one product data element section.

3 Product Data Elements

This section describes with examples in general the capabilities of the product data

elements that are currently implemented in the scope of this Implementation Guide.

More specific sections follow with more detail and more specific guidelines and

validation procedures. These subsequent sections may constrain and detail what is

described here, but may also introduce details not described here in general. In case of

discrepancies, the later specific ruling preempts the general description given here.

Terminology:

• FDA terminology is used for the proprietary, non proprietary and ingredient

name.

• National Drug Codes (NDC) System is used for

o NDC Labeler Code (4 or 5 digit code (e.g., 0001 or 11111)), to register

the labeler prefix,

o NDC Product Code (8 or 9 characters beginning with the NDC Labeler

Code separated by a hyphen from the product segment of the code

(e.g., 0001-0001 or 11111-001 or 11111-0001)) for products

Independent of packaging, and

o NDC Package Code (10 characters beginning with the NDC Product

Code separated by a hyphen from the package segment of the code

(e.g., 0001-0001-01, 11111-001-01 or 11111-0001-1)) for packaged

products.

• NDC System is also used for identifiers for the National Health Related Item

Code (NHRIC)

o NHRIC Labeler Code (4 or 5 digit code),

o NHRIC Product Code (8, 9 or 10 digits beginning with the NHRIC

Labeler Code separated by a hyphen from the product segment of the

code and

o NHRIC Package Code (10 digits beginning with the NDC Product

Code separated by a hyphen from the package segment of the code).

• ISBT-128 site and product codes are for licensed minimally manipulated cell

products.

• GS1 GTIN and HIBCC codes are used for device item codes.

• FDA Substance Registration System (SRS) is used for the ingredient and

active moiety Unique Ingredient Identifier (UNII).

• The FDA submission tracking system is used for application numbers.

• The National Cancer Institute Thesaurus (NCIt) is used for dosage form,

product characteristics, DEA schedule, unit of presentation, route of

administration and equivalent codes.

• The Unified Codes for Units of Measure (UCUM) is used for the unit of

measure.

• HL7 confidentiality code “B” is for business confidential information.

• FDA Product Classification codes are for device and cosmetic products.

SPL Implementation Guide with Validation Procedures v1

• Codes from the OTC Monograph are used for monograph IDs.

• Cosmetic Listing Number (CLN) assigned to each Cosmetic Product Name

identified in each initial and updated technically valid cosmetic product SPL

file for which a Listing Number has not been previously assigned. The

Cosmetic Listing Number Format:

o Cosmetic Listing Number (CLN) Prefix: 53 -

o Product Segment of CLN: XXXXXX-XXXXXX

o OID for Cosmetic Product Listing is 2.16.840.1.113883.3.9848.

3.1 Product in General

Among the product data elements that are always used are item code and name. These

are children of <manufacturedProduct>.

Item Code is a unique identification of this product description whether or not the

item code is printed on the product itself. Item codes must conform to the ISO 15459

system of codes. National Drug Code (NDC), National Health Related Item Code

(NHRIC), GS1 GTIN, HIBCC all conform to ISO 15459. All these have in common

that they are composed of a company prefix (e.g. NDC labeler segment) followed by

the item reference that is assigned by the owner of the company prefix to create a

unique item code. As long as the item code is unique, the digits (and letters) in it need

not convey any other information.

Names: When specific manufactured or marketed products are described, the name is

the proprietary name as it appears on the label divided between <name> and <suffix>.

The <name> is the initial portion of the proprietary name describing the ingredients

without any other descriptors including trademarks and dosage forms. If necessary,

<suffix> is used for descriptors such as “extended release”. When using the <suffix>,

a space after the proprietary name is added as necessary. Non-proprietary or generic

names of drugs are found in the <genericMedicine><name> element. Device type

codes and descriptions use <asSpecializedKind>.

A brief description is added in the <desc> element that states succinctly the kind of

device. This text should be brief to be able to list it in short summary listings. While

the text can be up to 512 characters in length, it should normally be much shorter so

that it will be useful for listing in tables. A device also has a device-nomenclature

code in the <asSpecializedKind> element. This code comes from the FDA Product

Classification terminology.

Cosmetic Listing Number (CLN): Associated with each product name. For Code

system name ‘Cosmetic Product Listing’ assigned Code system OID is

‘2.16.840.1.113883.3.9848’.

Marketing category and product type: The type of product is indicated by the

“Marketing Category”.

Table 1: Marketing Category and Product Type

3 Product Data Elements

Code

Type

Display Name

C73583

Drug

ANADA

C73584

Drug

ANDA

C132333

Drug

Approved drug product manufactured Under Contract

C95600

Drug

Approved drug product manufactured Under Contract

C73585

Biologic

BLA

C73626

Drug

Bulk ingredient

C98252

Drug

Bulk Ingredient for Animal Drug Compounding

C96793

Drug

Bulk Ingredient for Human Prescription Compounding

C73588

Drug

Conditional NADA

C86952

Dietary Supplement

C94795

Drug

Drug for Further Processing

C80438

Device

Exempt device

C73590

Drug

Export only

C80440

Device

Humanitarian Device Exemption

C75302

Drug

IND

C92556

Drug

Legally Marketed Unapproved New Animal Drugs for

Minor Species

C86964

Medical Food

C175238

Drug or Biologic

Multi-Market Approved Product

C73593

Drug

NADA

C73594

Drug

NDA

C73605

Drug

NDA authorized generic

C132334

Drug

OTC monograph drug product manufactured Under

Contract

C95601

Drug

OTC monograph drug product manufactured Under

Contract

C200263

Drug

OTC Monograph Drug

C80441

Device

Premarket Application

C80442

Device

Premarket Notification

C175462

Drug or Biologic

SIP Approved Drug

C101533

Drug

unapproved drug for use in drug shortage

C73627

Drug

unapproved drug other

C132335

Drug

Unapproved drug product manufactured Under Contract

C95602

Drug

Unapproved drug product manufactured Under Contract

C73614

Drug

unapproved homeopathic

C73613

Drug

unapproved medical gas

C181659

Drug

Outsourcing Facility Compounded Human Drug Product

(Exempt From Approval Requirements)

C96966

Drug

Emergency Use Authorization

The following is an example for a drug product:

SPL Implementation Guide with Validation Procedures v1

<name>proprietary name <suffix>suffix to name</suffix></name>

<formCode code="dose form code"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="display name"/>

<name>non proprietary name</name>

</genericMedicine>

</asEntityWithGeneric>

</manufacturedProduct>

<code code="C73594" displayName="NDA"

codeSystem="2.16.840.1.113883.3.26.1.1" />

</approval>

</subjectOf>

</manufacturedProduct>

</subject>

The following is an example for a device:

<name>proprietary name <suffix>suffix to name</suffix></name>

<desc>Brief description of product (up to 512 characters)</desc>

<code code="product classification code"

codeSystem="2.16.840.1.113883.6.303"

displayName="display name"/>

</generalizedMaterialKind>

</asSpecializedKind>

</manufacturedProduct>

<code code="C80441" displayName="Premarket Application"

codeSystem="2.16.840.1.113883.3.26.1.1" />

</approval>

</subjectOf>

</manufacturedProduct>

</subject>

Validation Procedures

3.1.1.1 There is an Item Code, except for part products not requiring an Item Code or if

the document type is Human Compounded Drug Label (75031-5), Animal

Compounded Drug Label (77647-6), Indexing - Biologic or Drug Substance

3 Product Data Elements

(77648-4) or Risk Evaluation & Mitigation Strategies (82351-8), Indexing –

Risk Evaluation & Mitigation Strategies (82353-4), FDA-Initiated Compliance

Action Drug Registration and Drug Listing Inactivation (89600-1), FDA-

Initiated Compliance Action Drug Registration and Drug Listing Inactivation –

Animal Drug (99282-6), Cosmetic Product Listing (103572-4), Cosmetic

Facility Registration (103573-2), Cosmetic Facility Registration – Amendment

(X8888-1), Cosmetic Facility Registration - Biennial Renewal (X8888-4), or

Cosmetic – Update (X8888-5).

3.1.1.2 General rules about the Item Code are:

3.1.1.3 Code system is 2.16.840.1.113883.6.69 (NDC, NHRIC), 1.3.160 (GS1),

2.16.840.1.113883.6.40 (HIBCC), 2.16.840.1.113883.6.18 (ISBT 128), or

2.16.840.1.113883.3.9848 (Cosmetic Product Listing Number) except if the

document type is Indexing – Product Concept (73815-3).

3.1.1.4 Code is compliant with the code system’s allocation rules.

3.1.1.5 There is a name, i.e., proprietary name of the product as used in product labeling

or in the catalog, except if the document type is Indexing - Product Concept

(73815-3) or FDA-Initiated Compliance Action Drug Registration and Drug

Listing Inactivation (89600-1), or FDA-Initiated Compliance Action Drug

Registration and Drug Listing Inactivation – Animal Drug (99282-6), or if the

marketing statusCode is new or cancelled.

3.1.1.6 If the document type is Human Compounded Drug Label (75031-5) then there

may be an item code.

3.1.1.7 The product item code has not been previously submitted in an NDC reservation

of a different document set id with marketing status new.

3.1.2 Equivalence to other Products, Product Source

The following is for referencing information already submitted for a source drug:

<name>proprietary name <suffix>suffix to name</suffix></name>

<code code="source NDC Product Code"

codeSystem="2.16.840.1.113883.6.69"/>

</definingMaterialKind>

</asEquivalentEntity>

SPL Implementation Guide with Validation Procedures v1

This is a special case of referencing other products for various purposes. Another

purpose is for products that are updated with improvement, where it may be useful to

indicate a succession to a previous version of the product identified by the item code

of the predecessor product. This can be done using the equivalence relationship with

<asEquivalentEntity> with a different Role code as in Table 2:

...

The following equivalence codes are defined:

Table 2: Equivalence Codes

Equivalence

Code

Same

C64637

Predecessor Product

pending

Product source may be specified under a product

or under parts

<part>

Validation Procedures

3.1.2.1 As equivalent entity class code is as above

3.1.2.2 If there is a classCode, it is “EQUIV”.

3.1.2.3 Code and code system are as above, except if the document type is Indexing -

Product Concept (73815-3) or Indexing - Warning Letter Alert (77288-9).

3.1.2.4 Source NDC product code (Defining material kind code) matches an NDC

product code (Item Code) in an SPL file with a different set id.

3.1.2.5 Equivalent Item Code is not the same as the Item Code for the product

3 Product Data Elements

3.1.2.6 Equivalent Item Code is not the same as the Item Code for another equivalence

stated for this product, except if the document type is Indexing - Product

Concept (73815-3).

3.1.2.7 The Source NDC product code is not currently inactivated by an FDA Agency

Initiated Compliance Action.

3.1.2.8 There is only one product source per product.

3.1.2.9 If the document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6) then there is no product source.

3.1.2.10 If the source NDC product code (Defining Material Kind Code) matches an

NDC product code (Item Code) with a marketing end date in an SPL file with a

different set id, then the repackager’s/relabeler’s NDC product code is

associated with a marketing end date which is identical or prior to the marketing

end date for the source NDC product code (Defining Material Kind Code).

3.1.3 Additional Identifiers for this Product

A multitude of other identifiers may be assigned to some products by various parties,

manufacturers, distributors, wholesalers, regulators. These identifiers are of a varying

quality in terms of control for uniqueness and meaning. They may be unique item

codes from other ISO 15459 item code systems, or they may be less well defined

codes such as “model number” or “catalog number” etc. While those “model

numbers” or “catalog numbers” are often not safe for referencing, such identifiers are

customer facing and may encode minor product variants, which would be recognized

by customers and hence listing such identifier cross references can aid in finding the

correct item code.

...

<code code="other identifier type code"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="model number"/>

HL7 requires any identifier to be made globally unique, therefore submitters must

acquire an OID of their own through any of several sources. Submitters must not

allow conflicting assignments of model numbers among their own products.

Submitters can still create unique identifiers from these model numbers by giving

different root OIDs for each kind of identifiers that may be in conflict. Once a

company has acquired a root OID this root OID can be freely sub-divided. For

example, ACME Fine Devices Inc. may have acquired the OID

2.16.840.1.113883.3.98765 from the HL7 registry. ACME then decided to use a sub-

branch .2 under their OID to manage model numbers for the models from models

SPL Implementation Guide with Validation Procedures v1

release before 2007 and sub-branch .5 for models released after 2007. There is no

specific rule that must be obeyed when sub-dividing OIDs as long as it results in the

concatenation of model number code and codeSystem OID to be a unique identifier.

Different types of such identifications may be assigned different codes from the NCI

Thesaurus for Model Number, Catalog Number and possibly other “types” of

numbers:

Table 3: Miscellaneous Identifier Types

Identifier Type

Code

Description

Model Number C99286 the exact model number found on the device label or

accompanying packaging.

Catalog Number C99285 the exact number as it appears in the manufacturer's catalog,

device labeling, or accompanying packaging

Reference

Number

C99287 any secondary product identifier

3.1.4 Ingredient

Ingredients may be specified for products

and parts.

<part>

Ingredient information includes the class code specifying the type of ingredient (e.g.,

active, inactive), code, name, and strength, and possibly active moiety name(s) and

identifier and a reference ingredient name and identifier.

</quantity>

<name>active ingredient name</name>

<name>active moiety name</name>

</activeMoiety>

3 Product Data Elements

<name>reference substance name</name>

</definingSubstance>

</asEquivalentSubstance>

</ingredientSubstance>

</ingredient>

Devices too may have active ingredients as discussed above (device with embedded

ingredient.)

The ingredient element is also used to specify that a product “may contain” a certain

substance (e.g., latex, milk, nuts) or that it “does not contain” such substances (e.g.,

wheat gluten).

“May contain” is expressed by specifying the ingredient using the class code

“CNTM” without any quantity; e.g., product may contains latex:

<name>NATURAL LATEX RUBBER</name>

“Does not contain” is expressed by specifying the ingredient using the class code

“CNTM” without a quantity with numerator 0 (zero); e.g. product is gluten free:

</quantity>

<name>WHEAT GLUTEN</name>

If the ingredient comes from a product (such as in Human Compounded Drug Labels,

75031-5) one can specify the product item code for the ingredient as a source product,

or, when the product item code is an NDC, called simply the ingredient’s source

NDC.

...

</substanceSpecification>

</subjectOf>

</ingredient>

SPL Implementation Guide with Validation Procedures v1

Active ingredient class codes are “ACTIB”, “ACTIM”, and “ACTIR”. See Section

3.2.3 for details on active ingredients. Other ingredient classes exist aside from active

ingredients. Drugs have inactive ingredients (also called “excipients”) described in

Section 3.2.6. Devices, dietary supplements, cosmetics and certain compounded drugs

may also have ingredients whose class is not further specified other than that it is an

“ingredient” (INGR):

<name>ASCORBIC ACID</name>

Validation Procedures

3.1.4.1 There is a class code.

3.1.4.2 There may be a strength with a numerator and denominator

3.1.4.3 Numerator and denominator have a value greater than zero and a unit, except the

numerator when the ingredient class code is “CNTM”.

3.1.4.4 Unit comes from the UCUM units of measures list

3.1.4.5 For percentages numerator unit is not 1, instead use a volume unit for volume

fractions and a mass unit for mass fractions.

3.1.4.6 The denominators values and units for all ingredients in this product are the

same.

3.1.4.7 There is an ingredient code with code and code system, except for cosmetics

product listings, where the code is optional.

3.1.4.8 Code system is 2.16.840.1.113883.4.9 except if the document type is Human

Compounded Drug Label (75031-5.)

3.1.4.9 The same ingredient substance code (UNII) is not used more than once per

product.

3.1.4.10 There is an ingredient name.

3.1.4.11 Name matches the code (UNII)

3.1.4.12 If the document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6) then there are source(s) of the active

ingredient(s) which are identified using an item code (ingredient source NDC),

or as ingredients (with the classCode “INGR”) such as a dietary supplement

ingredients.

3 Product Data Elements

3.1.4.13 If the document type is not Human Compounded Drug Label (75031-5) or

Animal Compounded Drug Label (77647-6) then there is no ingredient source

product item code (ingredient source NDC).

3.1.4.14 Ingredient source product item code (source NDC) has been previously

submitted (i.e. is a known listed product).

3.1.4.15 If the document type is Animal Compounded Drug Label (77647-6), then the

source of the active ingredient (bulk or finished drug(s)) identified by the item

code (source NDC product code) has that same active ingredient as the

compounded drug product.

3.1.4.16 If the document type is, Animal Compounded Drug Label (77647-6), then the

source of the active ingredient (bulk or finished drug(s)) identified by the item

code (source NDC product code) can consist of more than one active ingredient,

and in that case all the source's active ingredients must be mentioned in the

compounded drug product.

3.1.5 Packaging

The packaging includes the quantity of product in the package and the package type

and Package Item Code (such as NDC Package Code or other Item Code for the

package).

Packaging may be specified for the product,

for parts,

<part>

and for packages.

The format for packaging specification is:

For example,

SPL Implementation Guide with Validation Procedures v1

</quantity>

<formCode code="value" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="display name"/>

</containerPackagedProduct>

</asContent>

Validation Procedures

3.1.5.1 A product may have an “as content” (package information) element (optional for

parts)

3.1.5.2 There is a quantity, except if the document type is FDA-Initiated Compliance

Action Drug Registration and Drug Listing Inactivation (89600-1), or FDA-

Initiated Compliance Action Drug Registration and Drug Listing Inactivation –

Animal Drug (99282-6); see Section 30.

3.1.5.3 Quantity (for package information) includes a numerator and denominator.

3.1.5.4 Numerator (for package amount) has a value greater than zero and a unit

3.1.5.5 If the product has parts, then the initial numerator value and unit is “1”

3.1.5.6 Unit of the numerator (for package amount) of the initial package is the same as

the units for the denominators of all the ingredient quantities (strengths)

3.1.5.7 Unit of the numerator (for package amount) of an outer package is the same as

the unit for the denominator of the quantity of the inner package

3.1.5.8 Denominator has value 1 and either no unit or unit “1”.

3.1.5.9 There is a form code, except if the document type is FDA-Initiated Compliance

Action Drug Registration and Drug Listing Inactivation (89600-1), or FDA-

Initiated Compliance Action Drug Registration and Drug Listing Inactivation –

Animal Drug (99282-6); see Section 30.

3.1.5.10 Code system for form code is 2.16.840.1.113883.3.26.1.1.

3.1.5.11 Display name matches form code

3.1.5.12 There is a package item code with code and code system for outermost package,

except for parts or if the document type is Human Compounded Drug Label

(75031-5) or Animal Compounded Drug Label (77647-6).

3 Product Data Elements

3.1.5.13 If document type is Cellular Therapy (60684-8), Plasma Derivative (60683-0),

Vaccine Label (53404-0), then there is a package item code with code and code

system for the inner, unit of use package, except if the inner package is wrapped

into a pouch (C43200) the item code may be on the pouch level.

3.1.5.14 If the document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6) and if there is a product NDC, then there

should be an outermost package NDC.

3.1.5.15 If the package item code has been previously submitted, then the package form

code and quantity value and unit are the same as in the most recent submission

for this item code.

3.1.5.16 If the package item code is mentioned elsewhere in the document, then the

package form code and quantity value and unit are the same and the content of

both packages have an Item Code that is the same.

3.1.5.17 Package item code does not match any other package item code in the same

package hierarchy.

3.1.5.18 If the package item code is an NDC/NHRIC (i.e., if the root is

“2.16.840.1.113883.6.69”), then the following procedures apply:

3.1.5.19 NDC/NHRIC package item code is 10 digits (excluding any hyphens).

3.1.5.20 NDC/NHRIC package item code contains three segments divided by hyphens.

3.1.5.21 The first two segments of the NDC/NHRIC package item code matches the

NDC/NHRIC product/item code.

3.1.5.22 The third segment of the NDC/NHRIC package item code is numeric.

3.1.5.23 If the package item code is an ISBT 128 code (i.e., if the root is

“2.16.840.1.113883.6.18”), then the following procedures apply:

3.1.5.24 ISBT 128 package item code has three segments divided by hyphens.

3.1.5.25 The first two segments of the ISBT 128 package item code matches the ISBT

128 Product Item Code.

3.1.5.26 The third segment contains two digits.

3.1.5.27 Package Item Code code system is 2.16.840.1.113883.6.69 (NDC, NHRIC),

1.3.160 (GS1), 2.16.840.1.113883.6.40 (HIBCC), 2.16.840.1.113883.6.18

(ISBT 128), or 2.16.840.1.113883.3.9848 (Cosmetic Product Listing Number).

SPL Implementation Guide with Validation Procedures v1

3.1.5.28 Package Item Code is compliant with the code system’s allocation rules.

3.1.5.29 If the document type is not for Bulk Ingredient (53409-9), Bulk Ingredient –

Animal Drug (81203-2), Drug for Further Processing (78744-0), OTC Animal

Drug Label (50577-6), OTC Type A Medicated Article Animal Drug Label

(50576-8), OTC Type B Medicated Feed Animal Drug Label (50574-3), OTC

Type C Medicated Feed Animal Drug Label (50573-5), Prescription Animal

Drug Label (50578-4), VFD Type A Medicated Article Animal Drug Label

(50575-0), VFD Type B Medicated Feed Animal Drug Label (50572-7), VFD

Type C Medicated Feed Animal Drug Label (50571-9), Cosmetic (58474-8),

Dietary Supplement (58476-3), Medical Food (58475-5), Human Compounded

Drug Label (75031-5), Animal Compounded Drug Label (77647-6), Lot

Distribution Data (66105-8), Licensed Vaccine Bulk Intermediate Label (53406-

5), Recombinant Deoxyribonucleic Acid Construct Label (78745-7), Intentional

Animal Genomic Alteration Label (101437-2), FDA-Initiated Compliance

Action Drug Registration and Drug Listing Inactivation (89600-1), FDA-

Initiated Compliance Action Drug Registration and Drug Listing Inactivation –

Animal Drug (99282-6), or Animal Cells, Tissues, and Cell and Tissue Based

Product Label (98075-5), then a combination product type characteristic is on

the inner-most packaging.

3.1.6 Kits, Parts, Components and Accessories

Products may be combined in various ways such as:

• Drug kit with a device part

• Device kit with a drug part

• Device with an embedded drug

• Drug in a delivery device

• Products sold separately but meant to be used together

Kits and Parts: When products have more than one part, each part is described under

<partProduct>. The total amount of the part in the product is included as follows:

<part>

</quantity>

Currently, when a drug product has parts, it is considered a Kit indicated by the

formCode for KIT:

3 Product Data Elements

<name>Easy-Go PreciFuse PorterPump Kit</name>

<formCode code=" C47916" displayName="KIT"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

Device products may also be kits (in this case a device with FDA product

classification code but also with formCode specifying KIT. However, devices

themselves may also be specified with parts, such as distinguishing component

options or field replaceable parts, in this case the top-level device need not have a

formCode for KIT:

<name>name of device</name>

<desc>brief description of device</desc>

<part>

</quantity>

<desc>brief description of device part</desc>

Drug Kit with a Device Part: This sort of kit has been known from SPL R4 as well,

examples being drugs sold as a kit with an applicator device.

<formCode code="C47916" displayName="KIT"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

<part>

<numerator value="amount of this part’s content in one kit"

unit="unit for amount"/>

</quantity>

<code code="NDC code of drug part"

codeSystem="2.16.840.1.113883.6.69"/>

<formCode code="form code of drug part"

displayName="form name of drug part"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

SPL Implementation Guide with Validation Procedures v1

<numerator value="amount of this part in its package"

unit="unit of amount"/>

</quantity>

<code code="NDC code of part’s package"

codeSystem="2.16.840.1.113883.6.69"/>

<formCode code="package type"

displayName="package type name"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

</containerPackagedProduct>

</asContent>

</partProduct>

</part>

<part>

</quantity>

<code code="item code of this device part"

codeSystem="item code system OID"/>

<name>name of device part</name>

<desc>description of device part</desc>

<code code="product classification code of device part"

codeSystem="2.16.840.1.113883.6.303"

displayName="display name of device part"/>

</generalizedMaterialKind>

</asSpecializedKind>

</partProduct>

</part>

Device Kit with a Drug Part:

<code code="item code of device kit"

codeSystem="item code system OID"/>

<desc>brief description of kit</desc>

<formCode code="C47916" displayName="KIT"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

<code code="product classification code of kit"

displayName="display name of kit"

codeSystem="2.16.840.1.113883.6.303"/>

</generalizedMaterialKind>

</asSpecializedKind>

<part>

same as device part above

</part>

3 Product Data Elements

<part>

same as drug part above

</part>

Device with an embedded drug: For example, a drug eluting stent with an

embedded active ingredient. Notice that such products do not involve kits and parts:

<code code="device item code"

codeSystem="device item code system OID"/>

<name>device name</name>

<desc>brief description</desc>

<code code="product classification code of device"

displayName="display name of device"

codeSystem="2.16.840.1.113883.6.303"/>

</generalizedMaterialKind>

</asSpecializedKind>

<code code="UNII code of active ingredient"

codeSystem="2.16.840.1.113883.4.9"/>

<name>paclitaxel</name>

Drug in a delivery device: For example, drug in pre-filled syringe. Note that the

syringe filled with the drug is a different product than the empty syringe. Hence it

would not be correct to put the item code for the empty syringe on the one filled with

the drug. In fact, since the pre-filled syringe already has (or should have) an NDC

code, there is no need for another item code for it. However, one may want to refer to

the item code for the empty syringe as a generalization of the filled syringe:

<code code="NDC code drug"

codeSystem="2.16.840.1.113883.6.69"/>

<formCode code="form code of drug"

displayName="form display name of drug"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

</ingredient>

<numerator value="amount of drug in prefilled device"

unit="unit of amount"/>

</quantity>

SPL Implementation Guide with Validation Procedures v1

<code code="NDC code for prefilled device"

codeSystem="2.16.840.1.113883.6.69"/>

<formCode code="form code of prefilled device"

displayName="form display name of prefilled device"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

<code code="item code of empty device"

codeSystem="item code system of empty device"/>

<desc>brief description of empty device</desc>

<code code="product classification code of device"

displayName="display name of device"

codeSystem="2.16.840.1.113883.6.303"/>

</generalizedMaterialKind>

</asSpecializedKind>

Products sold separately but meant to be used together: when products are used

together but packaged separately, the data element <asPartOfAssembly> is used to

identify the other product. The products could be drugs or devices.

<name>name of device</name>

<desc>brief description of device</desc>

</quantity>

<part>

</quantity>

<code code="item code of accessory component"

codeSystem="code system OID"/>

<name>name of accessory component</name>

<desc>brief description of accessory component</desc>

Parts may be specified for the product,

<part/>

and for part products.

3 Product Data Elements

<part>

<part/>

Validation Procedures

3.1.6.1 If the product form code is for a Kit (C47916), then there is one or more parts.

3.1.6.2 Each part has an overall quantity

3.1.6.3 If there is an “as content” (package information) data element in the part, then

the numerator unit is the same as the numerator unit for the “as content” data

element

3.1.6.4 If there is no “as content” (package information) data element in the part, then

the numerator unit is 1, except if the document type is Indexing - Product

Concept (73815-3) or marketing status is new or cancelled.

3.1.6.5 If there is a code, then the general rules for product code apply (see 3.1.1.1ff).

3.1.6.6 There is a name, except if the document type is Indexing - Product Concept

(73815-3).

3.1.6.7 Procedures for source, ingredients, characteristics and packaging are the same as

for products without parts

3.1.6.8 If the product is a kit/co-packaged product with the form code, C47916 (for Kit),

the document type/product type is Bulk Ingredient (53409-9), Human OTC Drug

Label (34390-5) or Human Prescription Drug Label (34391-3), the marketing

start date for the co-packaged product is on or after November 1st, 2020 and the

marketing category is not Cosmetic (C86965), Dietary Supplement (C86952),

Exempt Device (C80438), Humanitarian Device Exemption (C80440), Medical

Food (C86964), Premarket Application (C80441) or Premarket Notification

(C80442), then each inner component product (<partProduct>) with a drug

marketing category (see Table 1) has a unique NDC product code.

3.1.7 Marketing Category and Application Number

The approval structure specifies in the <code> the marketing category under which

the product is approved for marketing. Products marketed under an approved

application have an application number in the <id extension> and application tracking

system under <id root>. Products marketed under a monograph provide the

monograph ID for the monograph <id extension> and the OTC Monograph ID under

<id root>. If there is no application number or monograph ID, the id element is

omitted.

SPL Implementation Guide with Validation Procedures v1

<id extension="application, monograph ID, or monograph number"

root="FDA document tracking system OID, OTC Monograph ID OID, or

CFR OID"/>

<code code="code for marketing category"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="display name"/>

</effectiveTime>

</territory>

</territorialAuthority>

</author>

</approval>

</subjectOf>

Marketing category is connected through the <subjectOf> element which may appear

on the main product:

or on parts:

<part>

Example:

<code code="C73594"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="NDA"/>

Validation Procedures

3.1.7.1 There is one marketing category for every product and product part, except if the

document type is Cosmetic Product Listing (103572-4), Cosmetic Facility

Registration (103573-2), Cosmetic Facility Registration – Amendment (X8888-

1), Cosmetic Facility Registration - Biennial Renewal (X8888-4), Cosmetic –

Update (X8888-5), Indexing – Product Concept (73815-3), Indexing - Warning

3 Product Data Elements

Letter Alert (77288-9), or Out of Business Notification (53411-5), FDA-Initiated

Compliance Action Drug Registration and Drug Listing Inactivation (89600-

1),or FDA-Initiated Compliance Action Drug Registration and Drug Listing

Inactivation – Animal Drug (99282-6), or there is no marketing status other

than new or cancelled.

3.1.7.2 There is a marketing category code.

3.1.7.3 Code comes from the Marketing category list.

3.1.7.4 Display name matches the code

3.1.7.5 Code system is 2.16.840.1.113883.3.26.1.1

3.1.7.6 Territorial authority is as above

Marketing Category vs. Application Number

The following are validation procedures relating marketing category to application

numbers:

3.1.7.7 If the code is C73583 (ANADA), C73584 (ANDA), C73585 (BLA), C73588

(conditional NADA), C73593 (NADA), C73594 (NDA), C73605 (NDA

authorized generic), C75302 (IND), C80438 (Exempt device), C80440

(Humanitarian Device Exemption), C80441 (Premarket Application), C80442

(Premarket Notification), C92556 (Legally Marketed Unapproved New Animal

Drugs for Minor Species), C175238 (Multi-Market Approved Product) or

C175462 (SIP Approved Drug), then the id root is 2.16.840.1.113883.3.150

(FDA application tracking system).

3.1.7.8 [RESERVED]

3.1.7.9 If the code is C73583 (ANADA), then the id extension has the prefix “ANADA”

followed by 6 digits

3.1.7.10 If the code is C73584 (ANDA), then the id extension has the prefix “ANDA” or

“BA” followed by 6 digits

3.1.7.11 If the code is C73585 (BLA), then the id extension has the prefix “BLA”

followed by 6 digits

3.1.7.12 If the code is C73593 (NADA) or C73588 (Conditional NADA), then the id

extension has the prefix “NADA” followed by 6 digits

3.1.7.13 If the code is C73594 (NDA), or C73605 (NDA authorized generic), then the id

extension has the prefix “NDA” or “BN” followed by 6 digits

SPL Implementation Guide with Validation Procedures v1

3.1.7.14 If the code is C75302 (IND), then the id extension has the prefix “IND”

followed by 6 digits

3.1.7.15 [RESERVED].

3.1.7.16 [RESERVED].

3.1.7.17 [RESERVED].

3.1.7.18 If the code is C92556 (Legally Marketed Unapproved New Animal Drugs for

Minor Species), then the id extension has the prefix “MIF” followed by 6 digits.

3.1.7.19 If the code is C80438 (Exempt device), then the id extension consists of 3 letters

3.1.7.20 If the code is C80440 (Humanitarian Device Exemption), then the id extension

has a prefix “H” followed by 6 digits

3.1.7.21 If the code is C80441 (Premarket Application), then the id extension has a prefix

“P” or “BP” followed by 6 digits

3.1.7.22 If the code is C80442 (Premarket Notification), then the id extension has a

prefix “K” or “BK” followed by 6 digits.

3.1.7.23 If the code is not C73583 (ANADA), C73584 (ANDA), C73585 (BLA), C73588

(Conditional NADA), C73593 (NADA), C73594 (NDA), C200263 (OTC

Monograph Drug), C73605 (NDA authorized generic), C75302 (IND), C80438

(Exempt device), C80440 (Humanitarian Device Exemption), C80441

(Premarket Application), C80442 (Premarket Notification), C132333 (Approved

drug product manufactured Under Contract), C73626 (bulk ingredient), C96793

(bulk ingredient for human prescription compounding), or C98252 (bulk

ingredient for animal drug compounding), C94795 (Drug for further

processing), C92556 (Legally Marketed Unapproved New Animal Drugs for

Minor Species), C175238 (Multi-Market Approved Product) or C175462 (SIP

Approved Drug), then there is no id (application number or regulatory citation

or monograph ID).

3.1.7.24 If the marketing category is Approved drug product manufactured Under

Contract (C132333), then there is an id (application number or regulatory

citation).

3.1.7.25 If the marketing category is Approved drug product manufactured Under

Contract (C132333), then the id extension has the prefix “NDA”, “ANDA”, or

“BLA” followed by 6 digits

3.1.7.26 If the marketing category is Bulk Ingredient (C73626), Bulk Ingredient for

Human Prescription Compounding (C96793), or Bulk Ingredient for Animal

3 Product Data Elements

Drug Compounding (C98252), or Drug for Further Processing (C94795) and

there is an id, then the id extension has the prefix “DMF” or “VMF” followed by

6 digits.

3.1.7.27 If the marketing category is C175238 (Multi-Market Approved Product) or

C175462 (SIP Approved Drug), then the id extension has the prefix NDA, BN,

or BLA followed by 6 digits.

3.1.7.28 If the marketing category is C200263 (OTC Monograph Drug), then the id root

is 2.16.840.1.113883.3.9421 (OTC Monograph ID)

Application Number Consistency

3.1.7.29 If the marketing category is ANDA (C73584), BLA (C73585), or NDA (C73594)

and the SPL document type is not Lot Distribution Data (66105-8) or Vaccine

Label (53404-0) and the application number was already submitted, then the

active ingredient UNIIs are the same as in any previous submission of a product

with the same application number.

3.1.7.30 If the application number is referenced in any Product Concept Indexing file,

then the active ingredient, strength and active moiety match a Product Concept

Indexing file, except if the document type is Lot Distribution Data (66105-8) or

the Indexing – Product Concept (73815-3) file itself.

3.1.7.31 If the application number or citation is referenced in the OTC drug product

application list, then the active ingredient (UNII) and route of administration

associated with the application number matches the entry in the list.

3.1.7.32 If on or after March 23

2020, the application number is present in the NDA to

BLA Conversion List, then the marketing category and application number

prefix must be changed to BLA.

Application Approval Date

3.1.7.33 There may be an approval date (effective time).

3.1.7.34 Approval date (effectiveTime) has a low boundary.

3.1.7.35 Approval date has no high boundary.

3.1.7.36 Approval date has at least the precision of day (YYYYMMDD).

3.1.7.37 If the marketing category code is not C73584 (ANDA), C73585 (BLA), C73594

(NDA), or C175462 (SIP approved drug), then there is no approval date.

3.1.7.38 [RESERVED].

SPL Implementation Guide with Validation Procedures v1

3.1.8 Marketing status

The marketing status provides information on when the product is on or off the

market.

The <code> indicates the activity of “marketing” (or in cases of some packages as

“marketing of sample packages not for sale”). The status of the product is described

in the <statusCode> as either “active” for being on the market or “completed” when a

product is discontinued, or “new” to indicate that the product item code is being

reserved for future use. If the status of the product is cancelled, the NDC reservation

is being cancelled. The date when the product is on or marketed or discontinued is

included in the <effectiveTime>. The date when the product is on the market is

characterized by the <low value>.

Example of a currently marketed product:

</effectiveTime>

</marketingAct>

</subjectOf>

The marketing discontinuation date such as the expiration date of the last lot released

to the market is characterized by the <high value>.

Example of a product that is discontinued:

</effectiveTime>

</marketingAct>

</subjectOf>

For some types of products, a marketing status may be provided on the package level:

3 Product Data Elements

Packages may also be marked as being a drug sample rather than regularly marketed

for sale, Packages that are samples are marked with a marketingAct with the code

C96974 instead of the default marketing act code C53292:

The package marketing status and start and end date (if applicable) are in the same

marketing act.

NDC Code Reservations

For human and animal drug products, NDC code reservations may be sent. This is

done in a listing file, except that content of labeling is not included. The products that

appear in the listing file, do not need a marketing category. Therefore it is not

determined if they are drugs, dietary supplements, cosmetics, devices or biologic

products.

All products require

• a non-proprietary name and

• a dose form.

Note that a proprietary name is not required. Packaging is also not required.

There are 3 types of products with further data requirements.

• drugs need at least one full active ingredient specification, with ingredient

name, UNII, strength, active moiety, and basis of strength.

• dietary supplements need an ingredient (classCode INGR) with ingredient

name and UNII.

A marketing status is required for every product, and the status 'new' indicates that

this product is provided to reserve an NDC product code.

SPL Implementation Guide with Validation Procedures v1

If the marketing status is 'new' a marketing start date should be provided up to 2 years

in the future.

An NDC reservation should be sent as one document those products which will likely

be contained in the same listing file once these products begin to be marketed. The

document set id will then be used by the listing file, i.e., the next version of an NDC

reservation will be a listing file. In a listing file which follows an NDC reservation,

every NDC code that has been reserved needs to be disposed of as either active or

cancelled. The active products become the actively listed products (their marketing

start dates may still be in the future), and the NDC codes that are released will be

marked as cancelled. Once cancelled, these NDC codes do not need to be mentioned

any more in subsequent listing files.

Note that currently it is not expected that NDC reservations will be updated before the

submission of the first listing files.

Validation Procedures

3.1.8.1 There is one marketing status for each top-level product (part products do not

need this), except if the document type is a Animal Compounded Drug Label

(77647-6), Human Compounded Drug Label (75031-5), Cosmetic Product

Listing (103572-4), Cosmetic Facility Registration (103573-2), Cosmetic

Facility Registration – Amendment (X8888-1), Cosmetic Facility Registration -

Biennial Renewal (X8888-4), Cosmetic – Update (X8888-5), Cosmetic –

Abbreviated Renewal (X8888-6), Indexing - Product Concept (73815-3), Lot

Distribution Data (66105-8), Indexing - Warning Letter Alert (77288-9),

Indexing - Biologic or Drug Substance (77648-4), Risk Evaluation & Mitigation

Strategies related (82353-4, 85273-1, 85274-9, 82351-8), Out of Business

Notification (53411-5), FDA-Initiated Compliance Action Drug Registration

and Drug Listing Inactivation (89600-1), or FDA-Initiated Compliance Action

Drug Registration and Drug Listing Inactivation – Animal Drug (99282-6), or

if the SPL file is for Salvaged Drugs (having business operation as salvage,

C70827).

3.1.8.2 There is not more than one marketing status on any one item.

3.1.8.3 Marketing act code is C53292 (or C96974 for packages marked as Drug

Sample) and code system is 2.16.840.1.113883.3.26.1.1.

3.1.8.4 Marketing status code is active, or completed, or new, or cancelled.

3.1.8.5 If the status code is active or new, then there is a low value (marketing start

date) and no high value (marketing end date)

3.1.8.6 If the marketing status code is completed, (discontinued) then there is a low and

high value, except if the document type is Cosmetic Product Listing (103572-4)

or Cosmetic – Update (X8888-5).

3 Product Data Elements

3.1.8.7 The effective time low (marketing start date) and high boundary (marketing end

date) have at least the precision of day in the format YYYYMMDD

3.1.8.8 If there is a high value (marketing end date), then it is not less than the low value

(marketing start date).

3.1.8.9 A marketing status can not be on an inner package, except if the status code is

new.

3.1.8.10 A marketing status can not be on a package for a part of a kit, except if the status

code is new.

3.1.8.11 If the marketing start or end date is on a package, then the start date is not before

the marketing start date of the product and the end date not after the end date of

the product.

3.1.8.12 If any of the products in the document has the application number prefix BA or

BN, then there is no package marketing status.

3.1.8.13 A marketing status can only be on a package in documents of types Human

Prescription Drug Label (34391-3), Human OTC Drug Label (34390-5), Drug

for Further Processing (78744-0), or Bulk Ingredient (53409-9),.

3.1.8.14 If the document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6) then there is no marketing status.

3.1.8.15 A marketing act with code Drug Sample (C96974) is on a package only.

3.1.8.16 If the package is marked as a drug sample, then there is a package item code.

3.1.8.17 If an item has a marketing status active, then at least one of its packages has

either no explicit marketing status at all, or a marketing status of active, except if

the document type is Risk Evaluation & Mitigation Strategies (82351-8),

Cosmetic Product Listing (103572-4), Cosmetic Facility Registration (103573-

2), Cosmetic Facility Registration – Amendment (X8888-1), Cosmetic Facility

Registration - Biennial Renewal (X8888-4), or Cosmetic – Update (X8888-5).

3.1.8.18 If the marketing status code is active or completed, then previous marketing

status code for the item code (NDC product code) is not cancelled.

3.1.8.19 If the marketing status code is completed, then previous marketing status code

for the item code (NDC product code) is not new.

3.1.8.20 If the product is regulated by CDER, then the marketing start or end date are

present at the outermost package level, except for Human Compounded Drug

Label (75031-5) or if marketing status is new or cancelled.

SPL Implementation Guide with Validation Procedures v1

Validation Procedures for NDC Reservations

3.1.8.21 Marketing Status code new or cancelled can not be used at package level.

3.1.8.22 If the marketing status code is new or cancelled, then there is a start marketing

date.

3.1.8.23 If the marketing status code is new, then marketing start date is two years or less

from the date of the submission of the NDC reservation request.

3.1.8.24 If the marketing status code is new or cancelled, then marketing start date is the

same for all products.

3.1.8.25 If the marketing status is cancelled, then there is no marketing end date.

3.1.8.26 If the marketing status code is cancelled, then previous marketing status code

for the item code (NDC product code) is new.

3.1.8.27 If the marketing status code is new or cancelled, then marketing start date cannot

be changed from the previous version.

3.1.8.28 If the marketing status code is new or cancelled, then there is an item code

(NDC product code.)

3.1.8.29 If the marketing status is new, then the product item code has not been

previously submitted in a document of a different set id, except if in that other

document its marketing status is cancelled.

3.1.8.30 If the marketing status code is new or cancelled, then there is a non-proprietary

name (generic medicine name.)

3.1.8.31 If the marketing status code is new or cancelled, then there is an active

ingredient.

3.1.8.32 If any of the products have the marketing status of new, then products having

any active ingredients have the same set of active ingredient substances.

3.1.8.33 Additional validation procedures for NDC product codes apply, see: 3.2.1.2 – 5

and 3.2.1.10 – 15.

3.1.8.34 NDCs can be reserved for drugs in development for a period of up to two years

from the date of receipt of the initial reservation. Once the product(s) included

on an NDC Reservation SPL are ready to launch in the U.S. market, the NDC

Reservation SPL for the product(s) should be revised (change Marketing Status

for ALL products on the SPL to “active”) and converted into a full product

listing SPL.

3 Product Data Elements

3.1.8.35 For NDC reservation questions for CDER products, contact

[email protected].

3.1.8.36 For NDC reservation questions for CVM products, contact

[email protected].

3.1.8.37 If a document contains any item code reservation (marketing status codes is

new), then the SPL document type is Bulk Ingredient (53409-9), Cellular

Therapy (60684-8), Drug for Further Processing (78744-0), Human OTC Drug

Label (34390-5), Human Prescription Drug Label (34391-3), License Blood

Intermediates/Paste Label (53407-3), Licensed Minimally Manipulated Cells

Label (53408-1), Licensed Vaccine Bulk Intermediate Label (53406-5), Non-

Standardized Allergenic Label (53405-7), Plasma Derivative (60683-0),

Standardized Allergenic (60682-2), or Vaccine Label (53404-0) or CVM

products.

3.1.8.38 If a document contains any item code reservation (marketing status codes is new

or cancelled), then there are no marketing status codes of active or completed,

except a part of a kit may be active if the kit is new or cancelled.

3.1.8.39 [POSTPONED] If the product information has previously been submitted, and

the marketing start date is not in the future, then the marketing start date is not

later than the previously submitted marketing start date.

3.1.8.40 [POSTPONED] The product marketing start date is not after any of the start

dates of any active or completed marketing status for any of its previously

submitted packages.

3.1.9 Characteristics

Many characteristics may be specified for products as specified later for specific

product types. In general, the characteristic structure allows specifying any properties

of the product in a code-value pair, the code saying which property is being specified,

the value saying what the property is for the given product. The characteristics

structure connects to the product Role through the subjectOf element.

...

</manufacturedProduct>

<code code="characteristic code"

codeSystem="characteristic code system"/>

Some characteristics may be specified for packaged products:

SPL Implementation Guide with Validation Procedures v1

...

...

</containerPackagedProduct>

<code code="characteristic code"

codeSystem="characteristic code system"/>

Characteristics listed in Table 6 use one of a number of different data types. Each data

type uses slightly different XML elements and attributes as shown in the templates

below:

Characteristic of type physical quantity (PQ):

<code code="characteristic code"

codeSystem="characteristic code system"/>

Characteristic of type number (REAL):

<code code="characteristic code"

codeSystem="characteristic code system"/>

Characteristic of type integer number (INT):

<code code="characteristic code"

codeSystem="characteristic code system"/>

Characteristic of coded type (CV):

<code code="characteristic code"

codeSystem="characteristic code system"/>

<value xsi:type="CV" code="value code"

codeSystem="value code system OID"

displayName="value code display name">

Characteristic of type character string (ST):

3 Product Data Elements

<code code="characteristic code"

codeSystem="characteristic code system"/>

<value xsi:type="ST">value string</value>

Characteristic of type interval of physical quantity (IVL<PQ>):

<code code="characteristic code"

codeSystem="characteristic code system"/>

</value>

Characteristic of type Boolean (true/false value)

<code code="characteristic code"

codeSystem="characteristic code system"/>

Table 4: Characteristic codes and code systems.

Name Code System OID / Code Data

Type

Description

SPL

Characteristics

2.16.840.1.113883.1.11.19255 Used early on with Existing SPL for drugs

characteristics codes that are possibly

applicable for devices:

SPLSIZE

Greatest dimension in millimeter

SPLCOLOR

color code from NCI Thesaurus

SPLIMAGE ED Photographic image of the product for the

purpose of identification, taken under

standardized conditions.

LOINC 2.16.840.1.113883.6.1 Used for metrologically well defined

properties.

NCI Thesaurus 2.16.840.1.113883.3.26.1.1 Used rarely (if at all) for characteristic

codes.

Validation Procedures

3.1.9.1 There is a characteristic property code with code and code system

3.1.9.2 Characteristic property code system is 2.16.840.1.113883.1.11.19255,

2.16.840.1.113883.6.1, or 2.16.840.1.113883.3.26.1.1.

3.1.9.3 There is a characteristic value with specified type appropriate for the

characteristic property.

SPL Implementation Guide with Validation Procedures v1

3.1.9.4 Value type is PQ, INT, IVL_PQ, CV, CE, ST, ED, or BL

3.1.10 Combination Product Type

Combination products are defined in 21 CFR 3.2(e).

To mark products as combination products, the nearest combining package should

bear the combination product type characteristic:

...

...

<code code="SPLCMBPRDTP"

codeSystem="2.16.840.1.113883.1.11.19255"/>

<value code="C102835"

codeSystem="2.16.840.1.113883.3.26.1.1" xsi:type="CV"

displayName="Type 2: Prefilled Drug Delivery Device/System">

Validation Procedures

3.1.10.1 Code and code system are as above

3.1.10.2 Value code system is 2.16.840.1.113883.3.26.1.1

3.1.10.3 Value comes from the Combination Product Type list.

3.1.10.4 Display name matches the value code

3.1.10.5 If the document type is for Bulk Ingredient (53409-9), Bulk Ingredient – Animal

Drug (81203-2), OTC Animal Drug Label (50577-6), OTC Type A Medicated

Article Animal Drug Label (50576-8), OTC Type B Medicated Feed Animal

Drug Label (50574-3), OTC Type C Medicated Feed Animal Drug Label

(50573-5), Prescription Animal Drug Label (50578-4), VFD Type A Medicated

Article Animal Drug Label (50575-0), VFD Type B Medicated Feed Animal

Drug Label (50572-7), VFD Type C Medicated Feed Animal Drug Label

(50571-9), Cosmetic (58474-8), Dietary Supplement (58476-3), Medical Food

(58475-5), Human Compounded Drug Label (75031-5), Licensed Vaccine Bulk

Intermediate Label (53406-5), Drug for Further Processing (78744-0), Animal

Compounded Drug Label (77647-6), or Animal Cells, Tissues, and Cell and

Tissue Based Product Label (98075-5), then there is no combination product

type characteristic on any package.

3.1.10.6 If the dosage form (form code) is Aerosol, Metered (C42960), Gel, Metered

(C60930), Powder, Metered (C42961), Spray, Metered (C42962) or Tablet with

3 Product Data Elements

Sensor (C147579), then there is a combination product type other than Type 0:

Not a Combination Product (C112160).

3.1.10.7 If the dosage form (form code) is Aerosol, Metered (C42960), Gel, Metered

(C60930), Powder, Metered (C42961), or Spray, Metered (C42962), then the

combination product type is Type 2: Prefilled Drug Delivery Device/System

(syringe, patch, etc.) (C102835) or Type 3: Prefilled Biologic Delivery

Device/System (syringe, patch, etc.) (C102836).

3.1.10.8 If the dosage form (form code) is Tablet with Sensor (C147579), then the

combination product type is Type 4: Device Coated/Impregnated/Otherwise

Combined with Drug (C102837).

3.1.10.9 If the package type is Inhaler (C16738), Syringe (C43202), Syringe, Glass

(C43203), or Syringe, Plastic (C43204), then there is a combination product

type other than Type 0: Not a Combination Product (C112160).

3.1.10.10 If the package type is Inhaler (C16738), then the combination product type is

Type 2: Prefilled Drug Delivery Device/System (syringe, patch, etc.) (C102835)

or Type 3: Prefilled Biologic Delivery Device/System (syringe, patch, etc.)

(C102836).

3.1.10.11 If the package type is Syringe (C43202), Syringe, Glass (C43203), or Syringe,

Plastic (C43204), then the combination product type is Type 1: Convenience Kit

of Co-Package (C102834), Type 2: Prefilled Drug Delivery Device/System

(syringe, patch, etc.) (C102835), Type 3: Prefilled Biologic Delivery

Device/System (syringe, patch, etc.) (C102836) or Type 9: Other Type of Part 3

Combination Product (e.g., Drug/Device/Biological Product) (C102842).

3.1.11 Production Amount

The production amount for a package is specified as:

...

...

<code code="SPLPRODUCTIONAMOUNT"

codeSystem="2.16.840.1.113883.1.11.19255"/>

Unlimited production amounts are specified as:

SPL Implementation Guide with Validation Procedures v1

Validation Procedures

3.1.11.1 Code and code system are as above

3.1.11.2 The value is an integer number or null flavor “PINF” to indicate unlimited.

3.2 Drug, Biologics, Dietary Supplement and Medical Food Products

The drug, dietary supplement and medical food product data elements includes the

product codes, proprietary and non proprietary name, dosage form, ingredient and

active moiety name, ingredient identifier, ingredient strength, package quantity, type

and code, marketing category, marketing status, dosage form appearance, DEA

schedule, and route of administration.

Drug products are those products with the appropriate marketing categories listed in

Table 1: Marketing Category and Product Type. Dietary supplement are those

products that are associated with the dietary supplement (C86952) marketing

category. Medical foods are associated with the medical food marketing category

(C86964).

The drug product consists of a product item code (NDC for drugs and NHRIC for

dietary supplements or medical foods), proprietary and non proprietary name, and

dosage form. These are children of <manufacturedProduct>. The proprietary name is

the name as it appears on the label divided between <name> and <suffix>. The

<name> is the initial portion of the proprietary name describing the ingredients

without any other descriptors including trademarks and dosage forms. If necessary,

<suffix> is used for descriptors such as “extended release”. When using the <suffix>,

a space after the proprietary name is added as necessary. If there is no proprietary

name, the non proprietary name is used without any descriptors. The dosage form is

described in <formCode>. The <genericMedicine><name> is the non proprietary

name of the product.

3.2.1 Code and Name

<name>Tazmin <suffix>XR</suffix></name>

<formCode code="C42998"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="tablet"/>

<name>tazminate hydrochloride</name>

</genericMedicine>

Phonetic spellings of the product and generic names may also be specified:

3 Product Data Elements

...

<name>Tazmin <suffix>XR</suffix></name>

...

<name>tazminate hydrochloride</name>

</genericMedicine>

Validation Procedures

3.2.1.1 If the product item code is an NDC/NHRIC (i.e., if the root is

“2.16.840.1.113883.6.69”), then the following procedures apply:

3.2.1.2 Code (NDC/NHRIC product code) has two segments separated by a hyphen

3.2.1.3 The first segment (NDC/NHRIC labeler code) is numeric.

3.2.1.4 Segments (NDC/NHRIC product codes) follow the pattern of 4-4, 5-4 or 5-3

3.2.1.5 The second segment (middle segment of three-segment NDC) is numeric (no

letters allowed).

3.2.1.6 If the product item code is an ISBT 128 code (i.e., if the root is

“2.16.840.1.113883.6.18”), then the following procedures apply:

3.2.1.7 Code contains two segments separated by a hyphen.

3.2.1.8 The first segment contains the ISBT 128 Facility Identification Number (FIN)

beginning with a capital letter A-N, P-Z (i.e., all 26 letters except O) followed

by two alphanumerics A-N, P-Z, 0-9, and two digits.

3.2.1.9 The second segment contains the ISBT 128 product code beginning with a

capital letter (A-Z) followed by 4 digits (0-9) and optionally followed by three

alphanumeric characters.

3.2.1.10 First segment (NDC/NHRIC labeler code) matches a labeler code associated

with the Labeler id (labeler’s DUNS Number) in a previously submitted

NDC/NHRIC Labeler Code or NDC Labeler Code – Animal Drug SPL

document, except for parts.

3.2.1.11 Code (NDC product code) has the same labeler segment as the NDC

product/item code of all top-level products in this document, except under parts.

SPL Implementation Guide with Validation Procedures v1

3.2.1.12 Code (NDC product code) has the same length as all other NDC product/item

codes with the same labeler segment in this document (i.e., all NDC

product/item codes from one labeler have the same consistent length and hence

all package item codes have the same consistent configuration.)

3.2.1.13 Code (NDC product code) has the same length as any other NDC product/item

codes of the same labeler (i.e., all NDC product/item codes by the same labeler

have the same consistent length and hence all package item codes have the same

consistent configuration.)

3.2.1.14 There is only one product data elements section for each NDC product/item

code, i.e., the same product is not described more than once except under parts.

3.2.1.15 If the NDC product/item code is mentioned elsewhere in the document, then the

product and generic name (along with their phonetic names, if any are

specified), dosage form, UNII and strength of all ingredients are the same.

3.2.1.16 There is a product name, except if the document type is Indexing - Product

Concept (73815-3) or there is no marketing status other than new or cancelled.

3.2.1.17 Product name contains no special symbols (e.g., no “®” or “™” etc) and no

“USP” or dosage forms.

3.2.1.18 There may be one phonetic name after the product name.

3.2.1.19 Phonetic name conforms to the phonetic name specification.

3.2.1.20 There is a form code (dosage form), except if the document type is Indexing -

Product Concept (73815-3) or Lot Distribution Data (66105-8), Indexing -

Biologic or Drug Substance (77648-4) or Risk Evaluation & Mitigation

Strategies (82351-8) or Indexing – Risk Evaluation & Mitigation Strategies

(82353-4).

3.2.1.21 Form code (dosage form) has the code system 2.16.840.1.113883.3.26.1.1

3.2.1.22 If the product has parts, then the form code is C47916 (for KIT)

3.2.1.23 Display name matches the code

3.2.1.24 There is a non-proprietary (generic medicine) name, except if the document type

is Indexing - Product Concept (73815-3) or Lot Distribution Data (66105-8) or

Indexing - Biologic or Drug Substance (77648-4) or Indexing – Risk Evaluation

& Mitigation Strategies (82353-4).

3.2.1.25 Non-proprietary (generic medicine) name contains no special symbols (e.g., no

“®” or “™” etc) and no “USP” or dosage forms.

3 Product Data Elements

3.2.1.26 Non-proprietary (generic medicine) name contains no suffix.

3.2.1.27 Non-proprietary (generic medicine) name contains no more than 512 characters.

3.2.1.28 There may be one phonetic name after the non proprietary name.

3.2.1.29 Phonetic name conforms to the phonetic name specification.

3.2.1.30 If the NDC product/item code was previously submitted, then the product name

is same as in the most recent submission for this NDC product/item code.

3.2.1.31 If the NDC product/item code was previously submitted, then the non-

proprietary (generic) name is the same as in the most recent submission for this

NDC product/item code, except if there is no marketing status other than new or

cancelled.

3.2.1.32 If the NDC product/item code was previously submitted, then the active

ingredient UNIIs and active ingredient strengths are the same as in the most

recent submission for this NDC product/item, except if there is no marketing

status other than new or cancelled.

3.2.1.33 If the NDC product/item code was previously submitted, then the product

dosage form is same as in the most recent submission for this NDC product/item

code.

3.2.1.34 If the NDC product/item code was previously submitted, then the product

characteristic of size is the same as in the most recent submission for this NDC

product/item code.

3.2.1.35 If the NDC product/item code was previously submitted, then the product

characteristic of shape is the same as in the most recent submission for this NDC

product/item code.

3.2.1.36 If the NDC product/item code was previously submitted, then the product

characteristic of color are same as in the most recent submission for this NDC

product/item code.

3.2.1.37 If the NDC product/item code was previously submitted, then the product

characteristic of imprint code is the same as in the most recent submission for

this NDC product/item code.

3.2.1.38 [RESERVED]

3.2.1.39 If the NDC product/item code was previously submitted, then the application

number is the same as in the most recent submission for this NDC product/item

SPL Implementation Guide with Validation Procedures v1

code except if after March 23

, 2020 the application number is present in the

NDA to BLA conversion list and changed to the BLA prefix.

3.2.1.40 The dosage form code cannot be “not applicable” (C48624), for document types

other than Recombinant Deoxyribonucleic Acid Construct Label (78745-7), or

Intentional Animal Genomic Alteration Label (101437-2).

3.2.1.41 If the NDC product/item code was previously submitted, then the product

characteristic of flavor is the same as in the most recent submission for this

NDC product/item code.

3.2.1.42 If the NDC product/item code was previously submitted, then the product

characteristic of scoring is the same as in the most recent submission for this

NDC product/item code.

3.2.1.43 If the NDC product/item code was previously submitted, then the product

phonetic name (if specified) is the same as in the most recent submission for this

NDC product/item code.

3.2.1.44 If the NDC product/item code was previously submitted, then the non-

proprietary (generic) phonetic name (if specified) is the same as in the most

recent submission for this NDC product/item code, except if there is no

marketing status other than new or cancelled.

3.2.1.45 If the document type is human OTC drug label (34390-5), then there may be a

cosmetic product category (asSpecializedKind element) with a code (see Section

3.4.3.2 and following).

3.2.1.46 If the document type is not human OTC drug label (34390-5), then there is no

cosmetic product category (asSpecializedKind element).

3.2.2 Product source

<code code=“source product item code”

codeSystem=“2.16.840.1.113883.6.69”/>

Validation Procedures

3.2.2.1 As equivalent entity class code, code and code system are as above

3.2.2.2 If there is a classCode, it is “EQUIV”.

3.2.2.3 If the NDC product source (equivalent product) is present, then the active

ingredients UNII and active ingredients strengths are the same as that of product

source.

3 Product Data Elements

3.2.2.4 If the NDC product source (equivalent product) is present, then the product

characteristic of size is the same as that of the product source.

3.2.2.5 If the NDC product source (equivalent product) is present, then the product

characteristic of shape is the same as that of the product source.

3.2.2.6 If the NDC product source (equivalent product) is present, then the product

characteristics of color are the same as that of the product source.

3.2.2.7 If the NDC product source (equivalent product) is present, then the product

characteristic of imprint code is the same as that of the product source.

3.2.2.8 If the NDC product source (equivalent product) is present, then the product

characteristic of flavor is the same as that of the product source.

3.2.2.9 If the NDC product source (equivalent product) is present, then the product

characteristic of scoring is the same as that of the product source.

3.2.2.10 If the NDC product source (equivalent product) is present, then the product

dosage form is the same as that of the product source.

3.2.2.11 If one of the listed establishment operations is Repack (C73606) or Relabel

(C73607), then there is a product source reference.

3.2.3 Active ingredient

Active ingredients are specified as follows:

</quantity>

<name>tazminate malate</name>

The class code for active ingredient is dependent on the basis of the strength. If the

basis of strength is the active ingredient, the class code is “ACTIB”. If the basis of

strength is the active moiety, the class code is “ACTIM”. If the basis of strength is a

reference drug, the class code is “ACTIR”. The strength is represented as a numerator

and denominator. The UCUM code is used for the unit of measure. The UCUM code

for a unit that is an “each” is “1” Examples of “each” is in the table below.

In most cases, the strength used is that for a single dose following the conventions in

Table 5. In the table, an example of “mass” is milligrams, an example of “volume” is

milliliter, an example of “time” is hour, and an example of “each” is tablet.

SPL Implementation Guide with Validation Procedures v1

Table 5: Conventions for expressing strength

Product Numerator unit Denominator

unit

Oral solid

Mass

Each

Oral liquid

Mass

Volume

Oral powder for reconstitution with a known volume

Mass

Volume

Oral powder for reconstitution with a variable volume

Mass

Each

Suppository

Mass

Each

Injection liquid

Mass

Volume

Injection powder for reconstitution with a known volume

Mass

Volume

Injection powder for reconstitution with a variable volume

Mass

Each

Inhaler powder

Mass

Each

Inhaler liquid

Volume

Each

Inhaler blister

Mass

Each

Topical cream or ointment

Mass

Topical gel or lotion

Mass

Volume

Transdermal patch

Mass

Time

Bulk liquid

Mass

Volume

Bulk solid

Mass

Validation Procedures

3.2.3.1 Class code for active ingredients are ACTIB, ACTIM or ACTIR

3.2.3.2 If the document type is Bulk ingredient (53409-9) or Bulk ingredient – Animal

drug (81203-2) with a marketing category of Bulk ingredient (C73626), then

there is one and only one active ingredient.

3.2.3.3 If the product has no parts and is not a part, then there are one or more active

ingredients except if the document is a Indexing - Product Concept (73815-3) or

Lot Distribution Data (66105-8), Indexing - Warning Letter Alert (77288-9),

Risk Evaluation & Mitigation Strategies (82351-8), Indexing - Risk Evaluation

& Mitigation Strategies (82353-4), or if the SPL file is for Salvaged Drugs, i.e.,

having business operation as salvage (C70827), or there is no marketing status

other than new or cancelled.

3.2.3.4 If the product has parts, then the active ingredients are under parts

3.2.3.5 There is a strength with a numerator and denominator, except if the document is

a Indexing - Biologic or Drug Substance (77648-4).

3.2.3.6 If the document type is Bulk ingredient (53409-9) or Bulk ingredient – Animal

drug (81203-2) with a marketing category of Bulk ingredient (C73626), then

numerator and denominator (representing strength amount) are the same.

3.2.3.7 The strength numerator is based on mass (e.g., mg or g) and not volume (e.g.

mL or L), except for ingredients such as water, alcohol, and gases.

3 Product Data Elements

3.2.3.8 There is a unit of measure in the strength amount's numerator and denominator,

except if the document type is Licensed Minimally Manipulated Cells Label

(53408-1).

3.2.3.9 If the document type is Bulk Ingredient (53409-9), Drug for Further Processing

(78744-0), Human Compounded Drug Label (75031-5), Human OTC Drug

Label (34390-5) or Human Prescription Drug Label (34391-3), then the

numerator unit cannot be “1”.

3.2.3.10 If the document type code is Vaccine Label (53404-0) and if there is any active

ingredient under the main product or under its first part, then at least one active

ingredient code is on the list of active ingredients approved for vaccines.

3.2.4 Active moiety

<name>tazminic acid</name>

Validation Procedures

3.2.4.1 There are one or two active moieties, except if the document type is Indexing -

Biologic or Drug Substance (77648-4).

3.2.4.2 There is an active moiety code (UNII)

3.2.4.3 Code system is 2.16.840.1.113883.4.9

3.2.4.4 There is an active moiety name for each active moiety

3.2.4.5 If the active ingredient is in the active-ingredient-active-moiety-validation-list

(see FDA SPL web page for list https://www.fda.gov/industry/fda-resources-

data-standards/structured-product-labeling-resources), then the active moiety

and basis of strength is the corresponding active moiety and basis of strength

respectively in this list, except if the document type is for Bulk ingredient

(53409-9), Bulk ingredient – Animal drug (81203-2), or Drug for Further

Processing (78744-0) or there is no marketing status other than new or

cancelled.

3.2.4.6 If the active ingredient is not in the active-ingredient-active-moiety-validation-

list (see FDA SPL web page for list https://www.fda.gov/industry/fda-resources-

data-standards/structured-product-labeling-resources), then the active moiety

name does not include any of the names in the active moiety validation (counter

ion) list (see FDA SPL web page for list), except if the word appears by itself

optionally followed by “(ester)”, “cation” or “anion” or “ion”.

SPL Implementation Guide with Validation Procedures v1

3.2.4.7 Active moiety name matches the code (UNII)

3.2.5 Reference Ingredient for Strength

<name>tazemate formate</name>

Validation Procedures

3.2.5.1 If the class code is ACTIR, then there is an asEquivalentSubstance element with

a defining substance, except if there is no marketing status other than new or

cancelled.

3.2.5.2 If the class code is not ACTIR, then there is no asEquivalentSubstance element

3.2.5.3 There is a reference ingredient code

3.2.5.4 Code system is 2.16.840.1.113883.4.9

3.2.5.5 There is a name (preferred substance name)

3.2.5.6 The name matches the code (UNII)

3.2.6 Inactive ingredient

The inactive ingredient includes the inactive ingredient class code, ingredient name,

identifier, and strength. The element <ingredient> is a child of

<manufacturedProduct>. The class code for inactive ingredient is “IACT”. The

strength, if needed, is represented as a numerator and denominator and is described

using UCUM units of measure. If the inactive ingredient is confidential, the

element<ingredient> includes <confidentialityCode code="B"

codeSystem="2.16.840.1.113883.5.25"/>.

</quantity>

<name>inactive ingredient name</name>

</ingredientSubstance>

</ingredient>

3 Product Data Elements

Validation Procedures

3.2.6.1 There are zero to many inactive ingredients.

3.2.6.2 If the document type is human OTC drug label (34390-5), then there is at least

one inactive ingredient, except if the active ingredient(s) comprise 100% of the

product or there is no marketing status other than new or cancelled, or the

inactive ingredient section (51727-6) has the text “none”.

3.2.6.3 Class code is IACT

3.2.6.4 If the product has parts, then the inactive ingredients are under parts

3.2.6.5 If the document type is human OTC drug label (34390-5), then there is no

confidentiality code.

3.2.6.6 There is no ingredient other than active ingredient (having class code ACTIM,

ACTIR, ACTIB), inactive ingredient (having class code IACT), adjuvant

(having class code ADJV), and those having class code CNTM, except if the

document is a Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6) or there is no marketing status other than

new or cancelled.

3.2.7 Packaging

The format for packaging specification is:

</quantity>

<formCode code="C43169"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="bottle"/>

Validation Procedures

3.2.7.1 Every top-level product has an “as content” (package information) element

(optional for parts), except if the document is a Indexing - Product Concept

(73815-3), Lot Distribution Data (66105-8), Indexing - Warning Letter Alert

(77288-9), Indexing - Biologic or Drug Substance (77648-4), Risk Evaluation &

Mitigation Strategies (82351-8) or Indexing – Risk Evaluation & Mitigation

Strategies (82353-4), or there is no marketing status other than new or cancelled,

or if the SPL file is for Salvaged Drugs, i.e., having business operation as

salvage (C70827).

SPL Implementation Guide with Validation Procedures v1

3.2.7.2 If outer package description has a production quantity characteristic, then

document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6).

3.2.7.3 If the document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6) then each outer package description has a

production quantity characteristic.

3.2.7.4 The outer package item code is not associated with another set id except under

parts; therefore the original set ID included in the previous version of the file

with the outer package item code should be used.

3.2.7.5 If the package item code has been previously submitted, then the package form

code (package type) and quantity value and unit are the same as in the most

recent submission for this package item code.

3.2.7.6 There are no drug package characteristics other than the ones mentioned in this

document.

3.2.7.7 The package type code cannot be not applicable (C123723), for documents of

types other than Recombinant Deoxyribonucleic Acid Construct Label (78745-7)

or Intentional Animal Genomic Alteration Label (101437-2).

3.2.8 Parts

Products with one or more parts

<part>

</quantity>

<name>Tazmin <suffix>XR</suffix></name>

<formCode code="C42916"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="capsule, extended release"/>

<name>tazminate hydrochloride</name>

Validation Procedures

3.2.8.1 If the product form code is Kit (C47916), then there is one or more parts

3.2.8.2 If the product has parts, then at least one part has one or more active ingredients.

3 Product Data Elements

3.2.8.3 Procedures for code, name, dosage form code, source, ingredients,

characteristics and packaging are the same as for the main products (see

Sections 3.2.1ff)

3.2.9 Marketing Category

Example:

<code code="C73594"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="NDA"/>

Validation Procedures

3.2.9.1 If the marketing category is Exempt device (C80438), Humanitarian Device

Exemption (C80440), Premarket Application (C80441), or Premarket

Notification (C80442), then there is at least one part.

3.2.9.2 If the document type is: OTC Animal Drug Label (50577-6), OTC Type A

Medicated Article Animal Drug Label (50576-8), OTC Type B Medicated Feed

Animal Drug Label (50574-3), OTC Type C Medicated Feed Animal Drug Label

(50573-5), Prescription Animal Drug Label (50578-4), VFD Type A Medicated

Article Animal Drug Label (50575-0), VFD Type B Medicated Feed Animal

Drug Label (50572-7), VFD Type C Medicated Feed Animal Drug Label

(50571-9), or Animal Cells, Tissues, and Cell and Tissue Based Product Label

(98075-5), then the marketing category is: ANADA (C73583), Conditional

NADA (C73588), NADA (C73593), Legally Marketed Unapproved New Animal

Drugs for Minor Species (C92556), Unapproved Homeopathic (C73614),

Unapproved Medical Gas (C73613), Unapproved Drug Other (C73627) or

Export Only (C73590).

3.2.9.3 If the marketing category is ANADA (C73583), Conditional NADA (C73588),

NADA (C73593), then the document type code is: OTC Animal Drug Label

(50577-6), OTC Type A Medicated Article Animal Drug Label (50576-8), OTC

Type B Medicated Feed Animal Drug Label (50574-3), OTC Type C Medicated

Feed Animal Drug Label (50573-5), Prescription Animal Drug Label (50578-4),

VFD Type A Medicated Article Animal Drug Label (50575-0), VFD Type B

Medicated Feed Animal Drug Label (50572-7), VFD Type C Medicated Feed

Animal Drug Label (50571-9), Recombinant Deoxyribonucleic Acid Construct

Label (78745-7), Intentional Animal Genomic Alteration Label (101437-2), or

Animal Cells, Tissues, and Cell and Tissue Based Product Label (98075-5).

SPL Implementation Guide with Validation Procedures v1

3.2.9.4 If the marketing category is Bulk Ingredient (C73626), Bulk Ingredient for

Human Prescription Compounding (C96793), or Bulk Ingredient for Animal

Drug Compounding (C98252), then the document type is Bulk Ingredient

(53409-9) or Bulk Ingredient – Animal drug (81203-2).

3.2.9.5 If the document type is Bulk Ingredient (53409-9), then the marketing category

is Bulk Ingredient (C73626), Bulk Ingredient for Human Prescription

Compounding (C96793), or Export Only (C73590).

3.2.9.6 If the code is ANDA (C73584), BLA (C73585), NDA (C73594), Approved Drug

Product Manufactured under Contract (C132333), NDA authorized generic

(C73605) , Multi-Market Approved Product (C175238), or SIP Approved Drug

(C175462) and the marketing status is active, then there exists a record of an

application for the application number, except if the document is an Indexing -

Product Concept (73815-3), Indexing - Warning Letter Alert (77288-9) or

Indexing – Risk Evaluation & Mitigation Strategies (82353-4).

3.2.9.7 If the code is ANDA (C73584), BLA (C73585), NDA (C73594), Approved Drug

Product Manufactured under Contract (C132333), NDA authorized generic

(C73605) , Multi-Market Approved Product (C175238), or SIP Approved Drug

(C175462) and the marketing is active with a start date on or before the current

date, then there exists a record of an approved application for the application

number.

3.2.9.8 If the code is ANDA (C73584), BLA (C73585), NDA (C73594), Approved Drug

Product Manufactured under Contract (C132333), NDA authorized generic

(C73605) , Multi-Market Approved Product (C175238), or SIP Approved Drug

(C175462) and the marketing status is completed, then there exists a record of

an approved or withdrawn application for the application number.

3.2.9.9 If the marketing category is Approved Drug Product Manufactured under

Contract (C132333), OTC Monograph Drug Product Manufactured Under

Contract (C132334), Unapproved Drug Product Manufactured Under Contract

(C132335), then the document type is Human Prescription Drug Label (34391-

3) or Human OTC Drug Label (34390-5).

3.2.9.10 If the marketing category is Medical Food (C86964), then the document type is

Medical Food (58475-5), except under parts.

3.2.9.11 If the document type is Medical Food (58475-5), then the marketing category is

Medical Food (C86964).

3.2.9.12 If the marketing category is Dietary Supplement (C86952), then the document

type is Dietary Supplement (58476-3), except under parts.

3 Product Data Elements

3.2.9.13 If the document type is Dietary Supplement (58476-3), then the marketing

category is Dietary Supplement (C86952).

3.2.9.14 If the document type is Human prescription drug label (34391-3), then the

marketing category is not OTC Monograph Drug Product Manufactured Under

Contract ( C132334), or OTC Monograph Drug (C200263) except under parts.

3.2.9.15 If the document type is Drug for Further Processing (78744-0), then the

marketing category is Drug for further processing (C94795) or Export Only

(C73590).

3.2.9.16 If the document type is Bulk ingredient - Animal drug (81203-2), then the

marketing category is Bulk Ingredient (C73626), (Bulk ingredient for animal

drug compounding (C98252), Drug for further processing (C94795) or Export

only (C73590).

3.2.9.17 If the document type is Human Compounded Drug Label (75031-5), then the

marketing category is Outsourcing Facility Compounded Human Drug Product

(Exempt From Approval Requirements) (C181659) or Outsourcing Facility

Compounded Human Drug Product (Not Marketed - Not Distributed)

(C190698).

3.2.9.18 If the document type is Animal Compounded Drug Label (77647-6), then the

marketing category is unapproved drug other (C73627).

3.2.9.19 If the marketing category is Emergency Use Authorization (C96966), then the

document type is Human Prescription Drug Label (34391-3) or Vaccine Label

(53404-0).

3.2.9.20 If the marketing category is Outsourcing Facility Compounded Human Drug

Product (Exempt From Approval Requirements) (C181659) or Outsourcing

Facility Compounded Human Drug Product (Not Marketed - Not Distributed)

(C190698), then the document type is Human Compounded Drug Label

(75031-5).

3.2.10 Marketing Status and Date

The procedures for marketing status and date (if any) are the same for all products

and described in Section 3.1.8.

Validation Procedures

3.2.10.1 There is one marketing status code for each top-level product (part products do

not need this), except if the document is a Indexing - Product Concept (73815-3)

or Lot Distribution Data (66105-8) or Indexing - Biologic or Drug Substance

(77648-4) or Human Compounded Drug Label (75031-5) or Animal

SPL Implementation Guide with Validation Procedures v1

Compounded Drug Label (77647-6) or Risk Evaluation & Mitigation Strategies

(82351-8) or Indexing – Risk Evaluation & Mitigation Strategies (82353-4) or if

the SPL file is for Salvaged Drugs (having business operation as salvage,

C70827).

3.2.11 DEA schedule

The DEA schedule, when applicable, is described under <policy> which is a child of

<subjectOf> which is a child of <manufacturedProduct> as illustrated in the

following example of a drug that is schedule II.

<code code="C48675"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="CII"/>

Validation Procedures

3.2.11.1 If the product item code (NDC) is on the DEA Exempt Products List, then there

is no DEA schedule.

3.2.11.2 There is only one DEA schedule element.

3.2.11.3 If there is a DEA schedule, then the code system is 2.16.840.1.113883.3.26.1.1

3.2.11.4 Display name matches the code

3.2.11.5 The policy element has a class code of ‘DEADrugSchedule’.

3.2.11.6 If the product item code (NDC) is not on the DEA Exempt Products List, then

the DEA Schedule matches the one in the Controlled Substance Table where all

supplied constraints match, except for products regulated by CVM.

3.2.11.7 If the product item code (NDC) is not on the DEA Exempt Products List and the

product's active ingredient(s) is in the Controlled Substance Table with DEA

Schedule CI, CII, CIII, CIV, or CV, and all supplied constraints matching, then

there is a DEA Schedule, except for products regulated by CVM.

3.2.12 Solid Oral Drug Product characteristics

Product characteristics include dosage form appearance. Dosage form characteristics

are used to describe the appearance of the drug product and include the color, score,

shape, size, imprint code and image. These are all under <subjectOf> which is a child

of <manufacturedProduct>. Product characteristics also include product flavor and

what the product contains.

3 Product Data Elements

<value code="code for color" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="display name for color" xsi:type="CE">

<originalText>optional original color description text</originalText>

</value>

</characteristic>

</subjectOf>

</characteristic>

</subjectOf>

<value code="code for shape" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="display name for shape" xsi:type="CE">

<originalText>optional original shape description text</originalText>

</value>

</characteristic>

</subjectOf>

</characteristic>

</subjectOf>

<value xsi:type="ST">imprint separated by semicolon</value>

</characteristic>

</subjectOf>

<value code="code for flavor" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="display name for flavor" xsi:type="CE">

<originalText>optional flavor description text</originalText>

</value>

</characteristic>

</subjectOf>

</value>

</characteristic>

</subjectOf>

3.2.13 Color

SPL Implementation Guide with Validation Procedures v1

<value code="C48333"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="blue" xsi:type="CE">

<originalText>LIGHT BLUE</originalText>

Validation Procedures

3.2.13.1 If the dosage form is on the solid oral dosage form list (see FDA SPL web page

for list https://www.fda.gov/industry/fda-resources-data-standards/structured-

product-labeling-resources), then there is a color, except if there is no marketing

status other than new or cancelled.

3.2.13.2 Code and code system is as above (for SPLCOLOR)

3.2.13.3 Value code system is 2.16.840.1.113883.3.26.1.1

3.2.13.4 Display name matches the value code

3.2.14 Shape

<value code="C48336"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="capsule" xsi:type="CE"/>

<originalText>capsule like</originalText>

Validation Procedures

3.2.14.1 If the dosage form is on the solid oral dosage form list (see FDA SPL web page

for list https://www.fda.gov/industry/fda-resources-data-standards/structured-

product-labeling-resources), then there is a shape, except if there is no marketing

status other than new or cancelled.

3.2.14.2 Code and code system is as above (for SPLSHAPE)

3.2.14.3 Value code system is 2.16.840.1.113883.3.26.1.1

3.2.14.4 Display name matches the value code

3.2.14.5 There is only one shape element

3.2.15 Size

3 Product Data Elements

Validation Procedures

3.2.15.1 If the dosage form is on the solid oral dosage form list (see FDA SPL web page

for list https://www.fda.gov/industry/fda-resources-data-standards/structured-

product-labeling-resources), then there is a size, except if there is no marketing

status other than new or cancelled.

3.2.15.2 Code and code system is as above (for SPLSIZE)

3.2.15.3 There is a unit and value for size element

3.2.15.4 Value units is mm for size element

3.2.15.5 Value is a whole number greater than zero for size element

3.2.15.6 There is only one size element

3.2.16 Scoring

Validation Procedures

3.2.16.1 If the dosage form is on the solid oral dosage form list (see FDA SPL web page

for list https://www.fda.gov/industry/fda-resources-data-standards/structured-

product-labeling-resources), then there is scoring, except if there is no marketing

status other than new or cancelled.

3.2.16.2 Code and code system is as above (for SPLSCORE)

3.2.16.3 The value is 1, 2, 3, 4 or nullFlavor=”OTH” (for SPLSCORE)

3.2.16.4 There is only one score element

3.2.17 Imprint code

SPL Implementation Guide with Validation Procedures v1

Validation Procedures

3.2.17.1 Code and code system is as above (for SPLIMPRINT)

3.2.17.2 Value has only letters and numbers separated by semicolon without spaces (for

SPLIMPRINT)

3.2.17.3 There is only one imprint code element

3.2.18 Flavor

<value code="C73391"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="grape" xsi:type="CE">

<originalText>wild grape</originalText>

Validation Procedures

3.2.18.1 If there is a flavor, then code and code system is as above

3.2.18.2 Value code system is 2.16.840.1.113883.3.26.1.1

3.2.18.3 Display name matches the value code

3.2.19 Image for Solid Oral Dosage Forms

Validation Procedures

3.2.19.1 If there is SPL image of the solid oral dosage form, then code and code system

are as above

3.2.19.2 Value xsi:type is as above

3.2.19.3 mediaType is “image/jpeg”

3.2.19.4 Reference value is the file name for a valid image

3.2.19.5 The image file is submitted together with the SPL file.

3.2.19.6 There are no product characteristics other than the ones mentioned above.

3 Product Data Elements

3.2.20 Route of administration

Route of administration may be specified for products

and their parts:

<part>

Route of administration is specified as follows:

<routeCode code="C38288"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="oral"/>

Validation Procedures

3.2.20.1 If the document type is not for Bulk Ingredient (53409-9), Bulk Ingredient –

Animal Drug (81203-2), Licensed Vaccine Bulk Intermediate Label (53406-5) or

Drug for Further Processing (78744-0) and product is not a top-level product

whose form code is Kit (C47916) or there is no marketing status other than new

or cancelled, then there is one or more route of administration

(consumedIn/substanceAdministration element with routeCode), except if the

document type is Indexing - Product Concept (73815-3) or Lot Distribution

Data (66105-8) or Indexing - Biologic or Drug Substance (77648-4) or Risk

Evaluation & Mitigation Strategies (82351-8) or Indexing – Risk Evaluation &

Mitigation Strategies (82353-4) or if the SPL file is for Salvaged Drugs, i.e.,

having business operation as salvage (C70827).

3.2.20.2 Route code system is 2.16.840.1.113883.3.26.1.1

3.2.20.3 There is a display name that matches the code

3.2.20.4 If the document type is for Bulk Ingredient (53409-9), Bulk Ingredient – Animal

Drug (81203-2), Licensed Vaccine Bulk Intermediate Label (53406-5) or Drug

for Further Processing (78744-0) then route code is not applicable (nullFlavor

NA) or not present at all.

3.2.20.5 The route (of administration) code cannot be “not applicable” (C48623) for

document types other than Bulk Ingredient (53409-9), Bulk Ingredient – Animal

Drug (81203-2), Licensed Vaccine Bulk Intermediate Label (53406-5) ,

SPL Implementation Guide with Validation Procedures v1

Recombinant Deoxyribonucleic Acid Construct Label (78745-7), Intentional

Animal Genomic Alteration Label (101437-2), or Drug for Further Processing

(78744-0).

3.3 Device Product

<name>SuperTape 2000</name>

<desc>Adhesive tape for orthopedic use.</desc>

<code code="MCA" displayName="Tape, Surgical, Internal"

codeSystem="2.16.840.1.113883.6.303"/>

</generalizedMaterialKind>

</asSpecializedKind>

Device products are those products with the appropriate marketing categories listed in

Table 1: Marketing Category and Product Type.

3.3.1 Item Code and Name

Validation Procedures

3.3.1.1 There may be an NDC product/item code

3.3.1.2 If there is a NDC product/item code, the following general procedures apply:

3.3.1.3 Code system is 2.16.840.1.113883.6.69 (NHRIC), 1.3.160(GS1), or

2.16.840.1.113883.6.40 (HIBCC).

3.3.1.4 Code is compliant with the code system’s allocation rules.

3.3.1.5 There is a name, i.e., the trade or proprietary name of the medical device as used

in product labeling or in the catalog

3.3.1.6 Markings such as ®, or ™ should not be included

3.3.1.7 There is a device type (asSpecializedKind element) with a code.

3.3.1.8 code system is 2.16.840.1.113883.6.303 for FDA Product Classification System

3.3.1.9 there is a valid medical device product classification code

3.3.1.10 there is a displayName which matches the code

3 Product Data Elements

3.3.2 Additional Device Identifiers

<code code="C99286" displayName="model number"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

</asIdentifiedEntity>

These additional identifiers may also appear under device parts:

<part>

3.3.2.1 There may be one or more additional identifiers, including model number

(C99286), catalog number (C99285), and reference number (C99287).

3.3.2.2 There is a code with code system 2.16.840.1.113883.3.26.1.1.

3.3.2.3 Code is from the Table 3: Miscellaneous Identifier Types.

3.3.2.4 There is one id

3.3.2.5 Id has a root OID

3.3.2.6 The actual identifier is in the extension.

3.3.2.7 There is at most one Model Number reference (C99286)

3.3.2.8 The id root can be any root OID over which the labeler has authority. If the

labeler has no such root OID of its own, then the root is constructed by

concatenating the DUNS number (without leading zeroes) to the fixed string

“1.3.6.1.4.1.32366.3.”

3.3.2.9 There is at most one Catalog Number (C99285)

3.3.2.10 The id root can be any root OID over which the labeler has authority. If the

labeler has no such root OID of its own, then the root is constructed by

concatenating the DUNS number (without leading zeroes) to the fixed string

“1.3.6.1.4.1.32366.3.”

3.3.2.11 The product may have multiple reference numbers (i.e., secondary identifiers,

C99287).

SPL Implementation Guide with Validation Procedures v1

3.3.2.12 The id root is 2.16.840.1.113883.6.69 (NHRIC), 1.3.160 (GS1),

2.16.840.1.113883.6.40 (HIBCC), or may be constructed by concatenating the

DUNS number (without leading zeroes) to the fixed string

“1.3.6.1.4.1.32366.3.”

3.3.2.13 Id extension is compliant with the code system’s allocation rules.

3.3.3 [RESERVED]

3.3.4 Device Ingredient

Ingredients included in devices that are not identified as active ingredients include the

ingredient class code, ingredient name, identifier, and strength. The element

<ingredient> is a child of <manufacturedProduct>. The class code for ingredient is

“INGR”. The strength, if needed, is represented as a numerator and denominator and

is described using UCUM units of measure.

</quantity>

<name>ingredient name</name>

</ingredientSubstance>

</ingredient>

This structure is also used to indicate that a product contains latex (UNII code for

latex).

Note that devices may have active ingredients as well, such as in a medicated stent,

i.e., where the device serves in part the function of releasing a built-in drug. This is to

be distinguished from devices such as syringes which are delivery devices for a drug

product that they contain.

3.3.5 [RESERVED]

3.3.6 [RESERVED]

3.3.7 Device Parts

Device parts may be specified for the product in the same way as for other product

kits (see Section 3.1.6 Kits, Parts, Components and Accessories above),

3 Product Data Elements

<name>SuperTape 2000</name>

<code code="MCA"

codeSystem="2.16.840.1.113883.6.303"/>

</generalizedMaterialKind>

</asSpecializedKind>

Validation Procedures

3.3.7.1 There is a name, i.e., the trade or proprietary name of the medical device as used

in product labeling or in the catalog

3.3.7.2 Markings such as ®, or ™ should not be included

3.3.8 Part of Assembly

When products are used together but packaged separately, the data element

<asPartOfAssembly> is used to identify the other product. The products could be

drugs or devices.

<part>

<code code="item code of accessory component"

codeSystem="code system OID"/>

3.3.9 Regulatory Identifiers

Regulatory identifiers, marketing status and characteristics are all connected through

the <subjectOf> element which may appear on the main product:

The regulatory identifier:

<code code="C80442"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="Premarket Notification"/>

SPL Implementation Guide with Validation Procedures v1

Validation Procedures

3.3.9.1 There is one regulatory identifier for each product

3.3.9.2 Code comes from Table 1 for product type “device”.

3.3.9.3 Display name matches the code

3.3.9.4 Code system is 2.16.840.1.113883.3.26.1.1

3.3.9.5 If the marketing category (code) is Premarket Application (C80441), 510(k)

Premarket Notification (C80442), Exempt Device (C80438), or Humanitarian

Device Exemption (C80440), then the id root is 2.16.840.1.113883.3.150.

3.3.9.6 If the marketing category (code) is Premarket Application (C80441), then the id

extension has a prefix “P” or “BP” followed by 6 digits

3.3.9.7 If the marketing category (code) is Premarket Notification (C80442), then the id

extension has a prefix “K” or “BK” followed by 6 digits.

3.3.9.8 If the marketing category (code) is Exempt Device (C80438), then the id

extension consists of 3 letters

3.3.9.9 If the marketing category (code) is Humanitarian Device Exemption (C80440),

then the id extension has a prefix “H” followed by 6 digits

3.3.9.10 Territorial authority is as above

3.3.9.11 If the form code is kit (C47916) and the top/kit-level marketing category is

Exempt device (C80438), Humanitarian Device Exemption (C80440),

Premarket Application (C80441) or Premarket Notification (C80442), then the

document type is not Bulk Ingredient (53409-9), Cellular Therapy (60684-8),

Drug for Further Processing (78744-0), Human OTC Drug Label (34390-5),

Human Prescription Drug Label (34391-3), License Blood Intermediates/Paste

Label (53407-3), Licensed Minimally Manipulated Cells Label (53408-1),

Licensed Vaccine Bulk Intermediate Label (53406-5), Non-Standardized

Allergenic Label (53405-7), OTC Type A Medicated Article Animal Drug Label

(50576-8), OTC Type C Medicated Feed Animal Drug Label (50573-5), Plasma

Derivative (60683-0), Prescription Animal Drug Label (50578-4), Standardized

Allergenic (60682-2), Vaccine Label (53404-0), Animal Cells, Tissues, and Cell

and Tissue Based Product Label (98075-5), OTC Animal Drug Label (50577-6),

Recombinant Deoxyribonucleic Acid Construct Label (78745-7), Intentional

Animal Genomic Alteration Label (101437-2), VFD Type A Medicated Article

Animal Drug Label (50575-0), VFD Type B Medicated Feed Animal Drug Label

(50572-7), VFD Type C Medicated Feed Animal Drug Label (50571-9), Animal

3 Product Data Elements

Compounded Drug Label (77647-6), Bulk Ingredient - Animal Drug (81203-2),

or Human Compounded Drug Label (75031-5).

3.3.9.12 If the form code is not kit (C47916) and the document type is Bulk Ingredient

(53409-9), Cellular Therapy (60684-8), Drug for Further Processing (78744-0),

Human OTC Drug Label (34390-5), Human Prescription Drug Label (34391-3),

License Blood Intermediates/Paste? Label (53407-3), Licensed Minimally

Manipulated Cells Label (53408-1), Licensed Vaccine Bulk Intermediate Label

(53406-5), Non-Standardized Allergenic Label (53405-7), OTC Type A

Medicated Animal Drug Label (50576-8), OTC Type C Medicated Feed Animal

Drug Label (50573-5), Plasma Derivative (60683-0), Prescription Animal Drug

Label (50578-4), Standardized Allergenic (60682-2), or Vaccine Label (53404-

0), Animal Cells, Tissues, and Cell and Tissue Based Product Label (98075-5),

OTC Animal Drug Label (50577-6), Recombinant Deoxyribonucleic Acid

Construct Label (78745-7), Intentional Animal Genomic Alteration Label

(101437-2), VFD Type A Medicated Article Animal Drug Label (50575-0), VFD

Type B Medicated Feed Animal Drug Label (50572-7), VFD Type C Medicated

Feed Animal Drug Label (50571-9), Animal Compounded Drug Label (77647-

6), Bulk Ingredient - Animal Drug (81203-2), or Human Compounded Drug

Label (75031-5), then the marketing category is not Exempt device (C80438),

Humanitarian Device Exemption (C80440), Premarket Application (C80441) or

Premarket Notification (C80442).

3.3.10 Marketing status and date

The procedures for marketing status and date (if any) are the same for all products

and described in Section 3.1.8.

Validation Procedures

3.3.10.1 There is one marketing status code for each top-level product (part products do

not need this)

3.3.11 Device Characteristics

Many characteristics exist for devices and are listed here in tabular form. The

characteristic structure allows specifying any properties of the product in a code-

value pair, the code saying which property is being specified, the value saying what

the property is for the given product. The characteristics structure connects to the

product Role through the subjectOf element.

...

</manufacturedProduct>

SPL Implementation Guide with Validation Procedures v1

<code code="characteristic code"

codeSystem="characteristic code system"/>

Characteristics listed in Table 6 use one of a number of different data types. Each data

type uses slightly different XML elements and attributes as shown in the templates in

Section 3.1.8.34

Table 6: Characteristic codes and code systems.

Name Code / Code System OID Data

Type

Description

Number of times

useable.

SPLUSE

2.16.840.1.113883.1.11.19255

INT Specifies how often a product may be re-

used. While a number could be specified,

the common distinction is between single

disposable and multiple use products. A

product that has unlimited reuses uses the

<value nullFlavor=”PINF” xsi:type=”INT”/>.

Sterile Use SPLSTERILEUSE

2.16.840.1.113883.1.11.19255

BL Specifies whether the device is intended or

not intended to be used where sterile

conditions are necessary (e.g., pens).

MRI Safety SPLMRISAFE

2.16.840.1.113883.1.11.19255

BL Yes (MRI Safe), No (MRI unsafe)

Validation Procedures

3.3.11.1 There are no device characteristics other than the ones mentioned in this

document.

3.3.12 Reusability

Unlimited reusability is represented as follows:

<value nullFlavor=“PINF” xsi:type=“INT”/>.

Validation Procedures

3.3.12.1 Code and code system is as above

3.3.12.2 The value is an integer number greater or equal 1 (1 meaning single use, and

number greater than 1 meaning reusable up to this many times) or there is

nullFlavor “PINF” and no value.

3 Product Data Elements

3.3.12.3 There is only one reusability element

3.3.13 [RESERVED]

3.3.14 Sterile Use

<code code="SPLSTERILEUSE"

codeSystem="2.16.840.1.113883.1.11.19255"/>

Validation Procedures

3.3.14.1 Code and code system are as above

3.3.14.2 Value type is “BL” (Boolean)

3.3.14.3 Value is “true” or “false”

3.4 Cosmetic Product

Cosmetic products are those products with marketing category C86965 (cosmetic) or

any product inside a document of type Cosmetic Product Listing (103572-4), or

Cosmetic Facility Registration (103573-2), Cosmetic Facility Registration –

Amendment (X8888-1), or Cosmetic – Update (X8888-5).

3.4.1 Cosmetic Product Item Code

<name>Juvenia Soft</name>

Validation Procedures

3.4.1.1 If the document is a Cosmetic Product Listing, then the item code is a cosmetic

product listing number (see Section 36.2.2.1 and following).

3.4.1.2 If the document is not a Cosmetic Product Listing or Cosmetic Facility

Registration, then the item code should be a GS1 GTIN.

3.4.1.3 If the document is a Cosmetic Facility Registration, then there is no item code.

3.4.2 Cosmetic Product Name

The product name is the statement of identity, as such name appears on the label. If

the product names in the listing are not unique, then also include distinguishing

information for identification purposes, for example brand name or a code that the

SPL Implementation Guide with Validation Procedures v1

responsible person uses to distinguish the product. Such information may also be

included in addition to the product name even when product names in the listing are

unique. If you believe certain distinguishing information is confidential, include that

distinguishing information in parenthesis.

<name>Juvenia Soft</name>

Validation Procedures

3.4.2.1 There is a name, i.e., the product name of the cosmetic as used in product

labeling or in the catalog.

3.4.2.2 Markings such as ®, or ™ should not be included

3.4.3 Cosmetic Product Category

<code code="01B" displayName="lotions, oils, powders, and creams"

codeSystem="2.16.840.1.113883.6.303"/>

</generalizedMaterialKind>

</asSpecializedKind>

3.4.3.1 There are one or more cosmetic product category codes (asSpecializedKind

element) with a code.

3.4.3.2 code system is 2.16.840.1.113883.6.303 for FDA Product Classification System

3.4.3.3 there is a valid cosmetic product category code

3.4.3.4 there is a displayName which matches the code

3.4.3.5 If one cosmetic product category code is “Other baby products, leave-on [Baby

products]” (01D1), then another cannot be “Other baby products, rinse-off

[Baby products]” (01D2), except if the document type is Cosmetic Facility

Registration (103573-2), Cosmetic Facility Registration - Amendment (X8888-

1) and Cosmetic Facility Registration - Biennial Renewal (X8888-4).

3.4.3.6 If one cosmetic product category code is “Other baby products, rinse-off [Baby

products]” (01D2), then another cannot be “Other baby products, leave-on

[Baby products]” (01D1), except if the document type is Cosmetic Facility

Registration (103573-2), Cosmetic Facility Registration - Amendment (X8888-

1) and Cosmetic Facility Registration - Biennial Renewal (X8888-4).

3 Product Data Elements

3.4.3.7 If one cosmetic product category code is “Shampoos (non-coloring), leave-on

[Hair preparations (non-coloring)]” (06F1), then another cannot be “Shampoos

(non-coloring), rinse-off [Hair preparations (non-coloring)]” (06F2), except if

the document type is Cosmetic Facility Registration (103573-2), Cosmetic

Facility Registration - Amendment (X8888-1) and Cosmetic Facility

Registration - Biennial Renewal (X8888-4).

3.4.3.8 If one cosmetic product category code is “Shampoos (non-coloring), rinse-off

[Hair preparations (non-coloring)]” (06F2), then another cannot be “Shampoos

(non-coloring), leave-on [Hair preparations (non-coloring)]” (06F1), except if

the document type is Cosmetic Facility Registration (103573-2), Cosmetic

Facility Registration - Amendment (X8888-1) and Cosmetic Facility

Registration - Biennial Renewal (X8888-4).

3.4.3.9 If one cosmetic product category code is “Other hair preparations, leave-on

[Hair preparations (non-coloring)]” (06I1), then another cannot be “Other hair

preparations, rinse-off [Hair preparations (non-coloring)]” (06I2), except if the

document type is Cosmetic Facility Registration (103573-2), Cosmetic Facility

Registration - Amendment (X8888-1) and Cosmetic Facility Registration -

Biennial Renewal (X8888-4).

3.4.3.10 If one cosmetic product category code is “Other hair preparations, rinse-off

[Hair preparations (non-coloring)]” (06I2), then another cannot be “Other hair

preparations, leave-on [Hair preparations (non-coloring)]” (06I1), except if the

document type is Cosmetic Facility Registration (103573-2), Cosmetic Facility

Registration - Amendment (X8888-1) and Cosmetic Facility Registration -

Biennial Renewal (X8888-4).

3.4.3.11 If one cosmetic product category code is “Hair rinses (coloring), leave-on [Hair

coloring preparations]” (07C1), then another cannot be “Hair rinses (coloring),

rinse-off [Hair coloring preparations]” (07C2), except if the document type is

Cosmetic Facility Registration (103573-2), Cosmetic Facility Registration -

Amendment (X8888-1) and Cosmetic Facility Registration - Biennial Renewal

(X8888-4).

3.4.3.12 If one cosmetic product category code is “Hair rinses (coloring), rinse-off [Hair

coloring preparations]” (07C2), then another cannot be “Hair rinses (coloring),

leave-on [Hair coloring preparations]” (07C1), except if the document type is

Cosmetic Facility Registration (103573-2), Cosmetic Facility Registration -

Amendment (X8888-1) and Cosmetic Facility Registration - Biennial Renewal

(X8888-4).

3.4.3.13 If one cosmetic product category code is “Hair shampoos (coloring), leave-on

[Hair coloring preparations]” (07D1), then another cannot be “Hair shampoos

(coloring), rinse-off [Hair coloring preparations]” (07D2), except if the

document type is Cosmetic Facility Registration (103573-2), Cosmetic Facility

SPL Implementation Guide with Validation Procedures v1

Registration - Amendment (X8888-1) and Cosmetic Facility Registration -

Biennial Renewal (X8888-4).

3.4.3.14 If one cosmetic product category code is “Hair shampoos (coloring), rinse-off

[Hair coloring preparations]” (07D2), then another cannot be “Hair shampoos

(coloring), leave-on [Hair coloring preparations]” (07D1), except if the

document type is Cosmetic Facility Registration (103573-2), Cosmetic Facility

Registration - Amendment (X8888-1) and Cosmetic Facility Registration -

Biennial Renewal (X8888-4).

3.4.3.15 If one cosmetic product category code is “Other hair coloring preparations,

leave-on [Hair coloring preparations]” (07I1), then another cannot be “Other

hair coloring preparations, rinse-off [Hair coloring preparations]” (07I2), except

if the document type is Cosmetic Facility Registration (103573-2), Cosmetic

Facility Registration - Amendment (X8888-1) and Cosmetic Facility

Registration - Biennial Renewal (X8888-4).

3.4.3.16 If one cosmetic product category code is “Other hair coloring preparations,

rinse-off [Hair coloring preparations]” (07I2), then another cannot be “Other

hair coloring preparations, leave-on [Hair coloring preparations]” (07I1), except

if the document type is Cosmetic Facility Registration (103573-2), Cosmetic

Facility Registration - Amendment (X8888-1) and Cosmetic Facility

Registration - Biennial Renewal (X8888-4).

3.4.3.17 If one cosmetic product category code is “Feminine deodorants, leave-on

[Personal cleanliness]” (12D1), then another cannot be “Feminine deodorants,

rinse-off [Personal cleanliness]” (12D2), except if the document type is

Cosmetic Facility Registration (103573-2), Cosmetic Facility Registration -

Amendment (X8888-1) and Cosmetic Facility Registration - Biennial Renewal

(X8888-4).

3.4.3.18 If one cosmetic product category code is “Feminine deodorants, rinse-off

[Personal cleanliness]” (12D2), then another cannot be “Feminine deodorants,

leave-on [Personal cleanliness]” (12D1), except if the document type is

Cosmetic Facility Registration (103573-2), Cosmetic Facility Registration -

Amendment (X8888-1) and Cosmetic Facility Registration - Biennial Renewal

(X8888-4).

3.4.3.19 [RESERVED].

3.4.3.20 If one cosmetic product category code is “Other personal cleanliness products,

leave-on [Personal cleanliness]” (12F1), then another cannot be “Other personal

cleanliness products, rinse-off [Personal cleanliness]” (12F2), except if the

document type is Cosmetic Facility Registration (103573-2), Cosmetic Facility

Registration - Amendment (X8888-1) and Cosmetic Facility Registration -

Biennial Renewal (X8888-4).

3 Product Data Elements

100

3.4.3.21 [RESERVED].

3.4.3.22 If one cosmetic product category code is “Other personal cleanliness products,

rinse-off [Personal cleanliness]” (12F2), then another cannot be “Other personal

cleanliness products, leave-on [Personal cleanliness]” (12F1), except if the

document type is Cosmetic Facility Registration (103573-2), Cosmetic Facility

Registration - Amendment (X8888-1) and Cosmetic Facility Registration -

Biennial Renewal (X8888-4).

3.4.3.23 If one cosmetic product category code is “Face and neck (excluding shaving

preparations), leave-on [Skin care preparations (creams, lotions, powder, and

sprays)]” (14C1), then another cannot be “Face and neck (excluding shaving

preparations), rinse-off [Skin care preparations (creams, lotions, powder, and

sprays)]” (14C2), except if the document type is Cosmetic Facility Registration

(103573-2), Cosmetic Facility Registration - Amendment (X8888-1) and

Cosmetic Facility Registration - Biennial Renewal (X8888-4).

3.4.3.24 If one cosmetic product category code is “Face and neck (excluding shaving

preparations), rinse-off [Skin care preparations (creams, lotions, powder, and

sprays)]” (14C2), then another cannot be “Face and neck (excluding shaving

preparations), leave-on [Skin care preparations (creams, lotions, powder, and

sprays)]” (14C1), except if the document type is Cosmetic Facility Registration

(103573-2), Cosmetic Facility Registration - Amendment (X8888-1) and

Cosmetic Facility Registration - Biennial Renewal (X8888-4).

3.4.3.25 If one cosmetic product category code is “Body and hand (excluding shaving

preparations), leave-on [Skin care preparations (creams, lotions, powder, and

sprays)]” (14D1), then another cannot be “Body and hand (excluding shaving

preparations), rinse-off [Skin care preparations (creams, lotions, powder, and

sprays)]” (14D2), except if the document type is Cosmetic Facility Registration

(103573-2), Cosmetic Facility Registration - Amendment (X8888-1) and

Cosmetic Facility Registration - Biennial Renewal (X8888-4).

3.4.3.26 If one cosmetic product category code is “Body and hand (excluding shaving

preparations), rinse-off [Skin care preparations (creams, lotions, powder, and

sprays)]” (14D2), then another cannot be “Body and hand (excluding shaving

preparations), leave-on [Skin care preparations (creams, lotions, powder, and

sprays)]” (14D1), except if the document type is Cosmetic Facility Registration

(103573-2), Cosmetic Facility Registration - Amendment (X8888-1) and

Cosmetic Facility Registration - Biennial Renewal (X8888-4).

3.4.3.27 If one cosmetic product category code is “Other skin care preparations, leave-on

[Skin care preparations (creams, lotions, powder, and sprays)]” (14J1), then

another cannot be “Other skin care preparations, rinse-off [Skin care

preparations (creams, lotions, powder, and sprays)]” (14J2), except if the

document type is Cosmetic Facility Registration (103573-2), Cosmetic Facility

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101

Registration - Amendment (X8888-1) and Cosmetic Facility Registration -

Biennial Renewal (X8888-4).

3.4.3.28 If one cosmetic product category code is “Other skin care preparations, rinse-off

[Skin care preparations (creams, lotions, powder, and sprays)]” (14J2), then

another cannot be “Other skin care preparations, leave-on [Skin care

preparations (creams, lotions, powder, and sprays)]” (14J1), except if the

document type is Cosmetic Facility Registration (103573-2), Cosmetic Facility

Registration - Amendment (X8888-1) and Cosmetic Facility Registration -

Biennial Renewal (X8888-4).

3.4.3.29 If one cosmetic product category code is “Hair Conditioners (non-coloring),

leave-on [Hair preparations]” (06A1), then another cannot be “Hair Conditioners

(non-coloring), rinse-off [Hair preparations]” (06A2), except if the document

type is Cosmetic Facility Registration (103573-2), Cosmetic Facility

Registration - Amendment (X8888-1) and Cosmetic Facility Registration -

Biennial Renewal (X8888-4).

3.4.3.30 If one cosmetic product category code is “Hair Conditioners (non-coloring),

rinse-off [Hair preparations]” (06A2), then another cannot be “Hair Conditioners

(non-coloring), leave-on [Hair preparations]” (06A1), except if the document

type is Cosmetic Facility Registration (103573-2), Cosmetic Facility

Registration - Amendment (X8888-1) and Cosmetic Facility Registration -

Biennial Renewal (X8888-4).

3.4.4 Cosmetic Ingredient

Cosmetic ingredients use the class code INGR, or COLR for color additives. The

ingredients are included in the order as in the label, i.e., generally descending order of

predominance, with an alternative grouping as per 21 CFR 701.3(f).

<name>ingredient name</name>

</ingredientSubstance>

</ingredient>

Validation Procedures

3.4.4.1 Class code for cosmetic ingredients is INGR or COLR

3.4.4.2 [RESERVED]

3.4.4.3 [RESERVED]

3.4.4.4 If the document type is one of the Cosmetic Facility Registrations (see Section

35), then there are no ingredients.

3 Product Data Elements

102

3.4.4.5 For cosmetics the ingredient substance (UNII) code is optional.

3.4.4.6 There may be one ingredient specified as flavor(s) by ingredient name simply

“flavor” or “flavors” without a UNII code.

<name>flavors</name>

</ingredientSubstance>

</ingredient>

3.4.4.7 There may be one ingredient specified as fragrance(s) by ingredient name

simply “fragrance” or “fragrances” without a UNII code.

<name>fragrances</name>

</ingredientSubstance>

</ingredient>

3.4.4.8 Cosmetic Product Listing documents (see Section 36) have no ingredient

quantity.

3.4.5 Cosmetic Parts

Cosmetic parts may be specified for the product in the same way as for other product

kits (see Section 3.1.6 Kits, Parts, Components and Accessories above),

<name>Juvenia Soft</name>

<code code="MCA"

codeSystem="2.16.840.1.113883.6.303"/>

</generalizedMaterialKind>

</asSpecializedKind>

Note that in cosmetic product listing (Section 36) kits with parts are currently not

expected.

Validation Procedures

3.4.5.1 There is a name, i.e., the trade or proprietary name of the cosmetic as used in

product labeling or in the catalog

3.4.5.2 Markings such as ®, or ™ should not be included

SPL Implementation Guide with Validation Procedures v1

103

3.4.6 Marketing status and date

The procedures for marketing status and date (if any) are the same for all products

and described in Section 3.1.8, except that products listed in cosmetic product listing

documents do not require a marketing status unless discontinued.

Validation Procedures

3.4.6.1 There is one marketing status code for each top-level product (part products do

not need this), except if the document is a cosmetic product listing or cosmetics

facility registration.

3.4.6.2 If the document is a cosmetics facility registration, then there is no marketing

status.

3.4.6.3 If the document is a cosmetic product listing and the product is to be

discontinued, then there is a marketing status code of “completed”.

3.4.7 Product Web Page Link

Web page to the product may be provided with an absolute URL reference with the

“http://” or https://” protocol as follows:

<text>

</text>

</document>

Validation Procedures

3.4.7.1 Web page reference has a text element with reference (text reference) but no

mediaType.

3.4.7.2 Text reference value is an absolute URL, starting with a URL scheme “http://”

or “https://”.

3.4.7.3 There are no elements other than text.

3.4.8 Professional Use

To indicate that the cosmetic product is intended for use by professionals only,

include the following characteristic:

...

3 Product Data Elements

104

<code code="SPLPROFESSIONALUSE"

codeSystem="2.16.840.1.113883.1.11.19255"/>

</characteristic>

</subjectOf>

3.4.8.1 Code and code system is as above (“SPLPROFESSIONALUSE”)

3.4.8.2 There is a Boolean value is “true”.

3.4.8.3 Value may be “true” (professional use); to indicate general use, omit this

property.

3.4.9 Image of Label for Cosmetics

Validation Procedures

3.4.9.1 There may be one or more images of labels with the characteristic code and code

system are as above.

3.4.9.2 Value xsi:type is as above

3.4.9.3 mediaType is “image/jpeg”

3.4.9.4 Reference value is the file name for a valid image

3.4.9.5 The image file is submitted together with the SPL file.

3.4.9.6 There are no product characteristics other than the ones mentioned above.

3.5 Summary of Product Data Elements

This concludes the specific data elements recognized about various types of products.

The following sections describe specific business processes which may or may not

contain the above product data element structures.

Validation Procedures

3.5.1.1 There are no products or parts that do not follow the validation procedures for

the major types described in this section, except if there is no marketing status

other than new or cancelled.

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105

4 Drug and Biologics Labeling, Listing, and other Product

Submissions

Drug labeling provides a description of the product and information for its use. Drug

listing links registered establishments to specific products.

4.1 Header

4.1.1 Document Type

4.1.1.1 Document types for labeling and listing are in the following Table 7. Some

validation procedures vary by which FDA Center has authority over the types of

products submitted with the respective document.

Table 7: Document Types for Labeling , Listing, and other Product Submissions

Code

Display Name

FDA Center

53409-9

BULK INGREDIENT

CDER

81203-2

BULK INGREDIENT – ANIMAL DRUG

CVM

60684-8

CELLULAR THERAPY

CBER

58474-8

COSMETIC

CFSAN

103572-4

COSMETIC PRODUCT LISTING

CFSAN

58476-3

DIETARY SUPPLEMENT

CFSAN

34390-5

HUMAN OTC DRUG LABEL

CDER

34391-3 HUMAN PRESCRIPTION DRUG LABEL, except if the

application number prefix is “BN” or “BA”

CDER

34391-3

HUMAN PRESCRIPTION DRUG LABEL if the application

number prefix is “BN” or “BA”

CBER

75031-5

HUMAN COMPOUDED DRUG LABEL

CDER

101437-2

INTENTIONAL ANIMAL GENOMIC ALTERATION LABEL

CVM

53407-3

LICENSE BLOOD INTERMEDIATES/PASTE LABEL

CBER

53408-1

LICENSED MINIMALLY MANIPULATED CELLS LABEL

CBER

53406-5

LICENSED VACCINE BULK INTERMEDIATE LABEL

CBER

55439-4

MEDICAL DEVICE

CDRH

58475-5

MEDICAL FOOD

CFSAN

53405-7

NON-STANDARDIZED ALLERGENIC LABEL

CBER

50577-6

OTC ANIMAL DRUG LABEL

CVM

69403-4

OTC MEDICAL DEVICE LABEL

CDRH

50576-8

OTC TYPE A MEDICATED ARTICLE ANIMAL DRUG LABEL

CVM

50574-3

OTC TYPE B MEDICATED FEED ANIMAL DRUG LABEL

CVM

50573-5

OTC TYPE C MEDICATED FEED ANIMAL DRUG LABEL

CVM

60683-0

PLASMA DERIVATIVE

CBER

50578-4

PRESCRIPTION ANIMAL DRUG LABEL

CVM

69404-2

PRESCRIPTION MEDICAL DEVICE LABEL

CDRH

60682-2

STANDARDIZED ALLERGENIC

CBER

53404-0

VACCINE LABEL

CBER

50575-0

VFD TYPE A MEDICATED ARTICLE ANIMAL DRUG LABEL

CVM

50572-7

VFD TYPE B MEDICATED FEED ANIMAL DRUG LABEL

CVM

50571-9

VFD TYPE C MEDICATED FEED ANIMAL DRUG LABEL

CVM

4 Drug and Biologics Labeling, Listing, and

other Product Submission

106

78745-7

RECOMBINANT DEOXYRIBONUCLEIC ACID

CVM

77647-6

ANIMAL COMPOUNDED DRUG

CVM

78744-0

DRUG FOR FURTHER PROCESSING

CDER

98075-5 ANIMAL CELLS, TISSUES, AND CELL AND TISSUE BASED

PRODUCT LABEL

CVM

4.1.1.2 If a document with the same set id has been previously submitted, then it is of

the same type, except if the previous document type was Bulk Ingredient

(53409-9) or Bulk ingredient – Animal drug (81203-2) and the present document

type is Drug for Further Processing (78744-0).

4.1.1.3 If any active ingredient code is on the list of active ingredients approved for

vaccines, then the document type code is Vaccine Label (53404-0) or Licensed

Vaccine Bulk Intermediate Label (53406-5), except if the strength unit is a

homeopathic unit.

4.1.1.4 If the document type changes from Human Prescription Drug Label (34391-3)

to Human OTC Drug Label (34390-5), then submit a new listing file with new

NDC product codes for the OTC drug.

4.1.2 Labeler information

<code code="..." codeSystem="2.16.840.1.113883.6.1"

displayName="..."/>

<name>Acme drug company</name>

Validation Procedures

4.1.2.1 There is one labeler.

4.1.2.2 There is one id, the labeler’s DUNS number, and name is as in Section 2.1.5.

4.1.2.3 The set id is not associated with any top level product with a different NDC

Labeler Prefix

4.1.2.4 There is no other element besides id (the labeler’s DUNS Number), name and

registrant.

4.1.3 Registrant information

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<name>Acme drug company</name>

Validation Procedures

4.1.3.1 There may be registrant information

4.1.3.2 If there is a registrant, then there is one id, (the registrants DUNS number) and a

name as in Section 2.1.5.

4.1.3.3 There is no other element besides registrant’s id, registrant’s name and

establishments.

4.1.3.4 There is not more than one registrant element.

4.1.4 Establishment information

<name>Middleton Manufacturing company</name>

</assignedOrganization>

<code code="C43360"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="manufacture"/>

Validation Procedures

4.1.4.1 If the marketing status code for any of the products that is or includes a drug is

active, then there are one or more establishments.

4.1.4.2 There is one id (the DUNS number) and name is as in Section 2.1.5.

4.1.4.3 Id (DUNS Number) is not used for other establishments in the file

4.1.4.4 Establishment (“assignedOrganization”) has no other element besides id (the

DUNS Number) and name.

Drug and Biologics Labeling, Listing, and other Product Submission

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4.1.4.5 The establishment id (DUNS Number) has been submitted in a document of type

Establishment Registration (51725-0) on or after October 1st of the previous

year, or, if earlier, that Establishment Registration has been followed by a

document of type No Change Notification (53410-7) between October 1st and

December 31st of the previous or the current year, and that has not been

inactivated by an FDA Agency Initiated Compliance Action, except if all

products have the marketing status completed.

4.1.4.6 There are one or more business operations.

4.1.4.7 Business operation name (act definition code display name) matches

corresponding business operation code

4.1.4.8 The code comes from the business operations list except for Import (C73599),

United States Agent (C73330), Distributes Drug Products under own Private

Label (C73608), API/FDF Analytical Testing (C101509), Clinical

Bioequivalence or Bioavailability Study (C101511), FDF Manufacture

(C101510), In Vitro Bioequivalence or Bioanalytical Testing (C101512),

Wholesale Drug Distributor (C118411), and Third-Party Logistics Provider

(C118412).

4.1.4.9 Business operation code matches a business operation code for the establishment

with same id in its most recent establishment registration.

4.1.4.10 If any of the products without a marketing completion date in a Prescription

Animal Drug Label (50578-4), Animal Cells, Tissues, and Cell and Tissue

Based Product Label (98075-5), OTC Animal Drug Label (50577-6) or Animal

Medicated Article or Medicated Feed Label (50576-8, 50574-3, 50573-5,

50575-0, 50572-7, 50571-9) has establishments with operations of manufacture

(C43360) and also relabel (C73607), or repack (C73606), then there is no

product source.

4.1.4.11 If the document type is Human Compounded Drug Label (75031-5), then the

establishment’s business operation is Human drug compounding outsourcing

facility (C112113).

4.1.4.12 If the document type is Animal Compounded Drug Label (77647-6), then the

establishment’s business operation is Outsourcing Animal Drug Compounding

(C122061).

4.1.4.13 If the product has a product source reference (source NDC product code), then

one of the operations is Repack (C73606) or Relabel (C73607) except if the SPL

file is for Salvaged Drugs, i.e. having business operation as salvage (C70827).

4.1.4.14 If in a Bulk Ingredient (53409-9) or Bulk ingredient – Animal Drug (81203-2)

listing there is a product with marketing category Bulk Ingredient (C73626) and

SPL Implementation Guide with Validation Procedures v1

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without a marketing completion date, then one or more establishments with

operation of API Manufacture (C82401) are included.

4.1.4.15 If there is any product that is or includes a drug or biologic and has no marketing

completion date and no product source, then at least one establishment with a

manufacture operation is included such as API Manufacture (C82401),

Manufacture (C43360), or Positron Emission Tomography Drug Production

(C91403).

4.1.4.16 If in a Prescription Animal Drug Label (50578-4), OTC Animal Drug Label

(50577-6) or Animal Medicated Article or Medicated Feed Label (50576-8,

50574-3, 50573-5, 50575-0, 50572-7, 50571-9) there is a product without a

marketing completion date, with an active ingredient other than those in the

designated medical gas validation list, and without product source, then one or

more establishments with operation of API Manufacture (C82401) are included.

4.1.4.17 If the marketing status code for any of the products that is or includes a drug is

completed and the document type and marketing categories are as follows, then

there are one or more establishments. For document type Bulk Ingredient

(53409-9) the marketing category Bulk Ingredient for Human Prescription

Compounding (C96793); for document type Human OTC Drug Label (34390-5)

the marketing categories OTC Monograph Drug Product Manufactured Under

Contract (C132334), Unapproved Drug Other (C73627), Unapproved Drug

Homeopathic (C73614), Unapproved Drug Product Manufactured Under

Contract (C132335), and OTC Monograph Drug (C200263); for document type

Human Prescription Drug Label (34391-3) the marketing categories Approved

Drug Product Manufactured Under Contract (C132333), NDA Authorized

Generic (C73605), Export Only (C73590), ANDA (C73584), BLA (C73585),

IND (C75302), NDA (C73594), Unapproved Drug for Use in Drug Shortage

(C101533), Unapproved Homeopathic (C73614), Unapproved Medical Gas

(C73613), Unapproved Drug Other (C73627), and Unapproved Drug Product

Manufactured Under Contract (C132335); and for the marketing category BLA

(C73585) the document types License Blood Intermediates/Paste Label (53407-

3), Licensed Minimally Manipulated Cells Label (53408-1), Cellular Therapy

(60684-8), Licensed Vaccine Bulk Intermediate Label (53406-5), Non-

Standardized Allergenic Label (53405-7), Plasma Derivative (60683-0),

Standardized Allergenic (60682-2), and Vaccine Label (53404-0).

Table 8: Document Types and Marekting Categories for which even completed product listings

should have establishments.

GRP

Document Type

DTCode

Marketing Category

MCCode

Name

Code

Name

Code

Bulk Ingredient 53409-9 Bulk Ingredient for Human

Prescription Compounding

C96793

Cellular Therapy

60684-8

BLA

C73585

Drug and Biologics Labeling, Listing, and other Product Submission

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Human OTC Drug Label 34390-5 OTC Monograph Drug Product

Manufactured Under Contract

C132334

Human OTC Drug Label

34390-5

Unapproved Drug Other

C73627

Human OTC Drug Label 34390-5 Unapproved Drug

Homeopathic

C73614

Human OTC Drug Label 34390-5 Unapproved Drug Product

Manufactured Under Contract

C132335

Human OTC Drug Label

34390-5

OTC Monograph Drug

C200263

Human Prescription Drug Label 34391-3 Approved Drug Product

Manufactured Under Contract

C132333

Human Prescription Drug Label

34391-3

NDA Authorized Generic

C73605

Human Prescription Drug Label

34391-3

Export Only

C73590

Human Prescription Drug Label

34391-3

ANDA

C73584

Human Prescription Drug Label

34391-3

BLA

C73585

Human Prescription Drug Label

34391-3

IND

C75302

Human Prescription Drug Label

34391-3

NDA

C73594

Human Prescription Drug Label 34391-3 Unapproved Drug for Use in

Drug Shortage

C101533

Human Prescription Drug Label

34391-3

Unapproved Homeopathic

C73614

Human Prescription Drug Label

34391-3

Unapproved Medical Gas

C73613

Human Prescription Drug Label

34391-3

Unapproved Drug Other

C73627

Human Prescription Drug Label 34391-3 Unapproved Drug Product

Manufactured Under Contract

C132335

License Blood Intermediates/Paste

Label

53407-3 BLA C73585

Licensed Minimally Manipulated Cells

Label

53408-1 BLA C73585

Licensed Vaccine Bulk Intermediate

Label

53406-5 BLA C73585

Non-Standardized Allergenic Label

53405-7

BLA

C73585

Plasma Derivative

60683-0

BLA

C73585

Standardized Allergenic

60682-2

BLA

C73585

Vaccine Label

53404-0

BLA

C73585

4.1.4.18 DUNS Number is not associated with any other set id for Compounded Drug

report.

4.1.4.19 If the marketing category is OTC Monograph Drug Product Manufactured

Under Contract (C132334), OTC Monograph Drug (C200263) and business

operations is label (C84732), manufacture (C43360), pack (C84731), relabel

(C73607), or repack (C73606), then one or more establishment ids (DUNS

Numbers) matches an establishment with same id (DUNS Number) submitted in

documents of type Establishment Registration (51725-0) in the same or previous

calendar year which is associated with one or more of the business operation

qualifiers contract manufacturing for human over-the-counter drug products

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produced under a monograph (C170729) or manufactures human over-the-

counter drug products produced under a monograph (C131708).

4.1.5 Business Operation Product

The following example shows how the business operations are specified for particular

products. It is done by replicating the business operation (actDefinition) elements,

and connecting each with one product as shown below:

<code code="C43360" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="manufacture"/>

</manufacturedMaterialKind></manufacturedProduct></product>

</actDefinition></performance>

<code code="C43360" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="manufacture"/>

Validation Procedures

4.1.5.1 If the product is regulated by CDER, then an establishment operation listed is

linked to at least one listed product or part product, except for Human

Compounded Drug Label (75031-5).

4.1.5.2 If the product is regulated by CDER, then each listed product having an active

marketing status is linked from at least one establishment operation, except for

Human Compounded Drug Label (75031-5).

4.1.5.3 If the product is regulated by CDRH, CFSAN, or CVM or if it is a Human

Compounded Drug Label (75031-5) or Animal Compounded Drug Label

(77647-6), then there is no operation-product link (NDC product code-to-

establishment-business operation data relationship).

4.1.5.4 If the product is regulated by CBER, then the operation-product link is optional.

(NDC product code-to-establishment-business-operation data relationship)

4.1.5.5 An operation product link refers to the product item code of an existing product.

Drug and Biologics Labeling, Listing, and other Product Submission

112

4.2 Body

4.2.1 Required Sections

Validation Procedures

4.2.1.1 The document body contains one or more sections

4.2.1.2 One section contains the product data elements

4.2.1.3 With the exception of inner components of kits or for products with item codes

(NDC product codes) for which the marketing status code is new or cancelled,

for each product there is a representative sample image of a carton/container

label in a major SPL section with section heading Package Label.Principal

Display Panel (51945-4), except for Positron Emission Tomography drug

products (files with only one establishment and this establishment having

business operation Positron Emission Tomography Drug Production, C91403)

and Non-Standardized Allergenic Label (53405-7), Animal Compounded Drug

Label (77647-6), and Human Compounded Drug Label (75031-5) or if the SPL

file is for Salvaged Drugs, i.e., having business operation as salvage (C70827).

4.2.1.4 If the document type is Non-Standardized Allergenic Label (53405-7), then

there is at least one carton/container label in a major SPL section with section

heading Package Label.Principal Display Panel (51945-4) in the SPL, except if

there is no marketing status other than new or cancelled.

4.2.1.5 If the document type is Human Prescription Drug Label (34391-3), Prescription

Animal Drug Label (50578-4), Animal Cells, Tissues, and Cell and Tissue Based

Product Label (98075-5), or CVM document types other than Recombinant

Deoxyribonucleic Acid Construct Label (78745-7), or Intentional Animal

Genomic Alteration Label (101437-2), then there is at least one other content of

labeling section besides SPL Listing Data Elements Section (48780-1) and

Package Label.Principal Display Panel (51945-4), except if there is no

marketing category code other than Bulk Ingredient (C73626), Drug for Further

Processing (C94795), Unapproved Medical Gas (C73613), Approved Drug

Product Manufactured under Contract (C132333), OTC Monograph Drug

Product Manufactured under Contract (C132334), Unapproved Drug Product

Manufactured under Contract (C132335), Bulk Ingredient for Human

Prescription Compounding (C96793), Bulk Ingredient for Animal Drug

Compounding (C98252) or Export Only (C73590), or there is no active

ingredient other than those in the designated medical gas validation list or there

is no marketing status other than new or cancelled.

4.2.1.6 If the approval number is in the medication guide validation list and the

marketing category is not Approved Drug Product Manufactured Under

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Contract (C132333), then there is such an SPL Medguide Section (42231-1),

except if there is no marketing status other than new or cancelled.

4.2.1.7 If the document type is Human OTC Drug Label (34390-5) and the marketing

category code is not Approved Drug Product Manufactured under Contract

(C132333), OTC Monograph Drug Product Manufactured under Contract

(C132334), Unapproved drug Product Manufactured under Contract (C132335)

Export Only (C73590) or OTC Monograph Drug (C200263) and the citation is

not sunscreens (part352), then there is an OTC - Active Ingredient Section

(55106-9), except if there is no marketing status other than new or cancelled.

4.2.1.8 If the document type is 34390-5 (Human OTC Drug Label) and the marketing

category code is not C132333 (Approved Drug Product Manufactured Under

Contract), C132334 (OTC Monograph Drug Product Manufactured Under

Contract), C132335 (Unapproved drug Product Manufactured Under Contract)

or C73590 (Export Only) and the citation is not part352 (sunscreens), then there

is an OTC – Purpose section (55105-1), except if there is no marketing status

other than new or cancelled.

4.2.1.9 If the document type is 34390-5 (Human OTC Drug Label) and the marketing

category code is not C132333 (Approved Drug Product Manufactured Under

Contract), C132334 (OTC Monograph Drug Product Manufactured Under

Contract), C132335 (Unapproved Drug Product manufactured Under Contract)

or C73590 (Export Only) and the citation is not part352 (sunscreens), then there

is an OTC – keep out of reach of children section (50565-1), except if there is no

marketing status other than new or cancelled.

4.2.1.10 If the document type is 34390-5 (Human OTC Drug Label) and the marketing

category code is not C132333 (Approved Drug Product Manufactured Under

Contract), C132334 (OTC Monograph Drug Product Manufactured Under

Contract), C132335 (Unapproved Drug Product Manufactured Under Contract)

or C73590 (Export Only) and the citation is not part352 (sunscreens), then there

is an Indications & usage section (34067-9), except if there is no marketing

status other than new or cancelled.

4.2.1.11 If the document type is 34390-5 (Human OTC Drug Label) and the marketing

category code is not C132333 (Approved Drug Product Manufactured Under

Contract), C132334 (OTC Monograph Drug Product Manufactured Under

Contract), C132335 (Unapproved Drug Product Manufactured Under Contract)

or C73590 (Export Only) and the citation is not part352 (sunscreens), then there

is a Warnings section (34071-1), except if there is no marketing status other than

new or cancelled.

4.2.1.12 If the document type is 34390-5 (Human OTC Drug Label) and the marketing

category code is not C132333 (Approved Drug Product Manufactured Under

Contract), C132334 (OTC Monograph Drug Product Manufactured Under

Contract), C132335 (Unapproved Drug Product Manufactured Under Contract)

4 Dr

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114

or C73590 (Export Only) and the citation is not part352 (sunscreens), then there

is a Dosage & administration section (34068-7), except if there is no marketing

status other than new or cancelled.

4.2.1.13 If the document type is 34390-5 (Human OTC Drug Label) and the marketing

category code is not C132333 (Approved Drug Product Manufactured Under

Contract), C132334 (OTC Monograph Drug Product Manufactured Under

Contract), C132335 (Unapproved Drug Product Manufactured Under Contract)

or C73590 (Export Only) and the citation is not part352 (sunscreens), then there

is an Inactive ingredient section (51727-6), except if there is no marketing status

other than new or cancelled.

4.2.1.14 If the marketing category is “unapproved drug for use in drug shortage”

(C101533), then Health Care Provider Letter Section (71744-7) is present,

except if there is no marketing status other than new or cancelled.

4.2.1.15 Package Label.Principal Display Panel Section(s) (51945-4) are the last

section(s) in the document.

4.2.1.16 If any of the products has the marketing status code is new or cancelled, then

there may not be a content of labeling section.

4.2.2 Reporting Period (for certain submissions)

For certain drug product submission files (currently Human Compounded Drug

Label), a reporting period is provided as follows:

<code code="48780-1"

codeSystem="2.16.840.1.113883.6.1"

displayName="SPL product data elements section"/>

</effectiveTime>

Validation Procedures

4.2.2.1 If the document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6), then the product data element section’s

effective time contains the reporting period.

4.2.2.2 If the document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6), then reporting period (effective time) has

low and high boundaries for reporting period start and end date respectively.

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4.2.2.3 If the document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6), then reporting start date has at least the

precision of day in the format YYYYMMDD

4.2.2.4 If the document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6), then reporting end date has at least the

precision of day in the format YYYYMMDD

4.2.2.5 If the document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6), then reporting start date is before reporting

end date.

4.2.2.6 If the document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6), then reporting period start date (low value)

is any day of any year between 2014 to current year.

4.2.2.7 If the document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6) and the reporting period start date (low

value) is December 1, then the end date (high value) is May 31 of the following

year.

4.2.2.8 If the document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6) and the reporting period start date (low

value) is June 1, then the end date (high value) is November 30 of the same year.

4.2.2.9 If the document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6) and the reporting period start date (low

value) is not Dec 1 or Jun 1, then the reporting period end date (high value) is 6

month from the start date.

<code code="48780-1" codeSystem="2.16.840.1.113883.6.1"

displayName="SPL product data elements section"/>

<text>

<paragraph>No Products to Report.</paragraph>

</text>

4.2.2.10 If no products are reported in the product data element section of a Human

Compounded Drug Label (75031-5) or Animal Compounded Drug Label

(77647-6), i.e., the product data elements section contains no subject element,

then the product data elements section contains section text with the single

paragraph “No Products to Report” and the only section is the product data

elements section.

4.2.2.11 If the document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6) and the text section is included in the

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116

product data elements section, then there is no subject element (for the product

data elements).

4.2.2.12 If the document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6) and no products are reported, then the

facility can not be associated with any compounded drug in this period.

4.2.2.13 If the document type is Human Compounded Drug Label (75031-5) or Animal

Compounded Drug Label (77647-6) with products reported in this period, then

the establishment can not be associated with another Human Compounded Drug

Label that states “No Products to Report” for this period.

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5 NDC/NHRIC Labeler Code Request

5.1 Header

5.1.1 Document type

<code code="51726-8"

codeSystem="2.16.840.1.113883.6.1"

displayName="NDC/NHRIC Labeler Code request"/>

Validation Procedures

5.1.1.1 Document code is NDC/NHRIC Labeler Code Request (51726-8), NDC Labeler

Code Request - Animal Drug (72871-7), NDC Labeler Code Inactivation

(69968-6), or NDC Labeler Code Inactivation – Animal Drug (81204-0).

5.1.1.2 There is no title

5.1.1.3 If a document with the same set id has been previously submitted, then it is an

NDC/NHRIC Labeler Code Request (51726-8) or NDC Labeler Code Request -

Animal Drug (72871-7), NDC Labeler Code Inactivation (69968-6), or NDC

Labeler Code Inactivation – Animal Drug (81204-0).

5.1.1.4 If the document is an NDC Labeler Code Inactivation (69968-6) or NDC

Labeler Code Inactivation – Animal Drug (81204-0), then an NDC/NHRIC

Labeler Code Request (51726-8) or NDC Labeler Code Request - Animal Drug

(72871-7) document with the same set id has been previously submitted

5.1.1.5 If the document is an NDC Labeler Code Inactivation (69968-6) or NDC

Labeler Code Inactivation – Animal Drug (81204-0), then there is no labeler

information.

5.1.1.6 If the document is an NDC Labeler Code Inactivation (69968-6), or NDC

Labeler Code Inactivation – Animal Drug (81204-0), then all NDCs with the

NDC Labeler Code linked to the NDC Labeler Code Inactivation file's set ID is

associated with a product with a marketing end date, except if the NDC Labeler

Code Inactivation file was initiated by the FDA.

5 NDC/NHRIC Labeler Code Request

118

5.1.2 Labeler information

<time/>

<name>Mann's drug Store</name>

Validation Procedures

5.1.2.1 If the document is an NDC/NHRIC Labeler Code Request (51726-8) or NDC

Labeler Code Request - Animal Drug (72871-7), then there is a labeler

organization.

5.1.2.2 There are two ids (NDC/NHRIC labeler code and DUNS Number) (except for

an initial labeler code request, which should be submitted with only one id

(DUNS Number.))

5.1.2.3 One id, the DUNS number, and name are as in Section 2.1.5.

5.1.2.4 One id has the root 2.16.840.1.113883.6.69 and an extension (except for an

initial labeler code request, which should be submitted without this id

(NDC/NHRIC labeler code.))

5.1.2.5 There is no id root besides 1.3.6.1.4.1.519.1 and 2.16.840.1.113883.6.69

5.1.2.6 If no document with the same set id has been previously submitted, then the

NDC labeler code has not been associated previously with a different setId

(regardless of version)

5.1.2.7 The set id is not associated with any other id(NDC/NHRIC labeler code) with

root 2.16.840.1.113883.6.69

5.1.2.8 The id extension(NDC/NHRIC labeler code) with the root

2.16.840.1.113883.6.69 has 4 or 5 digits

5.1.2.9 The id extension(NDC/NHRIC labeler code) with the root

2.16.840.1.113883.6.69 with 5 digits does not have a leading zero

5.1.2.10 The labeler code (id extension with the root 2.16.840.1.113883.6.69) is not

(0)0000, (0)0001, (0)1500, (0)1800 or (0)1900.

5.1.2.11 There is one contact party

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5.1.2.12 If a document with the same set id has previously been submitted, then there is a

labeler code (id with the root 2.16.840.1.113883.6.69) same as the one

previously submitted under that set id (if any).

5.1.3 Labeler Detail Information

To describe details of a labeler such as physical address, US agent, and business

operations the following structure is added

<name>Mann's drug Store</name>

<name>Mann's drug Store</name>

The format is similar to the Establishment description. The only difference is that

there is only one such “Establishment” with the same DUNS number and name as the

Labeler.

Validation Procedures

5.1.3.1 If the document is not a NDC/NHRIC Labeler Code Request (51726-8), then

there is no labeler detail information.

5.1.3.2 Labeler detail information has no registrant information and exactly one

“Establishment”

5.1.3.3 Labeler detail information has exactly one “Establishment”

5.1.3.4 There is one id.

5.1.3.5 Id (DUNS Number) has the root 1.3.6.1.4.1.519.1

5.1.3.6 Id (DUNS Number) is the same as the id of the labeler organization.

5.1.3.7 Name is the same as the name of the labeler organization.

5.1.3.8 Labeler detail information has an address as in Section 2.1.6.

5 NDC/NHRIC Labeler Code Request

120

5.1.3.9 There are no further elements besides the id, name, addr, and Labeler US Agent

on this level.

5.1.3.10 The DUNS number along with the labeler details’ name and address information

match the DUNS number record in the Dun and Bradstreet database.

5.1.4 Labeler US Agent

<name>Mann's drug Store</name>

<name>Simmons Reps Company</name>

</assignedOrganization>

<code code="C73330" displayName="United States agent"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

Validation Procedures

5.1.4.1 If the country for the labeler is not “USA”, then there may be one US agent

5.1.4.2 US agent is as defined in Section 6.1.3.114

5.1.5 Labeler Operation

To describe the activity of a labeler with business operations the following structure

is added.

<name>Mann's drug Store</name>

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<code code="C43360" displayName="manufacture"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

<code code="C106643" displayName="Manufactures human

prescription drug products"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

</approval>

</subjectOf>

</actDefinition>

Validation Procedures

5.1.5.1 There are one or more labeler operation details (performance act definitions).

5.1.5.2 Each performance act definition (business operation) has one code.

5.1.5.3 Code system is 2.16.840.1.113883.3.26.1.1

5.1.5.4 Display name matches the code

5.1.5.5 The code comes from the business operations list except for import (C73599)

and united states agent (C73330).

5.1.5.6 Each business operation code is mentioned only once.

5.1.5.7 There is one or more business operation qualifier except when business

operation is analysis (C25391), API manufacture (C82401) , or SIP Foreign

Seller (C175317).

5.1.5.8 Business operation qualifier has one code.

5.1.5.9 Code system is 2.16.840.1.113883.3.26.1.1

5.1.5.10 Display name matches the code

5.1.5.11 If the business operation is manufacture (C43360), then the business operation

qualifier is Manufactures human prescription drug products (C106643),

Manufactures human over-the-counter drug products not produced under an

approved drug application or under a monograph (C131710), Manufactures

human over-the-counter drug products produced under a monograph

(C131708), Manufactures human over-the-counter drug products produced

under an approved drug application (C131709), and/or Contract manufacturing

5 NDC/NHRIC Labeler Code Request

122

for human over-the-counter drug products produced under a monograph

(C170729).

5.1.5.12 If the business operation is distributes drug products under own private label

(C73608), then the business operation qualifier is distributes human prescription

drug products (C111077) and/or distributes human over-the-counter drug

products (C111078.)

5.1.5.13 If the qualifiers Intent to compound 506e (drug shortage) drugs (C112087), No

intent to compound 506e (drug shortage) drugs (C112091), Compounding from

bulk ingredients (C112092), Not compounding from bulk ingredients

(C112093), Compounding sterile products (C112094), or Not compounding

sterile products (C112095), then the operation is Human drug compounding

outsourcing facility (C112113).

5.1.5.14 If the business operation qualifier is Distributes Human Prescription Drug

Products (C111077) and/or Distributes Human Over-the-Counter Drug

Products (C111078), then the business operation is Distributes Drug Products

under Own Private Label (C73608).

5.1.6 FDA-Initiated Labeler Code Inactivation

5.1.6.1 If the document is an FDA-initiated NDC Labeler Code Inactivation (69968-6),

FDA-Initiated NDC Labeler Code Inactivation – Animal Drug (81204-0) or an

FDA-Initiated NDC Labeler Code Re-Activation, then the proper

legalAuthenticator element is included.

5.1.6.2 One id is a DUNS number with the root 1.3.6.1.4.1.519.1

5.1.6.3 The id with the root 1.3.6.1.4.1.519.1 (DUNS number) has a 9-digit extension

5.1.6.4 The proper FDA id is provided.

5.1.6.5 The proper FDA name is provided.

5.1.6.6 If the most recent document of this setId was an FDA-Initiated NDC Labeler

Code Inactivation (69968-6) or NDC Labeler Code Inactivation – Animal Drug

(81204-0), then an FDA-Initiated NDC/NHRIC Labeler Code Request (51726-8)

SPL file with <legalAuthenticator> element has been submitted before an

NDC/NHRIC Labeler Code Request (51726-8), NDC Labeler Code Request -

Animal Drug (72871-7), NDC Labeler Code Inactivation (69968-6), or NDC

Labeler Code Inactivation – Animal Drug (81204-0) can be submitted by the

labeler.

SPL Implementation Guide with Validation Procedures v1

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5.2 Body - Empty

Use an empty document body:

<text/>

5.2.1.1 The document body is empty

6 Establishment registration

124

6 Establishment registration

Establishment registrations have only header information with a single registrant

organization and one or more registered establishments. Aside from the proper

Establishment Registration document type, two other document types can be used for

establishment registration submissions, i.e., the No Change Notification, the

Establishment Deregistration and Out of Business Notification.

6.1 Header

6.1.1 Document type

<code code="51725-0"

codeSystem="2.16.840.1.113883.6.1"

displayName="Establishment registration"/>

Validation Procedures

6.1.1.1 Document type is “Establishment registration” (51725-0), “Establishment De-

Registration” (70097-1), “No change notification” (53410-7), or “Out of

Business Notification” (53411-5).

6.1.1.2 The effective time year matches the current year.

6.1.1.3 There is no title

6.1.1.4 For a No change notification (53410-7), or Establishment De-Registration

(70097-1) the set id in this document should be the same set id included in a

previously submitted Establishment Registration (51725-0), No change

notification (53410-7), or Establishment De-Registration (70097-1), with

information about your establishment(s).

6.1.1.5 If a document with the same set id as the one in this file has been previously

submitted, then the document type of the previously submitted file is

Establishment Registration (51725-0), Establishment De-Registration (70097-1),

or No change notification (53410-7).

6.1.1.6 “No change notification (53410-7)” documents are submitted during the time

frame October 1st through December 31st of each year.

6.1.1.7 If the document type is No Change Notification (53410-7), then its most recent

Establishment Registration document is not inactivated by an FDA Agency

Initiated Compliance Action.

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6.1.1.8 If the document type is No Change Notification (53410-7) and its most recent

Establishment Registration does not have any business operation qualifiers (see

Section 6.1.7), then a full Establishment Registration file must be submitted

instead, except if all the business operations are only analysis (C25391), API

manufacture (C82401), or medicated animal feed manufacture (C84635).

6.1.1.9 If the document type is No Change Notification (53410-7) and its most recent

Establishment Registration asserts the business operation qualifier Manufactures

human over-the-counter drug products (C106645), then the Establishment

Registration must be updated by submitting a full Establishment Registration

file.

6.1.1.10 If the document type is No Change Notification (53410-7) and its most recent

Establishment Registration does not have a second id with the root

2.16.840.1.113883.4.82 (FEI number) for each establishment, then the

Establishment Registration must be updated by submitting a full Establishment

Registration file with FEI numbers.

6.1.2 Registrant information

<name>Acme drug company</name>

Validation Procedures

6.1.2.1 If the document type is “No change notification” or “Establishment De-

Registration”, then there is no registrant information.

6.1.2.2 If the document type is “Establishment registration”, then there is registrant

information.

6.1.2.3 There is one id, the DUNS number and name are as in Section 2.1.5.

6.1.2.4 The id (registrant’s DUNS Number) is not associated with any other set id of

document type “Establishment registration”, except if the other set id, which

was included in a previously submitted Establishment Registration SPL file, is

referred in the related document (RPLC).

6.1.2.5 The set id is not associated with any other registrant id (DUNS Number).

6.1.2.6 There is one contact party as in section 2.1.8.

6 Establishment registration

126

6.1.2.7 Establishment registration has no labeler information (no validation rules

defined for it).

6.1.3 Establishment Information

<name>Middleton Manufacturing company</name>

<addr>

<city>Dublin</city>

<country code="IRL" codeSystem="1.0.3166.1.2.3">Ireland</country>

</addr>

Validation Procedures

6.1.3.1 If the document type is “establishment registration”, then there are one or more

establishments.

6.1.3.2 If the document type is No change notification (53410-7) or Establishment De-

Registration (70097-1), then there is no establishment information.

6.1.3.3 Establishment has one or two id elements, one id, the DUNS number, and name

are as in Section 2.1.5.

6.1.3.4 Establishment’s DUNS number is not associated with another establishment in

the same SPL file.

6.1.3.5 Establishment’s DUNS number is not associated with any other set id for

document type “Establishment registration”, except if the other set id, which

was included in a previously submitted Establishment Registration SPL file, is

referred in the relatedDocument (RPLC, see Section 2.1.11 Predecessor

Document for more details).

6.1.3.6 The DUNS number along with the establishment name and address information

match the DUNS number record in the Dun and Bradstreet database, except if

all establishments have only the business operations Medicated Animal Feed

Manufacture (C84635).

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6.1.3.7 If there is a second id, then its root is 2.16.840.1.113883.4.82 and the extension

(FEI number) is 7 or 10 digits

6.1.3.8 Each establishment has an address as in Section 2.1.6.

6.1.3.9 There is one contact party as in Section 2.1.8.

6.1.3.10 There is no assigned entity other than for US Agent or Import business.

6.1.3.11 If the document type is Establishment Registration (51725-0) and there is a

previously submitted document with the same set id as the one in this file where

this establishment had already been mentioned, then there is a second id with the

root 2.16.840.1.113883.4.82 (FEI number) for each establishment previously

identified by an id (DUNS number) with the root 1.3.6.1.4.1.519.1.

6.1.4 Establishment US agent

<addr>

<country code="IRL" codeSystem="1.0.3166.1.2.3">Ireland</country>

</addr>

<name>Simmons Reps Company</name>

</assignedOrganization>

<code code="C73330" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="United States agent"/>

Validation Procedures

6.1.4.1 If the country for the establishment is not “USA”, then there is one US agent

6.1.4.2 US agent element has code, code system and display name are as above

6.1.4.3 If the country for the establishment is “USA”, then there is no US agent

6.1.4.4 US agent has one id, (the DUNS number), and name are as in Section 2.1.5.

6 Establishment registration

128

6.1.4.5 US agent has a US telephone number and an email address.

6.1.4.6 The US agent’s DUNS number matches the DUNS number record in the Dun

and Bradstreet database and is for a USA location.

6.1.4.7 There is at most one US Agent.

6.1.5 Import business

<addr>

<country code="IRL" codeSystem="1.0.3166.1.2.3">Ireland</country>

</addr>

<name>Waytogo importers</name>

</assignedOrganization>

<code code="C73599" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="import"/>

Validation Procedures

6.1.5.1 If the country code for the establishment is not “USA”, then there may be one or

more import businesses.

6.1.5.2 Each business has code, code system and display name are as above.

6.1.5.3 If the country code for the establishment is USA, then there are no import

businesses

6.1.5.4 Importer has one id, the DUNS number and name are as in Section 2.1.5.

6.1.5.5 Importer has a US telephone number and email address.

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6.1.6 Establishment operation

</assignedOrganization>

<code code="C43360" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="manufacture"/>

Validation Procedures

6.1.6.1 There are one or more establishment operation details (performance act

definitions).

6.1.6.2 Each performance act definition has one code.

6.1.6.3 Code system is 2.16.840.1.113883.3.26.1.1

6.1.6.4 Display name matches the code

6.1.6.5 The code comes from the business operations list except for import (C73599),

united states agent (C73330), distributes drug products under own private label

(C73608), API/FDF analytical testing (C101509), clinical bioequivalence or

bioavailability study (C101511), FDF manufacture (C101510), in vitro

bioequivalence or bioanalytical testing (C101512), wholesale drug distributor

(C118411), and third-party logistics provider (C118412).

6.1.6.6 Each business operation code is mentioned only once per establishment.

6.1.6.7 There is no product reference.

6.1.6.8 If the business operation is Transfill (C125710), then the business operation

qualifier is Transfills Medical Gas (C126091).

6 Establishment registration

130

6.1.7 Business Operation Qualifier

...

<code code="Qualifier Code" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="Qualifier Display Name"/>

</approval>

</subjectOf>

Validation Procedures

6.1.7.1 There are one or more Business Operation Qualifiers, except if the business

operation is analysis (C25391), API manufacture (C82401), medicated animal

feed manufacture (C84635) , or SIP Foreign Seller (C175317).

6.1.7.2 Business operation qualifier has one code.

6.1.7.3 Code system is 2.16.840.1.113883.3.26.1.1

6.1.7.4 Code is from the Business Operation Qualifier List

6.1.7.5 Display name matches the code

Human Drug Compounding Outsourcing Facility Operation Qualifiers

6.1.7.6 If the business operation is Human drug compounding outsourcing facility

(C112113), then there are 2 or 3 operation qualifiers.

6.1.7.7 One of the qualifiers is Intent to compound 506e (drug shortage) drugs

(C112087) or No intent to compound 506e (drug shortage) drugs (C112091).

6.1.7.8 Qualifiers Intent to compound 506e (drug shortage) drugs (C112087) and No

intent to compound 506e (drug shortage) drugs (C112091), both should not be

present at a time.

6.1.7.9 One of the qualifiers is Compounding from bulk ingredients (C112092) or Not

compounding from bulk ingredients (C112093).

6.1.7.10 If one of the business operation qualifiers is compounding from bulk ingredients

(C112092), then one of the following business operation qualifiers should be

included: Compounding sterile products (C112094), and Not compounding

sterile products (C112095).

6.1.7.11 If one of the business operation qualifiers is Not compounding from bulk

ingredients (C112093), then the following business operation qualifiers should

SPL Implementation Guide with Validation Procedures v1

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not be included: Compounding sterile products (C112094), and Not

compounding sterile products (C112095).

6.1.7.12 If the qualifiers Intent to compound 506e (drug shortage) drugs (C112087), No

intent to compound 506e (drug shortage) drugs (C112091), Compounding from

bulk ingredients (C112092), Not compounding from bulk ingredients

(C112093), Compounding sterile products (C112094), or Not compounding

sterile products (C112095), then the operation is Human drug compounding

outsourcing facility (C112113).

Over-the-Counter Drug Operation Qualifiers

6.1.7.13 Instead of the business operation qualifier Manufactures human over-the-

counter drug products (C106645), either Manufactures human over-the-counter

drug products produced under an approved drug application (C131709),

Manufactures human over-the-counter drug products not produced under an

approved drug application or under a monograph (C131710), Manufactures

human over-the-counter drug products produced under a monograph

(C131708), or Contract manufacturing for human over-the-counter drug

products produced under a monograph (C170729) must be used.

6.1.7.14 If the business operation qualifier is Contract manufacturing for human over-

the-counter drug products produced under a monograph (C170729) or

manufactures human over-the-counter drug products produced under a

monograph (C131708), then the business operation is label (C84732),

manufacture (C43360), pack (C84731), relabel (C73607), or repack(C73606).

6.2 Body - Empty

Use an empty document body:

<text/>

6.2.1.1 The document body is empty

7 Out of Business Notification

132

7 Out of Business Notification

The Out of Business Notification allows de-listing of all the establishments of an

Establishment registration.

7.1 Header

7.1.1 Document type

<code code="53411-5"

codeSystem="2.16.840.1.113883.6.1"

displayName="Out of business notification"/>

Validation Procedures

7.1.1.1 Document type is “Out of business notification” (53411-5)

7.1.1.2 The effective time year matches the current year.

7.1.1.3 There is no title

7.1.1.4 An Establishment Registration (51725-0), Establishment De-Registration

(70097-1), No change notification (53410-7), Identification of CBER-regulated

generic drug facility (72090-4), Wholesale Drug Distributors and Third-Party

Logistics Facility Report (75030-7), or Withdrawal of Wholesale Drug

Distributors and Third-Party Logistics Facility Report (77573-4) with the same

set id has been previously submitted.

7.1.1.5 If a document with the same set id has been previously submitted, then it is an

Establishment Registration (51725-0), Establishment De-Registration (70097-1),

No change notification (53410-7), Identification of CBER-regulated generic

drug facility (72090-4), Wholesale Drug Distributors and Third-Party Logistics

Facility Report (75030-7), or Withdrawal of Wholesale Drug Distributors and

Third-Party Logistics Facility Report (77573-4).

7.1.1.6 There is no labeler, registrant, or establishment information.

7.2 Body - Empty

Use an empty document body:

SPL Implementation Guide with Validation Procedures v1

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<text/>

7.2.1.1 The document body is empty

8 Pharmacologic Class Indexing

134

8 Pharmacologic Class Indexing

8.1 Header

8.1.1 Document type

<code code="60685-5" codeSystem="2.16.840.1.113883.6.1"

displayName="Indexing - Pharmacologic Class"/>

Validation Procedures

8.1.1.1 Document code is as above

8.1.1.2 If a document with the same set id has been previously submitted, then it is of

the same type.

8.1.2 Author information

Pharmacologic class indexing is maintained by FDA:

<time/>

<name>Food and Drug Administration</name>

Pharmacologic classes for Mechanism of Action (MoA), Physiologic Effect (PE),

Established Pharmaceutical Class (EPC) and some estensions (EXT) and their

hierarchy are maintained by the U.S. Department of Veterans Affairs’s MED-RT

system:

<time/>

<name>Department of Veterans Affairs</name>

Chemical structure classes and their hierarchy are maintained in the National Library

of Medicine’s (NLM) Medical Subject Heading (MeSH) system:

<time/>

<name>National Library of Medicine</name>

8.1.2.1 Author information for pharmacologic class indexing is as one of the above

SPL Implementation Guide with Validation Procedures v1

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8.2 Body

<code code="48779-3" codeSystem="2.16.840.1.113883.6.1"

displayName="SPL Indexing Data Elements Section"/>

<text/>

Validation Procedures

8.2.1 Pharmacologic Class Indexing Section

8.2.1.1 If the document type is Indexing – Pharmacologic Class (60685-5), then the

document contains one SPL Indexing Data Elements Section (48779-3) as

above.

8.2.1.2 Value of effective time is same as value of effective time in document

information.

8.2.2 Pharmacologic Class Indexing

<name>tazminic acid</name>

8.2.2.1 There is one active moiety.

8.2.2.2 There is one active moiety code.

8.2.2.3 Code system is 2.16.840.1.113883.4.9

8.2.2.4 Code and code system are the same as the parent element id’s extension and root

respectively.

8.2.2.5 There is one active moiety name

8.2.2.6 Active moiety name matches code

8.2.2.7 The same active moiety is not described in a pharmacologic class indexing

document with a different set id.

8.2.2.8 There is no document with the same set id but a different active moiety.

8 Pharmacologic Class Indexing

136

8.2.2.9 There are one or more pharmacologic class components

<code code="N0000012345" codeSystem="2.16.840.1.113883.6.345"

displayName="melhoridizing tazminate [EPC]"/>

<name>melhoridizing tazminate (MTZ)</name>

8.2.2.10 Under each pharmacologic class component, there is a code

8.2.2.11 Code system is 2.16.840.1.113883.6.345 (MED-RT) or 2.16.840.1.113883.6.177

(MeSH)

8.2.2.12 If code system is MED-RT, then the code starts with a uppercase “N”, followed

by 10 digits

8.2.2.13 If code system is MeSH, then the code starts with a uppercase “M”, followed by

7 or more digits

8.2.2.14 There is one display name

8.2.2.15 If the code system is MED-RT (2.16.840.1.113883.6.345), then display name is

the formal MED-RT name with the bracket indicating the kind of concept [EPC,

MoA, PE, EXT]

8.2.2.16 If the code system is MeSH (2.16.840.1.113883.6.177), then display name is the

preferred MeSH name with a bracket “[CS]” indicating the kind of concept

being “Chemical Structure”.

8.2.2.17 If the concept is an External Pharmacologic Class [EPC], there is a name with

the preferred FDA name.

8.2.3 Pharmacologic Class Definition

<code code="N0000012345" codeSystem="2.16.840.1.113883.6.345"

displayName="melhoridizing tazminate [EPC]"/>

<name use="L">melhoridizing tazminate (MTZ)</name>

<name use="A">melhoridizing tazminate [EPC]</name>

<name use="A">tazminic melhoridizer</name>

8.2.3.1 There are one or more pharmacologic classes.

8.2.3.2 There is one code.

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8.2.3.3 The rules for the pharmacologic class code, code system and display name are as

in the respective procedures 8.2.2.12 and following.

8.2.3.4 Code and code system are the same as the parent element id’s extension and root

respectively.

8.2.3.5 There are one or more names

8.2.3.6 One name has the use attribute “L” indicating the preferred name.

8.2.3.7 If the concept is not an Established Pharmacologic Class [EPC], then the name

with the use attribute “L” is the same as the displayName.

8.2.3.8 There are zero, one or more defining super-classes

<code code="N0000012345" codeSystem="2.16.840.1.113883.6.345"

displayName="melhoridizing tazminate [EPC]"/>

8.2.3.9 Under each defining super-class there is a code

8.2.3.10 The rules for the defining super-class code, code system and displayName are as

in the respective procedures 8.2.2.12ff

8.2.3.11 There is no other name element.

9 Dietary Supplement Labeling

138

9 Dietary Supplement Labeling

Dietary supplement labeling provides a description of the product.

9.1 Header

9.1.1 Document Type

9.1.1.1 Document types for dietary supplement labeling is 58476-3 FDA product label

Dietary supplement.

9.1.1.2 If a document with the same set id has been previously submitted, then it is of

the same type.

9.1.1.3 If the document type changes from Human Prescription Drug Label (34391-3)

or Human OTC Drug Label (34390-5) to Dietary Supplement (58476-3), then

submit a new listing file with new NDC codes for the Dietary Supplement.

9.1.1.4 The set id is not associated with any top level product with a different Labeler

Prefix

9.1.2 Labeler information

<code code="58476-3" codeSystem="2.16.840.1.113883.6.1"

displayName="Dietary Supplement"/>

<name>Acme drug company</name>

Validation Procedures

9.1.2.1 There is one labeler

9.1.2.2 There is one id, the DUNS number, and name is as in Section 2.1.5.

9.1.2.3 There is no other element besides id, name and registrant.

9.1.3 Registrant information

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139

<name>Acme drug company</name>

Validation Procedures

9.1.3.1 There may be registrant information

9.1.3.2 If there is a registrant, then there is one id, (the DUNS number) and a name as in

Section 2.1.5.

9.1.3.3 There is no other element besides id, name and establishments.

9.2 Body

9.2.1 Required Sections

Validation Procedures

9.2.1.1 The document body contains three or more sections

9.2.1.2 One section contains the product data elements

9.2.1.3 There is a Package Label.Principal Display Panel Section (51945-4) with an

image of the carton/container label including the Supplement Facts.

9.2.1.4 There is one Statement of Identity Section (69718-5).

9.2.1.5 Aside from SPL Listing Data Elements Section (48780-1), Package

Label.Principal Display Panel (51945-4) and Statement of Identity Section

(69718-5), there are only the Health Claim Section (69719-3), the Warnings

Section (34071-1) for the warning statement, the Precautions Section (42232-9)

for the notice statement, the Safe Handling Warning Section (50741-8) for the

safe handling statement, and the Dosage & Administration Section (34068-7).

10 Medical Food Labeling

140

10 Medical Food Labeling

Medical Food labeling provides a description of the product.

10.1 Header

10.1.1 Document Type

10.1.1.1 Document types for Medical Food labeling is 58475-5 FDA product label

Medical Food.

10.1.1.2 If a document with the same set id has been previously submitted, then it is of

the same type.

10.1.2 Labeler information

<code code="58475-5" codeSystem="2.16.840.1.113883.6.1"

displayName="Medical Food"/>

<name>Acme drug company</name>

Validation Procedures

10.1.2.1 There is one labeler

10.1.2.2 There is one id, the DUNS number, and name is as in Section 2.1.5.

10.1.2.3 The set id is not associated with any top level product with a different Labeler

Prefix

10.1.2.4 There is no other element besides id, name and registrant.

10.1.3 Registrant information

<name>Acme drug company</name>

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Validation Procedures

10.1.3.1 There may be registrant information

10.1.3.2 If there is a registrant, then there is one id, (the DUNS number) and a name as in

Section 2.1.5.

10.1.3.3 There is no other element besides id, name and establishments.

10.1.4 Establishment information

<name>Middleton Manufacturing company</name>

</assignedOrganization>

<code code="C43360"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="manufacture"/>

Validation Procedures

10.1.4.1 If the marketing status code for any of the products is not completed, then there

are one or more establishments.

10.1.4.2 There is one id (the DUNS number) and name is as in Section 2.1.5.

10.1.4.3 id is not used for other establishments in the file

10.1.4.4 Establishment (“assignedOrganization”) has no other element besides id and

name.

10.1.4.5 The establishment id (DUNS Number) has been submitted in a document of type

“Establishment Registration” (51725-0) on or after October 1st of the previous

year, or, if earlier, that Establishment Registration has been followed by a

document of type “No Change Notification” (53410-7) between October 1st and

December 31st of the previous or the current year.

10.1.4.6 There are one or more business operations.

10.1.4.7 Act definition display name matches code

10 Medical Food Labeling

142

10.1.4.8 The code comes from the business operations list except for import (C73599),

united states agent (C73330) and distributes drug products under own private

label (C73608)

10.1.4.9 Business operation code matches a business operation code for the establishment

with same id in its most recent establishment registration

10.2 Body

10.2.1 Required Sections

Validation Procedures

10.2.1.1 The document body contains two or more sections

10.2.1.2 One section contains the product data elements

10.2.1.3 There is a Package Label.Principal Display Panel (51945-4) Section with an

image of the carton/container label.

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11 Medical Device Labeling

11.1 Header

11.1.1 Document Type

11.1.1.1 Document types are OTC Medical Device Label (69403-4) or Prescription

Medical Device Label (69404-2).

11.1.1.2 If a document with the same set id has been previously submitted, then it is of

the same type.

11.1.2 Labeler information

<code code="..." codeSystem="2.16.840.1.113883.6.1"

displayName="..."/>

<name>Acme drug company</name>

<addr>

<streetAddressLine>1625 29th street</streetAddressLine>

<city>Camden</city>

</addr>

<name>Bob Jones</name>

</contactPerson>

</contactParty>

Validation Procedures

11.1.2.1 There is one labeler

11.1.2.2 There is one DUNS number and name.

11.1.2.3 There are no other elements.

11 Medical Device Labeling

144

11.2 Body

11.2.1 Required Sections

Validation Procedures

11.2.1.1 The document body contains three or more sections

11.2.1.2 One section contains the product data elements

11.2.1.3 There is a Package Label.Principal Display Panel (51945-4) section with an

image of the carton/container label.

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12 Billing Unit Indexing

This document links the NDC for a marketed drug product with the National Council

for Prescription Drug Programs (NCPDP) standard billing unit.

12.1 Header

12.1.1 Document Type

<code code="71446-9" codeSystem="2.16.840.1.113883.6.1"

displayName="Indexing - Billing Unit" />

Validation Procedures

12.1.1.1 The code for the document type is Indexing - Billing Unit (71446-9)

12.1.1.2 If a document with the same set id has been previously submitted, then it is of

the same type

12.1.2 Author

<name>National Council for Prescription Drug Programs</name>

Validation Procedures

12.1.2.1 The author is the “National Council for Prescription Drug Programs”

12.1.2.2 The DUNS Number for the author is 021660014

12.1.2.3 There are no other author elements than id and name.

12.2 Body

12.2.1 Indexing Section

<code code="48779-3" codeSystem="2.16.840.1.113883.6.1"

displayName="SPL indexing data elements section" />

<text/>

12 Billing Unit Indexing

146

Validation Procedures

12.2.1.1 If the document type is Indexing – Billing Unit (71446-9), then the document

contains one SPL Indexing Data Elements section as above.

12.2.1.2 Value of effective time is same as value of effective time in document

information.

12.2.2 NDC

<code code="NDC Package Code"

codeSystem="2.16.840.1.113883.6.69"/>

Validation Procedures

12.2.2.1 There is an NDC package code inside an otherwise empty container element

inside an otherwise empty manufactured product element.

12.2.2.2 NDC contains three segments divided by hyphens

12.2.2.3 Code system for NDC is 2.16.840.1.113883.6.69

12.2.2.4 The NDC matches an NDC contained in a listing / labeling document previously

submitted.

12.2.2.5 The NDC is not associated with another set id with the document type Indexing

- Billing Unit

12.2.3 Billing Unit

<code code="NDC Package Code"

codeSystem="2.16.840.1.113883.6.69"/>

</containerPackagedProduct>

<code code="NCPDPBILLINGUNIT"

codeSystem="2.16.840.1.113883.1.11.19255"/>

<value xsi:type="CV"

code="Billing Unit Code"

codeSystem="2.16.840.1.113883.2.13" xsi:type="CE"/>

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Validation Procedures

12.2.3.1 There is one billing unit code value

12.2.3.2 Billing unit value is “GM”, “ML” or “EA”

12.2.3.3 Code system for billing unit is 2.16.840.1.113883.2.13

12.2.3.4 There are no other package data elements

12.2.3.5 There are no other product data elements.

13 Generic User Fee Facility Self-Identification

148

13 Generic User Fee Facility Self-Identification

Generic user fee facility self-identification has only header information with a single

registrant organization and one or more self-identified facilitys.

13.1 Header

13.1.1 Document type

<code code="72090-4" codeSystem="2.16.840.1.113883.6.1"

displayName="Identification of CBER-regulated generic drug facility"/>

Validation Procedures

13.1.1.1 Document type is “Identification of CBER-regulated generic drug facility”

(72090-4) or “Generic Drug Facility Identification Submission” (71743-9).

13.1.1.2 The effective time year matches the current year.

13.1.1.3 There is no title

13.1.1.4 If a document with the same set id has been previously submitted, then it is of

the same type.

13.1.1.5 Documents of type “Generic Drug Facility Identification Submission” (71743-9)

are not submitted via the OC submission folder or the listed errors below need

be corrected. (Contact [email protected] for any questions.)

13.1.2 Registrant information

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<name>Green Clover Fine Drugs</name>

<addr>

<streetAddressLine>1625 29th street</streetAddressLine>

<city>Dublin</city>

<country code="IRL" codeSystem="1.0.3166.1.2.3">Ireland</country>

</addr>

<name>Julie McFadden</name>

</contactPerson>

</contactParty>

Validation Procedures

13.1.2.1 There is registrant information.

13.1.2.2 There is one id, the DUNS number and name are as in Section 2.1.5.

13.1.2.3 id (document id) is not associated with any other set id of the same document

type.

13.1.2.4 set id is not associated with any other registrant id of the same document type.

13.1.2.5 There is one contact party as in 2.1.8.

13.1.2.6 GDUFA facility identification submission has no labeler information.

13.1.3 Facility Information

<name>Middleton Manufacturing company</name>

<addr>

<city>Dublin</city>

<country code="IRL" codeSystem="1.0.3166.1.2.3">Ireland</country>

</addr>

13 Generic User Fee Facility Self-Identification

150

<addr>

<streetAddressLine>1625 29th street</streetAddressLine>

<city>Dublin</city>

<country code="IRL" codeSystem="1.0.3166.1.2.3">Ireland</country>

</addr>

<name>Patrick McDonald</name>

</contactPerson>

</contactParty>

Validation Procedures

13.1.3.1 There are one or more facilities:

13.1.3.2 Facilities have two id elements, one id, the DUNS number, and name are as in

Section 2.1.5.

13.1.3.3 DUNS number is not associated with another facility in the same SPL file.

13.1.3.4 DUNS number is not associated with any other set id of the same document

type.

13.1.3.5 The DUNS number along with the facility name and address information match

the DUNS number record in the Dun and Bradstreet database

13.1.3.6 There is a second id, the FEI with root 2.16.840.1.113883.4.82 and 7 or 10 digit

extension.

13.1.3.7 Each facility has an address as in Section 2.1.6.

13.1.3.8 There is one contact party as in Section 2.1.8.

13.1.3.9 There is no further assigned entity.

13.1.4 Facility operation

</assignedOrganization>

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<code code="C43360" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="manufacture"/>

Validation Procedures

13.1.4.1 There are one or more facility operation details (performance act definitions).

13.1.4.2 Each performance act definition has one code.

13.1.4.3 Code system is 2.16.840.1.113883.3.26.1.1

13.1.4.4 Display name matches the code

13.1.4.5 The code comes from the business operations list.

13.1.4.6 The business operation code is one of the following: API Manufacture

(C82401), FDF Manufacture (C101510), Positron Emission Tomography Drug

Production (C91403), Clinical Bioequivalence or Bioavailability Study

(C101511), In Vitro Bioequivalence or Bioanalytical Testing (C101512),

API/FDF Analytical Testing (C101509), Pack (C84731), and Repack (C73606).

13.1.4.7 Each business operation code and qualifier is mentioned only once per facility.

13.1.5 Business Operation Qualifier

The information for all facilities submitted in a Generic Drug Facility Identification

Submission and Identification of CBER-regulated Generic Drug Facility indicates

that the sites are implicitly engaged in the production of generic drugs. A “non-

generic qualifier” can be used to mark these facilities as also engaged in the

production of non-generic (brand, innovator) drugs:

...

<code code="C101886" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="manufactures non-generics"/>

</approval>

</subjectOf>

Validation Procedures

13.1.5.1 There is zero or up to two business operation qualifiers.

13.1.5.2 The qualifier has one code.

13.1.5.3 Code system is 2.16.840.1.113883.3.26.1.1

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152

13.1.5.4 Display name matches the code

13.1.5.5 The code is Manufactures Non-Generics (C101886) and/or Contract

Manufacturing (C132491)

13.1.5.6 If the business operation qualifier is Contract Manufacturing (C132491), then

business operation is FDF Manufacture (C101510) or Pack (C84731).

13.2 Body - Empty

Use an empty document body:

<text/>

13.2.1.1 The document body is empty

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14 [RESERVED]

15 Indexing - Product Concept

154

15 Indexing - Product Concept

15.1 Header

15.1.1 Document type

<code code="73815-3" codeSystem="2.16.840.1.113883.6.1"

displayName="Indexing - Product Concept"/>

Validation Procedures

15.1.1.1 Document code is as above

15.1.1.2 If a document with the same set id has been previously submitted, then it is of

the same type.

15.1.2 Author information

Product concept indexing is maintained by FDA:

<time/>

<name>Food and Drug Administration</name>

15.1.2.1 Author information for Product Concept indexing is as one of the above

15.1.3 Reference Labeling

The information about a product concept is derived from Reference Labeling. The

Reference Labeling is found in the SPL document submitted by the innovator, or, if

the innovator has stopped marketing the product, by a designated generic

manufacturer. The SPL document containing the Reference Labeling is specified

using its setId as follows:

...

</relatedDocument>

</document>

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Validation Procedures

15.1.3.1 There is reference labeling specified.

15.1.3.2 Type code attribute is as above.

15.1.3.3 There is no document id

15.1.3.4 There is a set id

15.1.3.5 Set id is a GUID

15.1.3.6 Reference labeling set id is the set id of a drug listing document.

15.1.3.7 If a product concept indexing file for the same reference labeling set id has been

previously submitted, then it is a prior version of this indexing document with

the same set id.

15.1.3.8 If a document with the same set id has been previously submitted, then it is

associated with the same reference labeling set id.

15.2 Body

<code code="48779-3" codeSystem="2.16.840.1.113883.6.1"

displayName="SPL Indexing Data Elements Section"/>

<text/>

15.2.1 Product Concept Indexing Section

15.2.1.1 If the document type is 73815-3, “Indexing - Product Concept"’, then the

document contains one SPL Indexing Data Elements section as above.

15.2.1.2 There is one or more product

15.2.2 Abstract Product/Part Concept

The Abstract Product Concept is based on the level 4 Pharmaceutical Product

Identifier defined as a dose form with its active ingredients and strengths.

<code code="ba328d9b-c64c-fca9-2ee7-9882d2ac3f32"

codeSystem="2.16.840.1.113883.3.3389" />

15 Indexing - Product Concept

156

<formCode code="C42916" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="CAPSULE, EXTENDED RELEASE" />

Validation Procedures

15.2.2.1 There is a product concept code with code system 2.16.840.1.113883.3.3389.

15.2.2.2 Code has the format of 8-4-4-4-12 hexadecimal digits where letter digits are

lower case.

15.2.2.3 Code value matches the specified properties according to the Abstract Product

Concept Code Specification (See 15.2.4).

15.2.2.4 There is a form code and it comes from the Product Concept Dosage Form List

15.2.3 Ingredient

</quantity>

<name>tazminate malate</name>

<name>MORPHINE</name>

</activeMoiety>

</ingredientSubstance>

</ingredient>

Validation Procedures

15.2.3.1 If the ingredient’s basis of strength is the active moiety (class code is

“ACTIM”), then one (and only one) active moiety, the actual basis of strength,

is stated.

15.2.3.2 Active moiety has an active moiety UNII code.

15.2.3.3 If the ingredient’s basis of strength is a reference substance (class code is

“ACTIR”), then that reference substance is specified.

15.2.3.4 If the ingredient has a basis of strength other then the reference substance, then

there is no reference substance.

15.2.3.5 Abstract product concept code should not match with any other abstract or

equivalent product concept code.

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15.2.3.6 Reference substance has an ingredient UNII code.

15.2.4 Abstract Product Concept Code Specification

The product concept code is created by computing the MD5 digest over a data

structure describing the concept code unambiguously and uniquely, i.e., the same

product concept is described by this and only this descriptor, and hence, by this and

only this hash code. MD5 hash codes are 128 bit (16 byte) number which, in

hexadecimal presentation, is 32 digits long. The hexadecimal digits are formatted in

groups of 8-4-4-12 digits separated by hyphens.

The data structure which is the input of the MD5 digest is a pipe-delimited sequence

of form code (dose form) by NCI thesaurus code only, followed by the active

ingredients separated by the “pipe delimiter” (“|”) in alphabetic order of their UNII

code. Each active ingredient is represented by the active ingredient code and the

strength.

The dosage form code may be more generalized than the dosage form used in the SPL

Listing documents. For example, “powder for solution” the code is generalized to “for

solution”. Some of these more abstract dosage form codes may not be included in the

dosage form table that can be chosen for drug listing submissions. For instance,

POWDER, FOR SUSPENSION (C42975) is generalized to FOR SUSPENSION

(C42972). The mapping between the dosage forms can be found in the Product

Concept Dosage Form list on the FDA web page.

When the basis of strength is the active moiety (ingredient/@classCodde = ‘ACTIM’)

and the active moiety UNII is different from the active ingredient UNII, then the

active moiety UNII is appended to the active ingredient UNII with a separating tilde

(“~”) character. Likewise, if the basis of strength is a reference substance,

(ingredient/@classCodde = ‘ACTIR’), then the active moiety UNII is appended to

the active ingredient UNII with a separating tilde (“~”) character.

The strength expression must be normalized to account for the fact that 10 mg in 5

mL are the same as 2 mg in 1 mL, and 1 g is the same as 1000 mg and appended with

a pipe delimiter.

Example 1: Cefutoxime Axetil (Z49QDT0J8Z) powder for suspension (C42975) 125

mg of Cefutoxime (moiety, O1R9FJ93ED) in 5 mL is put together as

“C42972|Z49QDT0J8Z~O1R9FJ93ED|2.500e1 mg/mL”, for which the MD5 digest is

“7fead104-1147-b435-1545-606b40a2cd6b”.

Exmaple 2: Trimetoprim (AN164J8Y0X) 160 mg and Sulfametoxazole

(JE42381TNV) 800 mg tablet (C42998). is put together as:

“C42998|AN164J8Y0X|160e-3 g|JE42381TNV|8.000e2 mg”, for which the MD5

digest is “8663a93b-5627-7466-306d-fd794b7d268a”.

15 Indexing - Product Concept

158

The normalized strength is computed by (1) normalizing the units by scaling the

numbers, (2) dividing the normalized strength numerator by the normalized

denominator, and (3) writing out the normalized strength number and the combined

unit.

The normalized unit for both numerator and denominator, and their factor is

determined by the following 3 step algorithm: (1) if the unit is “1” the factor is 1 and

the normalized unit symbol is the empty string; or (2) find the unit in the Table 17:

Normalized Units; or (3) if the unit is entirely embraced in square brackets “[...]”, the

factor is 1 and the normalized unit is unchanged.

Table 17: Normalized Units

Unit

Kind of Quantity

Factor

Normalized Unit

mmol

amount of substance

mmol

nmol

amount of substance

-3

mmol

meq

amount of valence

meq

cm2

Area

cm2

elapsed time

86400

elapsed time

3600

min

elapsed time

katalytic activity

Mass

-6

Mass

-3

Radioactivity

37 10

MBq

mCi

Radioactivity

MBq

Volume

-3

All units which are entirely enclosed in in brackets are represented as is with the

trivial conversion factor 1.

With this the normalized strength value is computed as:

(normalized strength number) =

(strength numerator number) × (conversion factor of numerator unit)

÷ [ (strength denominator number) × (conversion factor of denominator unit) ]

In this example 125 mg in 5 mL, this is trivial because the conversion factors are 1.

(strength numberator number) = 125

(conversion factor of numerator unit mg) = 1

(strength denominator number) = 5

(conversion factor of denominator unit mL) = 1

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(normalized strength number) =

125 × 1

÷ ( 5 × 1 ) = 25.

If the strength had been written as 125 g in 5 L, the calculation would be:

(strength numerator number) = 125

(conversion factor of numerator unit g) = 1000

(strength denominator number) = 5

(conversion factor of denominator unit L) = 1000

(normalized strength number) =

125 × 1000

÷ ( 5 × 1000 ) = 25

Finally, the combined normalized strength number is written in the scientific notation

in the format “-9.000e-9”, where “-9.000” means 4 digits, always starting with a non-

zero digit before the decimal point, with an optional negative sign, and the decimal

point always in the same position, “e” (lower case) is the exponent marker, verbatim

as a lower case “e”, and “-9” is the exponent to base 10, with the optional negative

sign followed by however many digits are required, but no zero padding. Examples

25 is formatted as “2.500e1”, 0.3766667 as “3.767e-1”, and 250 × 10

“2.500e12.

The normalized formatted strength number is followed by a space and then the

normalized numerator unit, followed by a solidus (or “forward slash”, “/”) and the

normalized denominator unit. For example, “mg” in “mL” becomes “mg/mL”). If the

normalized denominator unit symbol is the empty string (i.e., the denominator unit

was “1”), no solidus is appended (e.g., “mg” and the empty string becomes “mg”, not

“mg/” nor “mg/1”). No attempt at canceling numerator and denominator units is made

(e.g., “mg/mg” stays unchanged and is not reduced to 1.)

15.2.5 Abstract Kit Concept Code Specification

The product kit concept code is created by computing the MD5 digest over a data

structure describing the concept code unambiguously and uniquely. The format of the

kit concept code is the same as that of the product concept code expalined in Section

15.2.4

If the form code is "kit" (C47916), the input of the MD5 digest is a pipe-delimited

sequence of form code (C47916) followed by the product concept code and quantity

of each part in alphabetic order of their product concept codes.

The quantity of the part must be normalized to account for the fact that 1 g is the

same as 1000 mg, etc. as explained in the previous section for the normalization of

strength and strength unit. The denominator value for part quantity will be always 1

and the normalization rules simplify to:

15 Indexing - Product Concept

160

The normalized part quantity is computed by (1) normalizing the numerator unit by

scaling the number and (2) writing out the normalized part quantity numerator

number and unit.

The normalized part quantity numerator unit and its factor is determined by the

following 3 step algorithm: (1) if the unit is “1” the factor is 1 and the normalized unit

symbol is the empty string; or (2) find the unit in the Table 17: Normalized Units; or

(3) if the unit is entirely embraced in square brackets “[...]”, the factor is 1 and the

normalized unit is unchanged.

Exmaple: a kit with 16.8 mL of part A (abstract concept code a46c150b-8203-ac62-

31ef-adb5c0aca5a2) and 0.9 g of part B (abstract concept code bdce178d-00b2-6beb-

4d96-259f444aee1d).

With this the normalized part quantity value is computed for each part as:

(normalized part quantity numerator number) =

(part quantity numerator number) × (conversion factor of numerator unit)

In this example, part 1: 16.8 mL:

(part quantity numerator number) = 16.8

(conversion factor of numerator unit mg) = 1

(normalized part quantity number) = 16.7 × 1 = 25.

(normalized part quantity unit) = mL.

Part 2: 0.9 g

(part quantity numerator number) = 0.9

(conversion factor of numerator unit mg) = 1000

(normalized part quantity number) = 0.9 × 1000 = 900.

(normalized part quantity unit) = mg.

Finally, the normalized part quantity number is written in the scientific notation in the

format “-9.000e-9”, where “-9.000” means 4 digits, always starting with a non-zero

digit before the decimal point, with an optional negative sign and the decimal point

always in the same position, “e” (lower case) is the exponent marker, verbatim as a

lower case “e”, and “-9” is the exponent to base 10, with the optional negative sign

followed by however many digits are required, but no zero padding. Examples 16.8 is

formatted as “1.680e1”, 900 as “9.000e2”, and 0.25 as “2.500e-1.

The normalized formatted part quantity number is followed by a space and then the

normalized numerator unit.

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In this example; “C47916|a46c150b-8203-ac62-31ef-adb5c0aca5a2|1.680e1 mL|

bdce178d-00b2-6beb-4d96-259f444aee1d|9.000e2 mg”, for which the MD5 digest is

“a76b62f9-257b-7918-620e-4db706c928f8”.

15.2.6 Application Product/Kit Concept

The Application Product Concept includes the marketing application identifier in

addition to the dose form with its active ingredients and strengths.

<code code="d5ecf7af-bb51-2003-61fe-b81973321293"

codeSystem="2.16.840.1.113883.3.3389"/>

<code code="41b5afb1-84d4-83c3-f095-5557b06994a0"

codeSystem="2.16.840.1.113883.3.3389"/>

</definingMaterialKind>

</asEquivalentEntity>

Validation Procedures

15.2.6.1 There is an product/kit concept code with code system

2.16.840.1.113883.3.3389

15.2.6.2 Code has the format of 8-4-4-4-12 hexadecimal digits where letter digits are

lower case.

15.2.6.3 Code value matches the specified properties according to the Application

Product Concept Code Specification (See 15.2.8).

15.2.6.4 There is no form code.

15.2.6.5 There is an equivalent product reference.

15.2.6.6 There is an equivalence code with code system 2.16.840.1.113883.3.2964.

15.2.6.7 Equivalence code is “A”, “B”, “OTC”, or “N”.

15.2.6.8 Equivalent product/kit concept code should not match with any other abstract or

equivalent product/kit concept code.

15.2.6.9 There is a product/kit concept reference with code and code system same as

another product/kit concept code of an Abstract or Application Product Concept

in the same document.

15 Indexing - Product Concept

162

15.2.7 Marketing Category and Application Number

</manufacturedProduct>

<code code="C73594" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="NDA" />

</territory>

</territorialAuthority>

</author>

</approval>

</subjectOf>

</manufacturedProduct>

</subject>

Validation Procedures

15.2.7.1 There is one marketing category for every Product Equivalence

15.2.7.2 The marketing authorization should only be ANDA, BLA or NDA

15.2.8 Application Product/Kit Concept Code Specification

The Application Product Concept code is created by computing the MD5 digest over

a data structure describing the Application Product concept code unambiguously and

uniquely, i.e., the same equivalent product concept is described by this and only this

descriptor, and hence, by this and only this hash code. MD5 hash codes are 128 bit

(16 byte) number which, in hexadecimal presentation, is 32 digits long. The

hexadecimal digits are formatted in in groups of 8-4-4-12 digits separated by

hyphens.

The data structure which is the input of the MD5 digest is a pipe-delimited sequence

of abstract product concept code and the application number separated by the “pipe

delimiter” (“|”).

Example 1: Cefutoxime Axetil (Z49QDT0J8Z) powder for suspension (C42975) 125

mg of Cefutoxime (moiety, O1R9FJ93ED) in 5 mL is put together as

“C42972|Z49QDT0J8Z~O1R9FJ93ED|2.500e1 mg/mL”, for which the MD5 digest is

“7fead104-1147-b435-1545-606b40a2cd6b”. That is the abstract product concept.

Example 1a: a powder for suspension for 125 mg in 5 mL has the application number

NDA050672, so its Application Product Concept is the MD5 hash of “7fead104-

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1147-b435-1545-606b40a2cd6b|NDA050672” which is “3b35d65f-9dc2-104c-e6be-

8df3d2dfb11d”.

Example 1b: Cefutoxime Axetil by Choice Pharma LLC for suspension for 125 mg in

5 mL may have the application number ANDA987654, so its Application Product

Concept is the MD5 hash of “7fead104-1147-b435-1545-

606b40a2cd6b|ANDA987654” which is “08007c2a-e9e4-0427-ea61-4d8197b2ef24”.

Exmaple 2: For abstrct product kit concept, MD5 digest is the sequence of form code

(kit, C47916) followed by the abstract product concept code and normalized part

quantity in alphabetic order of the abstract product concept code put together as

"C47916|a46c150b-8203-ac62-31ef-adb5c0aca5a2|1.680e1 mL|bdce178d-00b2-6beb-

4d96-259f444aee1d|9.000e2 mg", for which the MD5 digest is “a76b62f9-257b-

7918-620e-4db706c928f8”. This is the abstract product kit concept code.

Example 2a: For application number BLA456789, Applicaiton Product Kit Concept

is the MD5 hash of “a76b62f9-257b-7918-620e-4db706c928f8|BLA456789” which is

“a071563f-e74e-a06c-33c2-2c4aeec1b950”.

Note: the concept hash code for an Application Product Concept is always formed

from the Abstract Product Concept and the application number despite the fact that

the ANDA equivalent product references the referenced product as its equivalent. The

Application Product Concept however is Independent of the choice of equivalence

product only dependent on the Abstract Product Concept and the application number.

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16 Lot Distribution Report

16.1 SPL Header

16.1.1 Document type

<code code="66105-8" codeSystem="2.16.840.1.113883.6.1"

displayName="Lot Distribution Data"/>

Validation Procedures

16.1.1.1 Document code is as above

16.1.1.2 If a document with the same set id has been previously submitted, then it is of

the same type.

16.1.2 Author information

<id extension="Manufacturer License Number"

root="1.3.6.1.4.1.32366.1.3.1.2"/>

<name>Zwerg Pharma, Inc.</name>

<name>Bob Jones</name>

</contactPerson>

</contactParty>

16.1.2.1 There is one author (labeler)

16.1.2.2 There are two ids

16.1.2.3 One id is the DUNS number with the root 1.3.6.1.4.1.519.1 with a 9-digit

extension

16.1.2.4 One id is the manufacturer license number with the root

1.3.6.1.4.1.32366.1.3.1.2 with a 4-digit extension

16.1.2.5 There may be one contact party (see the Procedures for contact party above)

16.1.2.6 Contact party has an email address specified.

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16.1.3 Bulk-Lot Manufacturers

The manufacturing establishments which will be referred to in the bulk lot suppliers

are listed here.

<name>Middleton Manufacturing company</name>

</assignedOrganization>

</assignedEntity>

...

Validation Procedures

16.1.3.1 There are one or more bulk lot manufacturers.

16.1.3.2 There is no registrant information.

16.1.3.3 Bulk-lot manufacturer has one id (the DUNS number) and a name as in Section

2.1.5.

16.1.3.4 Each bulk-lot manufacturer appears only once.

16.1.3.5 Bulk-lot manufacturer (“assignedOrganization”) has no other element besides id

(the DUNS Number) and name.

16.1.3.6 The bulk-lot manufacturer id (DUNS Number) has been submitted in a

document of type “Establishment Registration” (51725-0) on or after October

1st of the previous year, or, if earlier, that Establishment Registration has been

followed by a document of type “No Change Notification” (53410-7) between

October 1st and December 31st of the previous or the current year.

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16.2 Body

<code code="48780-1"

codeSystem="2.16.840.1.113883.6.1"

displayName="SPL product data elements section"/>

</effectiveTime>

Validation Procedures

16.2.1.1 There is a document body

16.2.2 Data Elements Section

16.2.2.1 There is an SPL Data Elements section

16.2.2.2 Effective time has low and high boundaries indicating the reporting period of the

lot distribution data (reporting start date, reporting end date).

16.2.2.3 Reporting start date has at least the precision of day in the format

YYYYMMDD

16.2.2.4 Reporting end date has at least the precision of day in the format YYYYMMDD

16.2.2.5 Reporting start date is before reporting end date.

16.2.2.6 Reporting end date is the same as value of effective time in document

information.

16.2.2.7 Period of time represented by the reporting start and end date should not exceed

365 days.

16.2.2.8 Period of time represented by the reporting start and end date should not be less

than 14 days.

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16.2.3 Product Data – Single Licensed Product

<name>Multivax</name>

<formCode code="C42973" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="POWDER, FOR SOLUTION"/>

<name>HUMAN VIRUS ANTIGEN</name>

</ingredientSubstance>

</ingredient>

</instanceOfKind>

</manufacturedProduct>

<code code="C73585" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="BLA"/>

</approval>

</subjectOf>

</manufacturedProduct>

</subject>

</section>

16.2.3.1 There is one or more subject manufactured products:

16.2.3.2 There is an NDC product code

16.2.3.3 The general rules about the product item code apply as per 3.1.1.1ff.

16.2.3.4 There is a trade name

16.2.3.5 Name contains no special symbols (e.g., no “®” or “™” etc) and no “USP” or

dosage forms.

16.2.3.6 Name matches the NDC code submitted in drug listings.

16.2.3.7 NDC product item code has been previously submitted in an SPL listing file.

16.2.3.8 There are no other product data elements, such as generic name, product source,

inactive ingredients, etc.

16.2.3.9 The same product is not described in a lot distribution report with a different set

id.

16.2.3.10 There is no lot distribution report with the same set id but a different product.

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16.2.4 Dosing Specification

The dosing specification is used to compute the number of doses in any lot, or

container, such as to comply with the number of doses in fill lot/label lot requirement

specified by the regulation.

<routeCode code="C38288" displayName="oral"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

</substanceAdministration1>

</consumedIn>

Validation Procedures

16.2.4.1 There is a dosing specification element.

16.2.4.2 There is a route code, and the rules for route of administration code apply

(3.2.20.2f).

16.2.4.3 There is a dose quantity specification with a single value and unit, except for

variable dose, which do not have the dose quantity element.

16.2.4.4 Value is a number

16.2.4.5 Unit comes from the UCUM units of measures list

16.2.4.6 Value may be the number “0”.

16.2.4.7 Value should not include spaces.

16.2.5 Fill Lot

The fill lot is the lot of product which conforms to the specification of the product

regardless of packaging, i.e., it has the form and the strength specified by the listing

data for the package-Independent NDC of the product. As such the fill lot is an

instance of the product regardless of packaging.

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Validation Procedures

16.2.5.1 There is a fill lot element

16.2.5.2 The lot has an id with the following general rules for lot numbers:

16.2.5.3 There is an id extension with the reported alphanumeric lot number string

16.2.5.4 Lot number string can contain digits, upper case letters and the characters “-”

and “/”.

16.2.5.5 There is a globally unique root OID

16.2.5.6 If the product item code is an NDC, then the globally unique root OID is formed

by using the fixed prefix "1.3.6.1.4.1.32366.1.2.10." followed by the NDC

product item code represented as a number without dashes and with initial

zeroes from the labeler code segment removed (e.g., "0001-0123" becomes

10123).

16.2.5.7 If the product item code is an ISBT 128 code, then the globally unique root OID

is formed by using the fixed prefix “1.3.6.1.4.1.32366.1.2.13.” followed by a

decimal number value for the ISBT 128 facility identification number followed

by a period “.” and a decimal number value for the ISBT 128 product code, both

interpreted as a base 36 number with the digits 0-9 and A-Z, with the letter digits

having the value of 9 added to the ordinal letter position (A: 1 + 9 = 10, B = 2 +

9 = 11, ..., Z = 26 + 9 = 35); e.g., ISBT 128 product item code “W0123-E0404”

with facility identification number “W0123” interpreted in base 36: W = 23 + 9

= 32 × 36 + 0) × 36) + 1) × 36 + 2) × 36 + 3 = 53749083, and ISBT 128 product

code “E0404” interpreted in base 36: E = 5 + 9 = 14 × 36 + 0) × 36 + 4 ) × 36

+ 0) × 36 + 4 = 23519812, resulting in

“1.3.6.1.4.1.32366.1.2.13.53749083.23519812”.

16.2.6 Bulk Lot(s)

Bulk lot is the instance of raw material that goes into one or more fill lots at possibly

different strengths. As such the bulk lot represents one or more ingredient instances.

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<name>Mucinella Bobadis Antigen</name>

</kindOfMaterialKind>

</asInstanceOfKind>

</ingredientProductInstance>

<code code="C43360" displayName="manufacture"

codeSystem="2.16.840.1.113883.3.26.1.1”/>

Validation Procedures

16.2.6.1 There is one or more bulk lot elements

16.2.6.2 The lot has an id, and the general rules for lot numbers apply.

16.2.6.3 If the product item code is an NDC, then the globally unique root OID is formed

by using the fixed prefix "1.3.6.1.4.1.32366.1.2.10." followed by the NDC

Labeler Code represented as a number without initial zeroes (e.g., "0001"

becomes 1).

16.2.6.4 If the product item code is an ISBT 128 code, then the globally unique root OID

is formed by using the fixed prefix “1.3.6.1.4.1.32366.1.2.13.” followed by a

decimal number value for the ISBT 128 facility identification number

interpreted as a base 36 number with the digits 0-9 and A-Z, with the letter digits

having the value of 9 added to the ordinal letter position (A: 1 + 9 = 10, B = 2 +

9 = 11, ..., Z = 26 + 9 = 35); e.g., ISBT 128 facility identification number

“W0123” interpreted in base 36: W = 23 + 9 = 32 × 36 + 0) × 36) + 1) × 36 + 2)

× 36 + 3 = 53749083, resulting in “1.3.6.1.4.1.32366.1.2.13.53749083”.

16.2.6.5 The bulk lot references an active ingredient

16.2.6.6 Code system is 2.16.840.1.113883.4.9

16.2.6.7 There is one ingredient name

16.2.6.8 Ingredient name matches the code

16.2.6.9 The ingredient is actually listed as an ingredient of the product

16.2.6.10 The bulk lot references one manufacturer (C43360).

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16.2.6.11 There is one id

16.2.6.12 id is the DUNS number of the bulk lot manufacturing establishment with the

root 1.3.6.1.4.1.519.1 and a 9-digit extension

16.2.6.13 Bulk-lot manufacturer (“representedOrganization”) has no other element

besides id.

16.2.6.14 The bulk-lot manufacturer id is one of those listed in the bulk-lot

manufacturers in the header.

16.2.6.15 The establishment id matches an establishment with same id submitted in

documents of type “establishment registration” in the same or previous calendar

year with business operation manufacture (C43360) or API manufacture

(C82401).

16.2.6.16 The bulk lot references no other product activity

16.2.7 Label Lot(s) (Final Container Lot)

The label lot, or final container lot is the instance of the product, a portion of the fill

lot that is portioned out into individual containers.

</expirationTime>

Validation Procedures

16.2.7.1 There is one or more label lot elements

16.2.7.2 The lot has an id, and the general rules for lot numbers apply.

16.2.7.3 If the product item code is an NDC, then the globally unique root OID is formed

by using the fixed prefix "1.3.6.1.4.1.32366.1.2.10." followed by the full 10-

digit NDC code represented as a number without dashes and with initial zeroes

from the labeler code segment removed (e.g., "0001-0123-04" becomes

1012304).

16.2.7.4 If the product item code is an ISBT 128 code, then the globally unique root OID

is formed by using the fixed prefix “1.3.6.1.4.1.32366.1.2.13.” followed by a

decimal number value for the ISBT 128 facility identification number followed

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172

by a period “.” and a decimal number value for the ISBT 128 product code, both

interpreted as a base 36 number with the digits 0-9 and A-Z, with the letter digits

having the value of 9 added to the ordinal letter position (A: 1 + 9 = 10, B = 2 +

9 = 11, ..., Z = 26 + 9 = 35), and ending with a period “.” and the 3

segment of

the ISBT 128 package item code without leading zeroes; e.g., ISBT 128 product

item code “W0123-E0404-03” with facility identification number “W0123”

interpreted in base 36: W = 23 + 9 = 32 × 36 + 0) × 36) + 1) × 36 + 2) × 36 + 3

= 53749083, and ISBT 128 product code “E0404” interpreted in base 36: E = 5

+ 9 = 14 × 36 + 0) × 36 + 4 ) × 36 + 0) × 36 + 4 = 23519812, and 3

segment

“03” without zeroes, resulting in

“1.3.6.1.4.1.32366.1.2.13.53749083.23519812.3”.

16.2.7.5 There is an expiration time with a high boundary.

16.2.7.6 Expiration time has at least the precision of month in the format YYYYMM

16.2.8 Container Data Elements

</quantity>

<formCode code="C43169" displayName="bottle"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

</container>

Validation Procedures

16.2.8.1 There is a container reference

16.2.8.2 There is a quantity with a numerator and denominator

16.2.8.3 Numerator has a value greater than zero and a unit

16.2.8.4 Numerator unit matches the dosing specification unit.

16.2.8.5 Denominator has value 1 and either no unit or unit “1”

16.2.8.6 The container form code and quantity is the same as the package of the product

as described in the listing for the package NDC.

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16.2.8.7 There is a container packaged product code

16.2.8.8 Container packaged product item code is an NDC or based on ISBT-128

16.2.8.9 There is a form code and display name

16.2.8.10 Code system for form code is 2.16.840.1.113883.3.26.1.1

16.2.8.11 Display name matches form code

16.2.8.12 The container form code matches the form code specified for the container in

the listing data.

16.2.9 Containers Distributed

<code code="C106325"

displayName="Distributed per reporting interval"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

</effectiveTime>

</productEvent>

</subjectOf>

Validation Procedures

16.2.9.1 There are one or more product events

16.2.9.2 There is one quantity (Final Containers Distributed)

16.2.9.3 Quantity value is the integer number of final containers distributed.

16.2.9.4 Quantity unit is “1” or there is no unit.

16.2.9.5 There is a product event code

16.2.9.6 Code system is 2.16.840.1.113883.3.26.1.1

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16.2.9.7 The code is from the LDD Distribution Codes list and display name matches the

code.

16.2.9.8 There is one distribution product event

16.2.9.9 Container distribution event has an effective time with low boundary specifying

the Initial Distribution Date.

16.2.9.10 Initial distribution date has at least the precision of day in the format

YYYYMMDD

16.2.9.11 There should be a initial distribution date.

16.2.10 Containers Returned Data

<code code="C106328"

displayName="Returned"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

</productEvent>

</subjectOf>

16.2.10.1 There is one returned product event

16.2.10.2 Returned product event has no effective time

16.2.10.3 There is no other product event

16.2.11 Product Data – Kit with Multiple Licensed Products

When the licensed product is only part of a kit, but the kit itself is not tracked as a

“package lot”, the lot data is specified under the appropriate part of the kit, and all the

validation procedures specified for fill lot, bulk lot and label lot apply as above.

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<name p:de="Trade Name">Multivax (MixKit)</name>

<part>

If in addition the kit itself is tracked as a “package lot”, then the package lot data is

specified for the entire kit as follows:

<name p:de="Trade Name">Multivax (MixKit)</name>

</partProductInstance>

</part>

</productInstance>

</instanceOfKind>

Validation Procedures

16.2.11.1 The rules for product code and name are as for simple products

16.2.11.2 There is one or more parts, referencing label lots of these parts.

16.2.11.3 There is a product event code

16.2.11.4 There is a label lot specified elsewhere in the lot distribution report.

16.2.11.5 There are one or more product events

16.2.11.6 There is one distribution product event

16.2.11.7 There may be one returned product event

16.2.11.8 There is no other product event

17 [RESERVED]

176

17 [RESERVED]

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18 Wholesale Drug Distributor/Third-Party Logistics Facility

Report

Wholesale Drug Distribution submissions have only header information with data for

one or more reported facilities.

18.1 Header

18.1.1 Document type

<code code="75030-7"

codeSystem="2.16.840.1.113883.6.1"

displayName="wholesale drug distributor/third-party logistics

facility reporter"/>

Validation Procedures

18.1.1.1 Document type is Wholesale Drug Distributors and Third-Party Logistics

Facility Report (75030-7)

18.1.1.2 The effective time year matches the current year.

18.1.1.3 There is no title.

18.1.1.4 If a document with the same set id has been previously submitted, then it is a

Wholesale Drug Distributors and Third-Party Logistics Facility Report (75030-

7).

18.1.1.5 For Withdrawal of Wholesale Drug Distributors and Third-Party Logistics

Facility Report (77573-4) the set id in this document should be the same set id

included in a previously submitted Wholesale Drug Distributors and Third-

Party Logistics Facility Report (75030-7), with information about your

establishment(s).

18.1.2 Reporter information

<name>ACME Drug Logistics, Inc.</name>

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178

Validation Procedures

18.1.2.1 If the document type is Wholesale Drug Distributors and Third-Party Logistics

Facility Report (75030-7), then there is reporter information.

18.1.2.2 There is one id (the DUNS Number) and name as in Section 2.1.5.

18.1.2.3 id (reporter’s DUNS Number) is not associated with any other set id of

document type Wholesale Drug Distributors and Third-Party Logistics Facility

Report (75030-7)

18.1.2.4 The set id is not associated with any other reporter id (DUNS Number).

18.1.2.5 There is one contact party as in Section 2.1.8.

18.1.2.6 The Reporter's DUNS number matches the DUNS number record in the Dun and

Bradstreet database.

18.1.2.7 Facility submission has no labeler information (no validation rules defined for

it.)

18.1.3 Facility Information

<addr>

<streetAddressLine>325 Good Hope Avenue</streetAddressLine>

<city>Milwaukee</city>

</addr>

<code code="C117113" displayName="doing business as"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

<name>A.C.M.E. Logistic</name>

</asNamedEntity>

The confidentiality code “B” may be used at the facility level to indicate that the

street address of this facility should be suppressed in public data releases.

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Validation Procedures

18.1.3.1 If the document type is Wholesale Drug Distributors and Third-Party Logistics

Facility Report (75030-7), then there are one or more facilities.

18.1.3.2 Facility has a name and optionally one id (the DUNS Number) as in Section

2.1.5.

18.1.3.3 DUNS number, if present, is not associated with another facility in the same

SPL file.

18.1.3.4 DUNS number, if present, is not associated with any other set id for document

type Wholesale Drug Distributors and Third-Party Logistics Facility Report

(75030-7)

18.1.3.5 DUNS number, if present, along with the facility name and address information

match the DUNS number record in the Dun and Bradstreet database

18.1.3.6 Each facility has an address as in Section 2.1.6.

18.1.3.7 There is one contact party as in Section 2.1.8.

18.1.3.8 There is no further assigned entity under the facility.

18.1.3.9 There may be zero or more “doing business as” names (DBA names).

18.1.3.10 DBA names has code C117113 and code system 2.16.840.1.113883.3.26.1.1.

18.1.3.11 DBA name has one name element.

18.1.3.12 There may be a suffix beginning with space, and the abbreviation WDD or

3PL in square brackets.

18.1.3.13 If the suffix is [WDD], then one business operation for this facility is

Wholesale Drug Distributor (C118411).

18.1.3.14 If the suffix is [3PL], then one business operation for this facility is Third-

Party Logistics Provider (C118412).

18.1.3.15 If the facility has the same “doing business as” (DBA) name regardless of

business operation, then no suffix is specified.

18.1.3.16 The facility should not have the same “doing business as” (DBA) name with

the same business operation.

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18.1.4 Facility Business Operation

</assignedOrganization>

<code code="C118411" displayName="wholesale drug distribution"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

Validation Procedures

18.1.4.1 There are one or two facility business operation details (performance act

definitions).

18.1.4.2 Act definition (business operation) code is Wholesale Drug Distributor

(C118411) or Third-Party Logistics Provider (C118412) and code system is

2.16.840.1.113883.3.26.1.1.

18.1.4.3 Act definition (business operation) display name matches corresponding

business operation code.

18.1.4.4 Each business operation code is mentioned only once per facility.

18.1.4.5 There is no product reference.

18.1.5 License

License information is specified as shown below:

<code code="C118411" displayName="wholesale drug distribution"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

<id extension="License Number"

root="State license authority OID (see text)"/>

<code code="C118777" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="licensing"/>

</effectiveTime>

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<code code="State code from ISO 3166-2, e.g. US-MD"

codeSystem="1.0.3166.2"/>

</territory>

</territorialAuthority>

</author>

Example:

<code code="C118411" displayName="wholesale drug distribution"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

<id extension="2013-WL-123456"

root="1.3.6.1.4.1.32366.4.840.805"/>

<code code="C118777"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="licensing"/>

</effectiveTime>

</territory>

</territorialAuthority>

</author>

If the issuer of the license is not a state, but it is valid in the entire federal territory

then the ISO 3166-1 country CODE “USA” is provided and the DUNS number of the

federal agency.

</territory>

<name>Agency Name</name>

</governingAgency>

</territorialAuthority>

</author>

In case of the Drug Enforcement Agency (DEA) that DUNS number is 004234790.

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182

</territory>

</governingAgency>

</territorialAuthority>

</author>

Validation Procedures

18.1.5.1 There is one or more licenses, except if the business operation is Third-Party

Logistics Provider (C118412).

18.1.5.2 License Code is from the License Type Code list.

18.1.5.3 Display name matches the code.

18.1.5.4 Code system is 2.16.840.1.113883.3.26.1.1.

18.1.5.5 If the license is issued by a state, then the territorial authority territory is

specified with the ISO 3166-2 US state codes with code system 1.0.3166.2.

18.1.5.6 License has an id with the license number.

18.1.5.7 id has an extension, the license number.

18.1.5.8 If the license is issued by a state authority, then the id has a root beginning with

“1.3.6.1.4.1.32366.4.840” followed by a period “.” and a decimal number equal

to the value of the 2-letter ISO 3166-2 U.S. state code interpreted as a base 36

number with the digits 0-9 and A-Z, with the letter digits having the value of 9

added to the ordinal letter position (A: 1 + 9 = 10, B = 2 + 9 = 11, ..., Z = 26 + 9

= 35); e.g., Arizona, having the ISO 3166-2 “US-AZ”, i.e., the 2-letter state code

“AZ” with (A =) (1 + 9) × 36 + (Z =) (26 + 9) = 10 × 36 + 35 = 395, resulting in

“1.3.6.1.4.1.32366.4.840.395”.

18.1.5.9 License has a status code with values active, suspended, aborted (meaning

“revoked”), or completed (meaning “expired”).

18.1.5.10 License has an effective time high value (expiration date).

18.1.5.11 License has no effective time low value (license issue date not reported).

18.1.5.12 The effective time high boundary has at least the precision of day in the

format YYYYMMDD

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18.1.5.13 If the status code is completed, then the current date is later than the effective

time high value.

18.1.5.14 If the current date is later than the effective time high value, then the status

code is not active.

18.1.5.15 The combination of license number, license type and business operation, and

license issuing state is not associated with any other set id of document type

Wholesale Drug Distributors and Third-Party Logistics Facility Report (75030-

7) (see also 18.1.5.16 for further details).

18.1.5.16 The license id root should be followed by a suffix “.2”, “.3”, “.4”, or “.5” as

follows: “.2” for Third-Party Logistics Provider (C118412) facility in licensing

state, “.3” for Wholesale Drug Distributor (C118411) facility in licensing state,

“.4” for Third-Party Logistics Provider (C118412) out of licensensing state, and

“.5” for Wholesale Drug Distributor (C118411) facility out of licensing state; in

the absence of this suffix such suffix will be imputed for the purpose of the

preceding procedure 18.1.5.15.

18.1.5.17 If the license id root has the suffix “.1”, then the license issuing state and the

facility address state are not the same.

18.1.5.18 If the license id root has the suffix “.2”, then the business operation is Third-

Party Logistics Provider (C118412) and the license issuing state and the facility

address state are the same.

18.1.5.19 If the license id root has the suffix “.3”, then the business operation is

Wholesale Drug Distributor (C118411) and the license issuing state and the

facility address state are the same.

18.1.5.20 If the license id root has the suffix “.4”, then the business operation is Third-

Party Logistics Provider (C118412) and the license issuing state and the facility

address state are not the same.

18.1.5.21 If the license id root has the suffix “.5”, then the business operation is

Wholesale Drug Distributor (C118411) and the license issuing state and the

facility address state are not the same.

18.1.5.22 There are no other suffixes to the license id root.

18.1.5.23 If the territory code is “USA”, then the code system is 1.0.3166.1.2.3

18.1.5.24 If the territory is “USA”, then the issuing governing agency is specified with a

DUNS number and name.

18.1.5.25 If the territory is not “USA”, then there is no governing agency specified.

18 Wholesale Drug Distributor/Third-Party Logistics Facility Report

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18.1.5.26 If the issuing governing agency is DEA, then the DUNS number is 004234790

and the name “DEA”.

18.1.5.27 If the issuing governing agency is DEA then the license id root OID is

1.3.6.1.4.1.32366.4.840.1.

18.1.5.28 A DEA license is specified only with disciplinary actions.

18.1.5.29 There is one license per state, except a second state license can occur if there

are disciplinary actions with it.

18.1.5.30 The combination of license number, license type (business operation), license

issuing state and establishment address is not mentioned more than once in the

same document.

18.1.6 Business Operation Qualifier

<code code="C118412" displayName="third-party logistics provider"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

<code code="C123274" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="warehouses human prescription drug products"/>

18.1.6.1 There may be one business operation qualifier if the business operation is third-

party logistics provider (C118412).

18.1.6.2 There is no id.

18.1.6.3 Business operation qualifier is warehouses human prescription drug products

(C123274).

18.1.6.4 Display name matches the code.

18.1.6.5 Code system is 2.16.840.1.113883.3.26.1.1.

18.1.6.6 Business operation is third-party logistics provider (C118412).

18.1.7 Approval Disciplinary Action

<code code="disciplinary action code"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName=" disciplinary action name"/>

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</text>

</document>

</subjectOf>

When action is “other” a brief text description of the nature of the action should be

included:

<code code="C118472"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="other"/>

<text xsi:type=“ST”>brief description of nature of action</text>

</text>

</document>

</subjectOf>

Validation Procedures

18.1.7.1 There is a disciplinary action code.

18.1.7.2 Code comes from the Approval action list.

18.1.7.3 Display name matches the code

18.1.7.4 Code system is 2.16.840.1.113883.3.26.1.1.

18.1.7.5 If action is “other” (C118472), then there is a text element containing a brief

description of the nature of the action:

18.1.7.6 Text must be of xsi:type “ST” (plain text string).

18.1.7.7 Disciplinary action has an effective time.

18.1.7.8 The effective time value has at least the precision of day in the format

YYYYMMDD.

18.1.7.9 Disciplinary actions are in chronological order, i.e., most recent action last.

18.1.7.10 If the last disciplinary action is a suspension (C118406), then the license

status code is suspended or completed.

18 Wholesale Drug Distributor/Third-Party Logistics Facility Report

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18.1.7.11 If the last disciplinary action is a revocation (C118407, revoked), then the

license status code is aborted.

18.1.7.12 If the last disciplinary action is (re-)activation (C118408), then the license

status code is active.

18.1.7.13 If the last disciplinary action is a resolution (C118471, resolved), then the

license status code is active or completed.

18.1.7.14 If the last disciplinary action is “other” (C118472), then the license status

code is active, completed, suspended or aborted.

18.1.7.15 There may be one or more disciplinary action document references.

18.1.7.16 Document reference has a text element with mediaType and reference.

18.1.7.17 Reference value is the file name for a valid document attachment.

18.1.7.18 Size of document attachment is less than 1 MB.

18.1.7.19 File name extension matches the media type“.pdf”.

18.1.7.20 All pdf files associated with the document must be actually referenced from

that Wholesale Drug Distributors and Third-Party Logistics Facility Report

(75030-7) document.

18.2 Body - Empty

Use an empty document body:

<text/>

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19 40 CFR 180 TOLERANCE

19.1 Header

19.1.1 Document type

code code="3565717"

codeSystem="2.16.840.1.113883.6.275.1"

displayName="40 CFR 180 Tolerance"/>

Validation Procedures

19.1.1.1 Document type is “40 CFR 180 TOLERANCE” (3565717).

19.1.1.2 Code comes from the EPA Document type list

19.1.1.3 Code system is 2.16.840.1.113883.6.275.1

19.1.1.4 Display name matches the code

19.1.1.5 If a document with the same set id has been previously submitted, then it is of

the same type.

19.1.2 Author Information

<time/>

<name>US Environmental Protection Agency</name>

Validation Procedures

19.1.2.1 There is an author.

19.1.2.2 There are no other elements than id and name.

19.1.2.3 There is one company name.

19.1.2.4 The name matches the name in the Company Number List.

19.1.3 Docket Number

The Docket Number is specified as follows:

19 40 CFR 180 TOLERANCE

188

...

</relatedDocument>

</document>

19.2 Body

19.2.1 Main Sections

The main sections of the SPL document represent the first level paragraphs, (a), (b),

(c), etc. of the section in the regulation.

<code code="3145478" codeSystem="2.16.840.1.113883.6.275.1"

displayName="(a) General"/>

<title>(a) General.</title>

<text/>

Validation Procedures

19.2.1.1 Section codes must come from list CFR_40_180_SECTION_PARAGRAPHS.

19.2.1.2 Code system is 2.16.840.1.113883.6.275.1.

19.2.1.3 Display name matches the code.

19.2.1.4 Title of the section matches the display name of the section code.

19.2.2 Sub-Section

The first level sub sections of the SPL document represent the second level sub-

paragraphs, (1), (2), (3), etc. in the regulation.

...

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Validation Procedures

19.2.2.1 There is no section code.

19.2.2.2 There is a title with an Arabic ordinal number in parentheses, e.g., “(1)”, “(2)”,

etc.

19.2.3 Tolerance Specification

</identifiedSubstance>

<code code="40-CFR-..."

codeSystem="2.16.840.1.113883.3.149"/>

<code code="..."

codeSystem="2.16.840.1.113883.4.9"/>

</identifiedSubstance>

</analyte>

</value>

<code code="..."

codeSystem="2.16.840.1.113883.6.275.1"

displayName="..."/>

</presentSubstance>

</subject>

<code code="3565718"

codeSystem="2.16.840.1.113883.6.275.1"

displayName="General Tolerance"/>

<text>text note about this tolerance</text>

</effectiveTime>

19 40 CFR 180 TOLERANCE

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Validation Procedures

19.2.3.1 There is one identified substance with UNII code or EPA SRS tracking number.

19.2.3.2 There is one substance code.

19.2.3.3 Code system is 2.16.840.1.113883.4.9 (UNII) or 2.16.840.1.113883.6.275 (EPA

SRS tracking number).

19.2.3.4 Code and code system are the same as the parent element id’s extension and root

respectively.

19.2.3.5 There is one substance name.

19.2.3.6 If the code system is UNII, then code comes from the substance name list.

19.2.3.7 Substance name matches code.

19.2.3.8 The substanceSpecification code is formed by using the fixed prefix “40-CFR-”

followed by the section number present in document title.

19.2.3.9 Code system is 2.16.840.1.113883.3.149.

19.2.3.10 There is a code (Enforcement Analytical Method).

19.2.3.11 Code comes from the Enforcement Analytical Method list.

19.2.3.12 Display name matches the code.

19.2.3.13 There is are or more analytes, the substance(s) being measured.

19.2.3.14 Each analyte refers to one substance measured.

19.2.3.15 The rules for substance code and name are as in 19.2.3.2ff

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19.2.4 Tolerance Range and Commodity

</value>

<code code="..."

codeSystem="2.16.840.1.113883.6.275.1"

displayName="..."/>

</presentSubstance>

</subject>

<code code="3565718"

codeSystem="2.16.840.1.113883.6.275.1"

displayName="General Tolerance"/>

<text>text note about this tolerance</text>

</effectiveTime>

19.2.4.1 There are one or more reference ranges (tolerances)

19.2.4.2 Reference ranges have a value

19.2.4.3 Value is of xsi type IVL_PQ

19.2.4.4 There is a high boundary with value and unit

19.2.4.5 There is no low boundary

19.2.4.6 High boundary value is a number.

19.2.4.7 High boundary unit is “[ppm]”.

19.2.4.8 There may be a commodity specified for the tolerance.

19.2.4.9 There is a tolerance commodity code.

19.2.4.10 Code system is 2.16.840.1.113883.6.275.1.

19.2.4.11 Code comes from the Tolerance Commodity list.

19.2.4.12 Display name matches code.

19 40 CFR 180 TOLERANCE

192

19.2.4.13 There is an application type (approval).

19.2.4.14 There is an application type (approval) code.

19.2.4.15 Code system is 2.16.840.1.113883.6.275.1.

19.2.4.16 Code comes from the Application Type list.

19.2.4.17 Display name matches code.

19.2.4.18 There may be an expiration or revocation date.

19.2.4.19 Expiration or revocation date has a high boundary

19.2.4.20 Expiration or revocation date value has the format YYYYMMDD

19.2.4.21 Expiration or revocation date has no low boundary

19.2.4.22 There may be a text annotation.

19.2.5 Specific Sections and Sub-Sections

19.2.5.1 There is a section (a) General.

19.2.5.2 There is a section (b) Section 18 Emergency exemptions.

19.2.5.3 There is a section (c) Tolerances with regional restrictions.

19.2.5.4 There is a section (d) Indirect or inadvertent residues

19.2.5.5 There may be a section (e) Revoked tolerances subject to the channel of trade

provisions

19.2.5.6 There may be a section (f) Import tolerances

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20 Indexing - Biologic or Drug Substance

This document communicates the FDA-preferred non-proprietary name (specified

substance name) for the drug or biologic product associated with the application

number included in this indexing SPL document.

20.1 Header

20.1.1 Document Type

<code code="77648-4" codeSystem="2.16.840.1.113883.6.1"

displayName="Indexing - Biologic or Drug Substance"/>

Validation Procedures

20.1.1.1 The code for the document type is Indexing - Biologic or Drug Substance

(77648-4).

20.1.1.2 If a document with the same set id has been previously submitted then it is of the

same type.

20.1.2 Author

The drug/biologic substance indexing is maintained by FDA:

<name>Food and Drug Administration</name>

Validation Procedures

20.1.2.1 Author information for drug/biologic substance indexing is as one of the above.

20.1.2.2 The author is Food and Drug Administration (FDA).

20.1.2.3 There are no other author elements than id and name.

20.1.3 Related Document

The information in the drug/biologic substance indexing SPL file may be

automatically linked to the SPL document submitted by the biologic or drug product’s

distributor or manufacturer using the related document element which contains the set

20 Indexing - Biologic or Drug Substance

194

ID of the biologic or drug product’s SPL document. The related document SPL is

specified using its setId as follows:

...

</relatedDocument>

Validation Procedures

20.1.3.1 There may be a specified related document.

20.1.3.2 Type code attribute is as above.

20.1.3.3 There is no document id.

20.1.3.4 There is a set id.

20.1.3.5 Set id is a GUID.

20.1.3.6 Related document’s set id is the set id of a drug listing document.

20.1.3.7 If a drug/biologic substance indexing file for the same related document’s set id

has been previously submitted, then it is a prior version of this indexing

document with the same set id.

20.1.3.8 If a document with the same set id has been previously submitted, then it is

associated with the same related document’s set id.

20.2 Body

<code code="48779-3" codeSystem="2.16.840.1.113883.6.1"

displayName="SPL indexing data elements section"/>

</effectiveTime>

</section>

</component>

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<code code="48779-3" codeSystem="2.16.840.1.113883.6.1"

displayName="SPL indexing data elements section"/>

</effectiveTime>

</section>

Validation Procedures

20.2.1.1 There is a document body.

20.2.1.2 Document body contains one or two sections of type SPL Indexing Data

Elements.

20.2.2 Index Data Element Section(s) in General

<code code="48779-3" codeSystem="2.16.840.1.113883.6.1"

displayName="SPL indexing data elements section"/>

</effectiveTime>

</section>

</component>

Validation Procedures

20.2.2.1 Effective time has a low boundary indicating the period for the use of the

specified substance name (FDA-preferred non-proprietary name) (data effective

start date).

20.2.2.2 Data Elements section start date has at least the precision of day in the format

YYYYMMDD.

20.2.2.3 Data Elements section end date has at least the precision of day in the format

YYYYMMDD.

20.2.2.4 Data Elements section start date is before data elements section end date.

20.2.2.5 Data elements section contains information for a drug or biologic product.

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196

20.2.3 New (or only) Index Data Element Section

<code code="48779-3" codeSystem="2.16.840.1.113883.6.1"

displayName="SPL indexing data elements section"/>

</effectiveTime>

</section>

Validation Procedures

20.2.3.1 Data effective start date is same as the effective time in document information.

20.2.4 Old Index Data Element Section

<code code="48779-3" codeSystem="2.16.840.1.113883.6.1"

displayName="SPL indexing data elements section"/>

</effectiveTime>

</section>

</component>

Validation Procedures

20.2.4.1 Old data elements section contains effective time high boundary (old data

effective end date).

20.2.4.2 Old data element section comes before the new data element section.

20.2.4.3 Old SPL indexing data elements section has been submitted in the previous

version of the document.

20.2.4.4 New SPL indexing data elements section data should not match exactly to the

old SPL indexing data elements section.

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20.2.4.5 The end date of old data elements section is equal to the start date of new data

elements section.

20.2.5 Biologic/Drug Product Information

...

<name>ZARXIO</name>

<code code="PVI5M0M1GW"

codeSystem="2.16.840.1.113883.4.9"/>

<name>filgrastim-SNDZ</name>

</ingredientSubstance>

</ingredient>

</manufacturedProduct>

<code code="C73585" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="BLA"/>

Validation Procedures

20.2.5.1 There is a name, i.e., proprietary name of the product as used in product labeling

(see subsection 3.2.1.17 and following).

20.2.5.2 There is one active ingredient according to subsection 3.2.11.

20.2.5.3 The strength is not specified for the active ingredient.

20.2.5.4 The active moiety is not specified for the active ingredient.

20.2.5.5 Active ingredient is actually in the product, with the same basis of strength

(classCode).

20.2.5.6 There is a marketing category and application number as per subsection 3.1.7.

20.2.6 Specified Substance

<code code=" PVI5M0M1GW-SNDZ-1" codeSystem="2.16.840.1.113883.3.6277"

displayName="filgrastim-SNDZ"/>

20 Indexing - Biologic or Drug Substance

198

Validation Procedures

20.2.6.1 There is a specified substance code with code and code system.

20.2.6.2 Code system is 2.16.840.1.113883.3.6277.

20.2.6.3 There is a specified substance code display name.

20.2.6.4 Display name matches the specified substance code.

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21 Indexing - Warning Letter Alert

This document is to be used to connect the content of an FDA warning letter to the

product SPL document of the product(s) described in the warning letter.

21.1 Header

21.1.1 Document Type

<code code="77288-9" codeSystem="2.16.840.1.113883.6.1"

displayName="Indexing - Warning Letter Alert "/>

Validation Procedures

21.1.1.1 The code for the document type is Indexing - Warning Letter Alert (77288-9).

21.1.1.2 If a document with the same set id has been previously submitted then it is of the

same type.

21.1.2 Author

The Indexing – Warning Letter Alert file is maintained by FDA:

<name>Food and Drug Administration</name>

Validation Procedures

21.1.2.1 Author information for Indexing - Warning Letter is as one of the above.

21.1.2.2 Author organization is FDA.

21.1.2.3 There are no other author elements than id and name.

21.1.3 Reference Labeling

The information in the warning letter alert indexing SPL file may be automatically linked

to the SPL document submitted by the biologic or drug product’s distributor or

manufacturer using the related document element which contains the set ID of the

biologic or drug product’s SPL document. The SPL document containing the Reference

Labeling is specified using its setId as follows:

21 Indexing - Warning Letter Alert

200

...

</relatedDocument>

Validation Procedures

21.1.3.1 There is related document specified.

21.1.3.2 Type code attribute is as above.

21.1.3.3 There is no document id.

21.1.3.4 There is a set id.

21.1.3.5 Set id is a GUID.

21.1.3.6 Related document set id is the set id of a drug listing document.

21.1.3.7 If a warning letter alert indexing file for the same related document set id has

been previously submitted, then it is a prior version of this indexing document

with the same set id.

21.1.3.8 If a document with the same set id has been previously submitted, then it is

associated with the same related document set id.

21.2 Body

<code code="48780-1" codeSystem="2.16.840.1.113883.6.1"

displayName="SPL product data elements section"/>

</manufacturedProduct>

</subject>

</section>

</component>

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21.2.1 Indexing Section

Validation Procedures:

21.2.1.1 If the document type is Indexing – Warning Letter Alert (77288-9) then the

document contains one or more SPL Indexing Data Elements section as above.

21.2.1.2 Value of effective time is same as value of effective time in document

information.

21.2.2 Warning Letter Alert Data Element

<name>proprietary name <suffix>suffix to name</suffix></name>

<formCode code="C42998" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="tablet"/>

<name>non-proprietary name</name>

</genericMedicine>

Validation Procedures:

21.2.2.1 There is a name, i.e., proprietary name of the product as used in product labeling

SPL.

21.2.2.2 There is a generic medicine name as used in product labeling SPL.

21.2.2.3 There is a form code (dosage form).

21.2.2.4 Form code (dosage form) has the code system 2.16.840.1.113883.3.26.1.1.

21.2.2.5 There are one or more strength amounts with a numerator and denominator for

the active ingredient.

21.2.2.6 There is one or more product item codes.

21.2.2.7 If the product item code is an NDC/NHRIC (i.e., if the root is

“2.16.840.1.113883.6.69”), then the following procedures apply:

21.2.2.8 Code (NDC/NHRIC product code) has two segments separated by a hyphen.

21.2.2.9 The first segment (NDC/NHRIC labeler code) is numeric.

21.2.2.10 Segments (NDC/NHRIC product codes) follow the pattern of 4-4, 5-4 or 5-3.

21 Indexing - Warning Letter Alert

202

21.2.3 Warning Letter Date Element

If the issue described in the warning letter has been resolved, there are date elements

which can automatically inform the receiving system that the matter has been closed.

21.2.3.1 Effective time has a low boundary indicating the date the alert was issued.

21.2.3.2 Effective time may have a high boundary indicating when the issue described in

the letter has been resolved.

21.2.3.3 Warning letter alert date has at least the precision of day in the format

YYYYMMDD

21.2.3.4 Warning letter alert closure date has at least the precision of day in the format

YYYYMMDD

21.2.3.5 Warning letter alert date is before reporting end date.

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22 [RESERVED]

23 Risk Evaluation and Mitigation Strategy (REMS)

204

23 Risk Evaluation and Mitigation Strategy (REMS)

23.1 REMS Document

REMS are programs designed to ensure that the benefits of certain drugs outweigh

their risks.

23.1.1 Document type

All REMS documents have the following document type code. See Section 1 and 2 of

the SPL Implementation Guide and Validation Procedures for general rules.

<code code="82351-8" codeSystem="2.16.840.1.113883.6.1"

displayName="Risk Evaluation & Mitigation Strategies"/>

<title>Risk Evaluation and Mitigation Strategy (REMS)</title>

<setId root=“Document Set Id (UUID)”

Validation Procedures

23.1.1.1 Document type is Risk Evaluation & Mitigation Strategies (82351-8)

23.1.1.2 There is an author.

23.1.1.3 If a document with the same set id has been previously submitted, then it is of

the same type.

23.1.1.4 There is a title with the Risk Evaluation and Mitigation Strategy (REMS)

Document [PROPRIETARY (established/proper name)] or

[Established/Proper/Class Name] [Shared System] REMS.

23.1.1.5 The effectiveTime should be the date of the most recent revision or modification

of the REMS.

23.1.2 REMS Author information

<name>Sponsor Name</name>

Validation Procedures

23.1.2.1 There is one (author of document)

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23.1.2.2 There is one id, the sponsor’s DUNS number, and name is as in Section 2.1.5.

23.1.2.3 There is no other element besides id (the sponsor’s DUNS Number) and name.

23.1.3 REMS Related Document

The REMS are provided for a drug or biologic product represented by the related

document(s) SPL. As such, REMS append the related document(s) with more detail

how to evaluate and manage risks regarding the product described in the related

document(s). The related document(s) SPL document is referred to by its setId as

follows:

...

</relatedDocument>

</document>

Validation Procedures

23.1.3.1 There is at least one related document specified.

23.1.3.2 Type code for the related document is as above.

23.1.3.3 There is a set id with root and no extension.

23.1.3.4 Set id root is a GUID.

23.1.3.5 Related document set id is the set id of a product document of the specified type.

23.1.3.6 If a REMS document file for the same related document set id has been

previously submitted, then it is a prior version of this REMS document with the

same set id.

23.1.3.7 If a document with the same set id has been previously submitted, then it is

associated with the same related document set id.

23.2 Body

23.2.1 REMS Sections and Subsections

See subsection 2.1.1 of the FDA’s SPL Implementation Guide with Validation

Procedures document for general section and subsection information.

23 Risk Evaluation and Mitigation Strategy (REMS)

206

Validation Procedures

23.2.1.1 REMS document may have a REMS Timetable for Submission Assessments

(82352-6) section.

23.2.1.2 REMS documents may have a REMS Administrative Information (87523-7)

section.

23.2.1.3 If there is a REMS Administrative Information (87523-7) section, then the

REMS document must have the following sections: REMS Goals (82349-2) and

REMS Requirements (87524-5.)

23.2.1.4 If there is a REMS Administrative Information (87523-7) section, then the

REMS document must not have the section REMS Summary (82347-6).

23.2.1.5 If there is a REMS Requirements (87524-5), then the REMS document must

have the subsection REMS Applicant Requirements (87526-0.)

23.2.1.6 REMS documents that have REMS Requirements (87524-5) may have the

subsection REMS Participant Requirements (87525-2.)

23.2.1.7 If there is no REMS Administrative Information (87523-7) section, then the

REMS document may have the following sections:REMS Goals (82349-2),

REMS Medication Guide (82598-4), REMS Elements to Assure Safe Use

(82345-0), REMS Communication Plan (82344-3), and REMS Implementation

System (82350-0).

23.2.1.8 If there is no REMS Administrative Information (87523-7) section, then the

REMS document must not have the section REMS Requirements (87524-5.)

23.2.1.9 REMS documents with REMS Elements to Assure Safe Use (82345-0) may also

have REMS Summary (82347-6).

23.2.1.10 If the REMS document has any attachments, then the attachments are

referenced from within the REMS Material (82346-8) section.

23.2.2 REMS Product

REMS product description contains less detail than the description of the product

found in the related document SPL.

The beginning of the product data elements is as follows

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<code code="48780-1"

codeSystem="2.16.840.1.113883.6.1"

displayName="SPL product data elements section"/>

The limited data elements for REMS products:

<name>proprietary name (except for shared system REMS)</name>

<name>non proprietary name</name>

</genericMedicine>

</asEntityWithGeneric>

</manufacturedProduct>

Validation Procedures

23.2.2.1 Code, code system and display name are as above

23.2.2.2 There is an effective time with at least the precision of day in the format

YYYYMMDD.

23.2.2.3 There are one or more products

23.2.2.4 There is no product item code.

23.2.2.5 There is a generic name.

23.2.2.6 There is a proprietary name, except in a shared system REMS document.

23.2.2.7 There are no ingredients stated.

23.2.2.8 There is no package information.

23.2.2.9 There is no route of administrations in REMS documents.

23.2.2.10 There are no other product characteristics in REMS documents.

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23.2.3 Marketing Category and Application Number

The approval structure specifies in the <code> the marketing category under which

the product is approved for marketing. Products marketed under an approved

application have an application number in the <id extension> and application tracking

system under <id root>.

<id extension="applicationnumber"

root="FDA document tracking system OID"/>

<code code="code for marketing category"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="display name"/>

<role>

<id root="1.3.6.1.4.1.519.1"

extension="Application Holder DUNS"/>

<name>Application Holder Name</name>

</playingOrganization>

</role>

</holder>

</territory>

</territorialAuthority>

</author>

Validation Procedures

23.2.3.1 There is one marketing category for every product.

23.2.3.2 There is a marketing category code.

23.2.3.3 In a REMS SPL document, the marketing category is only ANDA (C73584),

BLA (C73585), or NDA (C73594.)

23.2.3.4 Display name matches the code

23.2.3.5 Code system is 2.16.840.1.113883.3.26.1.1

23.2.3.6 Territorial authority is as above

23.2.3.7 Marketing authorization holder is specified with DUNS number and name as

above.

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23.2.4 REMS Summary

REMS with the section REMS Elements to Assure Safe Use (ETASU) typically

include a REMS Summary. REMS with the section REMS Participant Requirements

(87525-2) should not include a REMS Summary section. The REMS Summary is an

overview of what stakeholders who participate in REMS with Elements to Assure

Safe Use (ETASU), such as healthcare providers, patients, and distributors, are

required to do under the REMS’ Elements to Assure Safe Use and Implementation

System. The information in the summary is presented as a series of tables that show

what clinical or administrative activity each stakeholder must carry out at each point

in the medication use process. It is designed to be a reader-friendly summary of the

REMS program requirements as well as a tool to facilitate the coding of REMS SPL

data elements.

The REMS Summary includes all requirements in the REMS document that are

directed towards stakeholders other than the application holder, but the summary

should not include activities that REMS participants learn about or must be aware of

but do not agree to undertake. For example, when filling out a form to enroll in the

REMS, a prescriber may be asked to understand the importance of monitoring

patients regularly. Unless they also agree to perform this monitoring, it would not be

included in the summary.

The summary is intended to be rendered as a series of tables as per the following

template, including one table for each stakeholder who participates in the REMS.

[Stakeholder Name]

[Protocol]

[Requirement]

[Protocol]

[Requirement]

In the table above, each item in brackets represents a “summary item”, and should be

replaced with appropriate text as follows:

[Stakeholder] is replaced with a description of the participant to whom the REMS

requirements apply, such as “Healthcare Providers who prescribe [drug]”. In most

cases, simply identifying the role of the participant is sufficient, but in other cases the

text will need to be more specific about the setting in which the drug is used, such as,

“Healthcare Providers who prescribe the drug in outpatient settings” or “Closed-

system outpatient pharmacies that dispense.”

[Protocol] is replaced with the step of the medication use process (prescribing,

dispensing, etc.) at which the requirement must be met, such as “Before the first

prescription ” or “After discontinuation”. Requirements in the summary are

23 Risk Evaluation and Mitigation Strategy (REMS)

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organized by the timing at which they should be carried out – not when they are

agreed to or acknowledged.

[Requirement] is replaced with the clinical, administrative, or operational activities

that the participant must carry out as part of the REMS, such as “Enroll the patient by

completing and submitting the Patient Enrollment Form”.

The language used in the requirement section is generally short and succinct, and no

more than one or two sentences in length. To facilitate transmission of the text across

the healthcare system, it should be in plain text and not use formatting such as bullets

or indentations.

When the requirement mentions a material such as an enrollment form that is also

attached or referenced in theREMS materials section, it includes a hyperlink to that

material.

When a requirement applies only to a subset of patients (e.g., the requirement applies

only to females of childbearing potential or a specific age group), the text is preceded

by a description of the patient population followed by a colon, as in the following

example: “For a female of childbearing potential: Counsel the patient on

contraception” and “For patients younger than age 3: assess the patient’s response to

the treatment”.

Within a single step of the medication use process there can be more than one

requirement. When the REMS specifies a certain order in which requirements are to

be carried out, the summary lists the requirements in that order.

In certain cases multiple stakeholders may play a similar role in the medication use

process (e.g., inpatient pharmacies and outpatient pharmacies that dispense the drug)

but be subject to significantly different REMS requirements. In these cases the

summary should include a separate table and stakeholder item for each of those

stakeholders.

Validation Procedures

23.2.4.1 REMS with the section REMS Elements to Assure Safe Use (82345-0) may include

a REMS Summary (82347-6.)

23.2.4.2 REMS with REMS Participant Requirements (87525-2) should not include a REMS

Summary section (82347-6).

23.2.5 REMS Data Elements

REMS Data Elements allow standardized terminology to be applied to the items in

the REMS Summary (82347-6) and REMSParticipant Requirements (87525-2).All

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items that appear in theREMS Summary and REMS Participant Requirements have

corresponding data elements coded using the appropriate standardized term. If an

application holder includes an item in their REMS Summary or REMS Participant

Requirements to which no standardized term applies,the application holder should

contact FDA for further assistance. REMS Data Elements allow standardized

terminology to be applied to the items in the REMS Summary (82347-6) and

REMSParticipant Requirements (87525-2). All items that appear in theREMS

Summary and REMS Participant Requirements have corresponding data elements

coded using the appropriate standardized term. If an application holder includes an

item in their REMS Summary or REMS Participant Requirements to which no

standardized term applies,the application holder should contact FDA for further

assistance.

23.2.6 REMS Data Elements: Protocol

REMS requirements are presented as the substance administration of the drug being a

component of a REMS protocol described in the REMS Summary or REMS

Participant Requirements which then has the requirements as other components of

that protocol. The basic structure is as follows:

...

<code code="REMS Protocol Code"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="REMS Protocol Code Display Name"/>

Note that sequenceNumber under the <componentOf> element is fixed as value 2.

This means that the substance administration of the drug under REMS is step 2 in the

REMS summary protocol. Step 2 means that requirements can be meant to occur

before (step 1), during (step 2), or after (step 3) the substance administration.

Substance administration is potentially a series of substance administrations

depending on the type of protocol (protocol code). If the protocol guides the overall

treatment, then substance administration represents the overall treatment beginning

with the first prescription, and ending with the last dose. If the protocol guides a

course of treatment, then the substance administration represents that course of

treatment. This is coded in the protocol code.

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Validation Procedures

23.2.6.1 If there is a REMS Participant Requirements (87525-2) section or a REMS

Summary (82347-6) section then there is a <protocol> data element within that

section.

23.2.6.2 The REMS protocol is linked with a componentOf relationship with sequence

number 2.

23.2.6.3 REMS protocol has a code.

23.2.6.4 REMS protocol code comes from the REMS Protocol Type list

23.2.6.5 REMS protocol code system is 2.16.840.1.113883.3.26.1.1.

23.2.6.6 REMS protocol display name matches the code.

23.2.7 REMS Data Elements:Requirement

The requirement is specified under a protocol as follows

<code code=“REMS Requirement Code”

displayName=”REMS Requirement Code”

codeSystem="2.16.840.1.113883.3.26.1.1">

</originalText>

</code>

</effectiveTime>

<code code="C0SH01" displayName="prescriber"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

</stakeholder>

</participation>

The requirement code original text contains a reference linking to the content of the

text which describes this requirement.

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The timing of the requirement is specified using the sequence number. Because the

substance administration step is fixed at sequence number 2, if a requirement is to

occur before the start of the drug step, the requirement’s sequence number is set to 1.

To occur after the end of the drug step, the requirement’s sequence number is set to 3.

To occur after the start of and along with the drug step, the requirement’s sequence

number is set to 2 as well.

The pause quantity element allows placing of requirement at a certain distance from

the drug step. For instance,

means that the required action is to occur 2 weeks after the end of the step in the

medication use process. And the following:

means that the required action is to occur 1 hour after the start of the step in the

medication use process, this often means “during” the medication process, e.g.,

during a treatment course, measure blood pressure. However, the pause quantity can

delay this step a lot more, allowing us to say “2 months after the initiation of

treatment”.

The pause quantity always determines a delay between the previous step and this step.

In the two examples above, the required action occurred after the start or the end of

the step in the medication use process. When the required action is to occur before the

23 Risk Evaluation and Mitigation Strategy (REMS)

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step in the medication use process, the pause quantity moves to the next step, the one

with sequence number 2.

To understand this, think about a simple 3 step action list:

1. do preparatory work

2. do the step in the medication use process

3. do follow up work

In the data model serialized into XML, we simply enter at number 2, the step in the

medication use process. We then use sequence number 1 to represent preparatory

work done before that step, and sequence number 3 to represent follow-up work done

after that step.

2. do the step in the medication use process

1. do preparatory work

3. do follow up work.

However, the data model associates the pause with the step that is delayed. So for

example:

1. do preparatory work

2. one hour after previous step, do the step in the medication use

process

3. two weeks after the previous step, do follow up work

Additionally, a requirement can be said to repeat at a certain period duration. For

example, we can say measure blood pressure 20 minutes after start of treatment and

then every 10 minutes:

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Validation Procedures

23.2.7.1 There is a REMS Requirement.

23.2.7.2 REMS requirement component has a sequence number with value 1, 2, or 3.

23.2.7.3 If sequence number is 2 or 3, then there may be a pause quantity element.

23.2.7.4 If sequence number is not 2 or 3, then there is no pause quantity element.

23.2.7.5 If sequence number is 1, a pause quantity element may be under the

componentOf parent element of the protocol ancestor element.

23.2.7.6 If sequence number is not 1, then there is no pause quantity element under the

componentOf parent element of the protocol ancestor element.

23.2.7.7 REMS Requirement has a code

23.2.7.8 REMS Requirement code system is 2.16.840.1.113883.3.26.1.1

23.2.7.9 REMS Requirement code comes from the REMS Requirement list.

23.2.7.10 REMS Requirement display name matches the code.

23.2.7.11 Every text element in the REMS summary has an associated summary

requirement code.

23.2.7.12 REMS Requirement code has an original text element with reference value.

23.2.7.13 Reference value links to the content ID of the section text of the section in

which it is contained.

23.2.7.14 Reference value can not be the same as that of a different requirement data

element.

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23.2.7.15 There may be an <effectiveTime> with a <period> element to indicate

repetition.

23.2.7.16 If there is an effectiveTime, then it has only a <period> child element.

23.2.7.17 REMS Requirements have a stakeholder

23.2.7.18 Stakeholder participation type code is PPRF.

23.2.7.19 Stakeholder has a code with code system 2.16.840.1.113883.3.26.1.1.

23.2.7.20 Stakeholder code comes from the Stakeholder list.

23.2.7.21 Stakeholder display name matches the code.

23.2.7.22 REMS Requirements may have a document reference (also considered “topic”

reference).

23.2.7.23 Document reference has an id with root and no extension.

23.2.7.24 The value of the root matches an id of a document cited as a REMS Material

(see Section 23.2.9)

23.2.8 REMS Approval

The Risk Evaluation and Mitigation Strategy (REMS) has a date of initial approval by

the agency, which means, it is approved by the agency and this is represented by the

following approval structure at the very first time a REMS substanceAdministration

with protocol is mentioned in the REMS document.

...

</protocol>

</componentOf>

<code code="C128899"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="REMS Approval"/>

</effectiveTime>

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</territory>

</territorialAuthority>

</author>

</approval>

</subjectOf>

</substanceAdministration>

</subject2>

Validation Procedures

23.2.8.1 The first mention of a REMS protocol in the summary has a REMS approval

structure (i.e. a subjectOf / approval element under the subject2 /

substanceAdministration).

23.2.8.2 Only the first mention of a REMS protocol in the summary has a REMS

approval structure (i.e. only the first subject2 / substanceAdministration has a

subjectOf / approval element).

23.2.8.3 There is a code for REMS Approval (C128899).

23.2.8.4 Code system is 2.16.840.1.113883.3.26.1.1

23.2.8.5 Display name matches the code.

23.2.8.6 There is an Initial REMS Program Approval Date (effectiveTime)

23.2.8.7 REMS Program Approval Date has at least the precision of day

(YYYYMMDD.)

23.2.9 REMS Material

Materials referenced from the REMS document under the section of type "REMS

Materials". There is a subject manufactured product with no code and only

subjectOf/document elements each of which then contain one reference.

For example, the material may be an attached PDF file to the REMS submission:

23 Risk Evaluation and Mitigation Strategy (REMS)

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...

<title>REMS SPL Pilot Counseling Material

Placeholder<reference value="#T001"/>

</title>

<reference value="Drug X_2015-11-01_Counseling

Material.pdf"/>

</text>

</document>

</subjectOf>

The material may be a PDF file which is a form with instructions on where to send

the form which was filled in:

<title>REMS SPL Pilot Dispenser Enrollment and

Agreement Form Placeholder<reference value="#T003"/>

</title>

<reference value="drug-x-dispenser-encollment-

form.pdf"/>

</text>

</document>

</subjectOf>

Validation Procedures

23.2.9.1 Each reference document has an id root

23.2.9.2 Document reference has a title element with reference (title reference).

23.2.9.3 Title reference value is present in the content ID of the section text.

23.2.9.4 Document reference has a text element with mediaType and reference (text

reference).

23.2.9.5 Text reference value is the file name for a valid document attachment.

23.2.9.6 File name extension matches the media type “.pdf”.

23.2.9.7 Same file name cannot occur under a different document id and the same

document id cannot be used with different file name.

23.2.9.8 id (document id) does not match any other id across all sections, documents, or

any id other than the id of the same document previously submitted.

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23.2.10 REMS Electronic Resource Information

REMS may include references to electronic resources used to help carry out REMS

activities. This information is captured using the document element and may be

referenced within the REMS Summary using the documentReference data element

</subjectOf>

REMS resources may be referenced as web content with an absolute URL reference

with the “http://” or https://” protocol:

<title>REMS SPL Pilot Prescriber Enrollment and

Agreement Form Placeholder

</title>

<text>

<reference value="https://company.com/drug-x-

presciber-encollment.html"/>

</text>

</document>

In cases where stakeholders are required to exchange data with the applicant,

electronic data standards such as NCPDP telecommunications standards may be

referenced. These consist of a special universal resource name (URN) which is

formed with the prefix “urn:”. For example the URN

“urn:NCPDP:D.0:P1:610674:000000000000-0000-0000-000000000005”, has five

segments of text separated by colons following the prefix “urn:”. The segments are

(1) the developer of the standard (e.g., “NCPDP”)

(2) the standard version (e.g. “D.0”),

(3) the transaction (e.g. “P1”)

(4) the destination address such as a BIN number (e.g., “610674”)

(5) the id of a REMS material document which provides instructions for how

to carry out the transaction.

<title>REMS SPL Pilot – NCPDP D0 - Patient Data </title>

<text>

<reference value="urn:NCPDP:D.0:P1:610674:00000000-0000-0000-0000

-000000000005"/>

</text>

</document>

</subjectOf>

Validation Procedures

23.2.10.1 Each reference document has an id root.

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23.2.10.2 Document reference has a title elementwith reference (title reference) .

23.2.10.3 Title reference value is present in the content ID of the section text.

23.2.10.4 Document reference has a text element with reference (text reference) but no

mediaType.

23.2.10.5 Text reference value is a URI starting with a URI scheme (“http://” or “urn:”).

23.2.10.6 If the text reference value begins with “urn:”, as for example in

“urn:NCPDP:D.0:P1:610674:000000000000-0000-0000-0000-00000000”, then

it is referencing an electronic data standard specification with five segments of

text separated by colons; (1) the first segment after the prefix “urn:” being the

organization that develops the standard (e.g., “NCPDP”),(2) the second segment

being the standard version (e.g. “D.0”), (3) the third segment being the

transaction (e.g. “P1”), (4) the fourth being destination address, such as a BIN

number (e.g., “610674”), and (5) the fifth segment being the id of a REMS

material document which provides instructions for how to carry out the

transaction

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24 [RESERVED]

25 [RESERVED]

222

25 [RESERVED]

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26 [RESERVED]

27 [RESERVED]

224

27 [RESERVED]

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28 Blanket No Changes Certification of Product Listing Data

The following data elements are being collected in the Blanket No Chnanges

Certification of Product Listing Data:

28.1 Header

28.1.1 Document type

<code code="86445-4"

codeSystem="2.16.840.1.113883.6.1"

displayName="BLANKET NO CHANGES CERTIFICATION OF PRODUCT LISTING"/>

Validation Procedures

28.1.1.1 Document type is “Blanket No Changes Certification of Product Listing”

(86445-4).

28.1.1.2 The effective time year matches the current year.

28.1.1.3 There is no title

28.1.1.4 If a document with the same set id as the one in this file has been previously

submitted, then the document type is the same.

28.1.1.5 “Blanket No Changes Certification of Product Listing” documents are submitted

during the time frame October 1st through December 31st of each year.

28.1.2 Establishment Information

<name>Establishment Name</name>

Validation Procedures

28.1.2.1 There are one or more establishment(s).

28.1.2.2 The establishment id (DUNS Number) has been submitted in a document of type

Establishment Registration (51725-0) on or after October 1st of the previous

year, or, if earlier, that Establishment Registration has been followed by a

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226

document of type No Change Notification (53410-7) between October 1st and

December 31st of the previous or the current year.

28.1.2.3 Establishment has one id element, the DUNS number, and name as in Section

2.1.5.

28.1.2.4 The most recent Establishment Registration document for this establishment is

not inactivated by an FDA Agency Initiated Compliance Action.

28.1.3 NDC/ISBT Product Codes

<code code="NDC/ISBT Product Item Code"

codeSystem="2.16.840.1.113883.6.69"/>

Validation Procedures

28.1.3.1 Each establishment is linked to at least one NDC product code or ISBT code

referenced in this document

28.1.3.2 Each NDC product code or ISBT code is linked to an establishment in this

document.

28.1.3.3 There are one or more establishments.

28.1.3.4 There is no act definition code.

28.1.3.5 With the exception of the NDC product codes or ISBT codes for the inner

components of kits (co-packaged products), there are one or more NDC product

codes or ISBT codes.

28.1.3.6 Code system is 2.16.840.1.113883.6.69 (NDC) or 2.16.840.1.113883.6.18

(ISBT).

28.1.3.7 Each product item code (NDC or ISBT) mentioned in this Blanket No Changes

Certification of Product Listing (86445-4) file has been previously submitted in

a drug/biological product listing file with a marketing status of “active”.

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28.1.3.8 The current version of the previously submitted drug/biological product listing

file for this NDC or ISBT product item code conforms to current validation

procedures.

28.1.3.9 The NDC product code in a Blanket No Changes Certification of Product

Listing (86445-4) may not have been previously included in an OTC Animal

Drug Label (50577-6), OTC Type A Medicated Article Animal Drug Label

(50576-8), OTC Type B Medicated Feed Animal Drug Label (50574-3), OTC

Type C Medicated Feed Animal Drug Label (50573-5), Prescription Animal

Drug Label (50578-4), VFD Type A Medicated Article Animal Drug Label

(50575-0), VFD Type B Medicated Feed Animal Drug Label (50572-7), VFD

Type C Medicated Feed Animal Drug Label (50571-9), or Animal Cells, Tissues,

and Cell and Tissue Based Product Label (98075-5).

28.1.3.10 If the drug listing file associated with this NDC has been identified as having

a listing deficiency, then it cannot be re-certified; the deficiency must be

corrected first. Please contact [email protected] for additional details.

28.1.3.11 Each establishment DUNS Number associated with the product item code via

its listing file has been submitted in a document of type ‘Establishment

Registration’ (51725-0) on or after October 1st of the previous year, or, if

earlier, that Establishment Registration has been followed by a document of type

“No Change Notification” (53410-7) between October 1st and December 31st of

the previous or the current year.

28.1.3.12 The NDC product code in this Blanket No Changes Certification of Product

Listing (86445-4) file may not have been previously included in a document of

type Bulk Ingredient (53409-9) with the marketing category of Bulk Ingredient

for Animal Drug Compounding (C98252).

28.1.3.13 The current version of the previously submitted drug/biological product listing

file for this NDC or ISBT product item code may not be implicated in an FDA-

Initiated Compliance Action – Drug Listing Inactivation with any open

compliance actions.

28.1.3.14 The NDC or ISBT product item code has been listed as the top-level product

in a listing file on or after January 1st of the previous year, or certified in a

Blanket No Changes Certification of Product Listing (86445-4) file on or after

October 1st but on or before December 31st of the previous year.

28.1.3.15 The product listing’s labeler DUNS number has been associated with the

NDC labeler code segment of the product through the most recent labeler code

request file.

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228

28.1.4 Authorized Agent

<author> .../

<id extension="Authorized Agent's DUNS Number"

root="1.3.6.1.4.1.519.1"/>

<name>Authorized Agent Company Name</name>

<name>Name of Authorized Agent's Contact Person</name>

Validation Procedures

28.1.4.1 There is one Authorized Agent

28.1.4.2 There is one id, (the DUNS number), and name are as in Section 2.1.5.

28.1.4.3 There is a contact party’s name as in Section 2.1.8.

28.1.4.4 There is a telephone number and email address.

28.2 Body - Empty

Use an empty document body:

<text/>

28.2.1.1 The document body is empty

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29 Human and Animal Salvaged Drug Products

29.1 Header

29.1.1 Document type

The document type can be any of the human and animal or biologic drug products

listing document types. The salvaged drug product file is not distinguished by a

certain document type, but by the fact that salvage establishments and salvaged lot

numbers are mentioned inside the document.

<code code="50578-4"

displayName="PRESCRIPTION ANIMAL DRUG LABEL"

codeSystem="2.16.840.1.113883.6.1"/>

Validation Procedures

29.1.1.1 Document type is Bulk Ingredient (53409-9), Bulk Ingredient – Animal Drug

(81203-2), Cellular Therapy (60684-8), Drug for Further Processing (78744-0),

Human OTC Drug Label (34390-5), Human Prescription Drug Label (34391-3),

License Blood Intermediates/Paste Label (53407-3), Licensed Minimally

Manipulated Cells Label (53408-1), Licensed Vaccine Bulk Intermediate Label

(53406-5), Non-Standardized Allergenic Label (53405-7), OTC Animal Drug

Label (50577-6), OTC Type A Medicated Article Animal Drug Label (50576-8),

OTC Type B Medicated Feed Animal Drug Label (50574-3), OTC Type C

Medicated Feed Animal Drug Label (50573-5), Plasma Derivative (60683-0),

Prescription Animal Drug Label (50578-4), Recombinant Deoxyribonucleic

Acid Construct Label (78745-7), Intentional Animal Genomic Alteration Label

(101437-2), Standardized Allergenic (60682-2), Vaccine Label (53404-0), VFD

Type A Medicated Article Animal Drug Label (50575-0), VFD Type B

Medicated Feed Animal Drug Label (50572-7), VFD Type C Medicated Feed

Animal Drug Label (50571-9.), or Animal Cells, Tissues, and Cell and Tissue

Based Product Label (98075-5).

29.1.1.2 The effective time year matches the current year.

29.1.1.3 There is title

29.1.1.4 If a document with the same set id as the one in this file has been previously

submitted, then the document type is the same.

29 Human and Animal Salvaged Drug Products

230

29.1.2 Establishment Information

<name>Establishment Name</name>

Validation Procedures

29.1.2.1 There is one establishment.

29.1.2.2 There is no other establishment.

29.1.2.3 Establishment has one id element, the DUNS number, and name as in Section

2.1.5.

29.1.2.4 The establishment id (DUNS Number) has been submitted in a document of type

“Establishment Registration” (51725-0) on or after October 1st of the previous

year, or, if earlier, that Establishment Registration has been followed by a

document of type “No Change Notification” (53410-7) between October 1st and

December 31st of the previous or the current year.

29.1.3 Business operation

<code code="C70827"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="SALVAGE"/>

</actDefinition>

Validation Procedures

29.1.3.1 There are one or more establishment operation details (performance act

definitions).

29.1.3.2 There is one business operation, salvage (C70827).

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29.1.3.3 If have one salvage operation, then all operations are salvage.

29.1.3.4 There is act definition code.

29.1.3.5 Code system is 2.16.840.1.113883.3.26.1.1

29.1.3.6 Display name matches the code

29.2 Body

29.2.1.1 If the document type is Bulk Ingredient (53409-9), Bulk Ingredient – Animal Drug

(81203-2),

Cellular Therapy (60684-8), Drug for Further Processing (78744-0),

Human OTC Drug Label (34390-5), Human Prescription Drug Label (34391-3),

License Blood Intermediates/Paste Label (53407-3), Licensed Minimally

Manipulated Cells Label (53408-1), Licensed Vaccine Bulk Intermediate Label

(53406-5),

Non-Standardized Allergenic Label (53405-7), OTC Animal Drug

Label (50577-6), OTC Type A Medicated Article Animal Drug Label (50576-8),

OTC Type B Medicated Feed Animal Drug Label (50574-3), OTC Type C

Medicated Feed Animal Drug Label (50573-5), Plasma Derivative (60683-0),

Prescription Animal Drug Label (50578-4), Recombinant Deoxyribonucleic Acid

Construct Label (78745-7), Intentional Animal Genomic Alteration Label

(101437-2), Standardized Allergenic (60682-2), Vaccine Label (53404-0), VFD

Type A Medicated Article Animal Drug Label (50575-0), VFD Type B Medicated

Feed Animal Drug Label (50572-7), VFD Type C Medicated Feed Animal Drug

Label (50571-9), or Animal Cells, Tissues, and Cell and Tissue Based Product

Label (98075-5), then the document contains data elements section as above.

29.2.1.2 Value of effective time is same as value of effective time in document

information.

29.2.2 Lot number

The label lot, or final container lot is the instance of the product, a portion of the fill

lot that is portioned out into individual containers.

</expirationTime>

29 Human and Animal Salvaged Drug Products

232

Validation Procedures

29.2.2.1 If the lot number is included Bulk Ingredient (53409-9), Bulk Ingredient –

Animal Drug (81203-2), Cellular Therapy (60684-8), Drug for Further

Processing (78744-0), Human OTC Drug Label (34390-5), Human Prescription

Drug Label (34391-3), License Blood Intermediates/Paste Label (53407-3),

Licensed Minimally Manipulated Cells Label (53408-1), Licensed Vaccine Bulk

Intermediate Label (53406-5), Non-Standardized Allergenic Label (53405-7),

OTC Animal Drug Label (50577-6), OTC Type A Medicated Article Animal

Drug Label (50576-8), OTC Type B Medicated Feed Animal Drug Label

(50574-3), OTC Type C Medicated Feed Animal Drug Label (50573-5), Plasma

Derivative (60683-0), Prescription Animal Drug Label (50578-4), Recombinant

Deoxyribonucleic Acid Construct Label (78745-7), Intentional Animal Genomic

Alteration Label (101437-2), Standardized Allergenic (60682-2), Vaccine Label

(53404-0), VFD Type A Medicated Article Animal Drug Label (50575-0), VFD

Type B Medicated Feed Animal Drug Label (50572-7), VFD Type C Medicated

Feed Animal Drug Label (50571-9), or Animal Cells, Tissues, and Cell and

Tissue Based Product Label (98075-5), then the only business operation is

salvage (C70827.)

29.2.2.2 There is one or more label lot elements

29.2.2.3 The lot has an id, and the general rules for lot numbers apply.

29.2.2.4 There is an id extension with the reported alphanumeric lot number string

29.2.2.5 Lot number string can contain digits, upper case letters and the characters “-”

and “/”.

29.2.2.6 There is a globally unique root OID

29.2.2.7 If the product item code is an NDC, then the globally unique root OID is formed

by using the fixed prefix "1.3.6.1.4.1.32366.1.2.10." followed by the full 10-

digit NDC code represented as a number without dashes and with initial zeroes

from the labeler code segment removed (e.g., "0001-0123-04" becomes

1012304).

29.2.2.8 If the product item code is an ISBT 128 code, then the globally unique root OID

is formed by using the fixed prefix “1.3.6.1.4.1.32366.1.2.13.” followed by a

decimal number value for the ISBT 128 facility identification number followed

by a period “.” and a decimal number value for the ISBT 128 product code, both

interpreted as a base 36 number with the digits 0-9 and A-Z, with the letter digits

having the value of 9 added to the ordinal letter position (A: 1 + 9 = 10, B = 2 +

9 = 11, ..., Z = 26 + 9 = 35), and ending with a period “.” and the 3

segment of

the ISBT 128 package item code without leading zeroes; e.g., ISBT 128 product

item code “W0123-E0404-03” with facility identification number “W0123”

SPL Implementation Guide with Validation Procedures v1

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interpreted in base 36: W = 23 + 9 = 32 × 36 + 0) × 36) + 1) × 36 + 2) × 36 + 3

= 53749083, and ISBT 128 product code “E0404” interpreted in base 36: E = 5

+ 9 = 14 × 36 + 0) × 36 + 4 ) × 36 + 0) × 36 + 4 = 23519812, and 3

segment

“03” without zeroes, resulting in

“1.3.6.1.4.1.32366.1.2.13.53749083.23519812.3”.

29.2.2.9 There is an expiration time with a high boundary.

29.2.2.10 Expiration time has at least the precision of month in the format YYYYMM

29.2.3 Container Data Elements

</quantity>

<formCode code="C43169" displayName="bottle"

codeSystem="2.16.840.1.113883.3.26.1.1"/>

</container>

Validation Procedures

29.2.3.1 There is a container reference.

29.2.3.2 There is a quantity with a numerator and denominator.

29.2.3.3 Numerator has a value greater than zero and a unit.

29.2.3.4 Numerator unit matches the dosing specification unit.

29.2.3.5 Denominator has value 1 and either no unit or unit “1”

29.2.3.6 The container form code and quantity is the same as the package of the product

as described in the listing for the package NDC.

29.2.3.7 There is a container packaged product code

29.2.3.8 Container packaged product item code is an NDC or based on ISBT-128.

29.2.3.9 There is a form code and display name

29.2.3.10 Code system for form code is 2.16.840.1.113883.3.26.1.1

29 Human and Animal Salvaged Drug Products

234

29.2.3.11 Display name matches form code

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30 FDA-Initiated Compliance Action – Drug Listing

Inactivation

30.1 Header

30.1.1 Document type

<code code="89600-1" codeSystem="2.16.840.1.113883.6.1"

displayName="FDA-Initiated Compliance Action Drug Registration and

Drug Listing Inactivation"/>

Validation Procedures

30.1.1.1 The document type is FDA-Initiated Compliance Action Drug Registration and

Drug Listing Inactivation (89600-1) or FDA-Initiated Compliance Action –

Drug Registration and Listing Inactivation - Animal Drug (99282-6).

30.1.1.2 If a document with the same set id has been previously submitted, then it is of

the same type.

30.1.2 Author information

FDA-initiated compliance action inactivation data is maintained by FDA:

<name>Food and Drug Administration</name>

Validation Procedures

30.1.2.1 Author information for drug listing inactivation is as above

30.1.2.2 The author is FDA.

30.1.2.3 There are no other author elements than id and name.

30.1.3 Reference Document

The subject of a drug listing inactivation is a referenced listing SPL document.

30 FDA-Initiated Compliance Action – Drug Listing Inactivation

236

...

</relatedDocument>

</document>

Validation Procedures

30.1.3.1 There is one reference document specified.

30.1.3.2 Type code attribute is as above.

30.1.3.3 There is no document id

30.1.3.4 There is a set id

30.1.3.5 Set id is a GUID

30.1.3.6 Reference document set id is the set id of a drug listing document.

30.1.3.7 If a drug listing inactivation file for the same reference document’s set id has

been previously submitted, then it is a prior version of this drug listing

inactivation document with the same set id.

30.1.3.8 If a document with the same set id has been previously submitted, then it is

associated with the same reference labeling set id.

30.1.3.9 If the document type is FDA-Initiated Compliance Action Drug Registration

And Drug Listing Inactivation (89600-1), then the reference document set id is

the set id of a human drug listing document.

30.1.3.10 If the document type is FDA-Initiated Compliance Action Drug Registration

And Drug Listing Inactivation - Animal Drug (99282-6), then the reference

document set id is the set id of an animal drug listing document.

SPL Implementation Guide with Validation Procedures v1

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30.2 Body

...

<code code="48780-1" codeSystem="2.16.840.1.113883.6.1"

displayName="SPL PRODUCT DATA ELEMENTS SECTION"/>

<text/>

Validation Procedures

30.2.1.1 There is one SPL Product Data Elements Section (48780-1.)

30.2.1.2 There are no subsections.

30.2.1.3 Validation procedures 2.2.1.2– 2.2.1.10 are applicable to FDA-Initiated

Compliance Action Drug Registration and Drug Listing Inactivation (89600-1),

and FDA-Initiated Compliance Action – Drug Registration and Listing

Inactivation - Animal Drug (99282-6).

30.2.1.4 There is no product code or any other product data elements except one flat list

of packages (asContent elements)

30.2.2 Inactivated or Reactivated Listing’s NDC(s)

Validation Procedures

30.2.2.1 There is at least one product package with item code.

30.2.2.2 Package item code system is NDC (2.16.840.1.113883.6.69).

30.2.2.3 NDC contains three segments divided by hyphens

30 FDA-Initiated Compliance Action – Drug Listing Inactivation

238

30.2.2.4 The NDC matches an NDC contained in the related listing document previously

submitted, except if an effective time high value (reactivation date) is present for

that NDC.

30.2.2.5 The same NDC is not mentioned more than once.

30.2.2.6 Product package has no other data elements than the package item code (NDC).

30.2.3 Compliance Action – Inactivation and Reactivation Status

The compliance action is the inactivation of a listing of a particular package. It has an

effective time with low (inactivation start) and high (inactivation end) date. If there is no

inactivation end date, the inactivation is sustained, when there is an inactivation end date,

the package is reactivated by FDA.

Each package that is being inactivated is listed directly under the manufacturedProduct

regardless of intermediary packages that may exist in the listing file.

</containerPackagedProduct>

<code code="C162847" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="Inactivated"/>

</effectiveTime>

</action>

</subjectOf>

Validation Procedures

30.2.3.1 There is one compliance action for each package.

30.2.3.2 Code is from the Regulatory Action list and display name matches the code.

30.2.3.3 There is an effective time with at least a low value (inactivation date)

30.2.3.4 The effective time low (inactivation date) and high boundary (reactivation date)

have at least the precision of day in the format YYYYMMDD

30.2.3.5 If there is an effective time high value (reactivation date), then it is not less than

the low value (inactivation date).

30.2.3.6 If there is an effective time high value (reactivation date), then it is not later than

the document effective time.

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30.2.3.7 If inactivation ending date is not present in the previous version of the file then

the product package can not be dropped from this file, except if the NDC has

also been dropped from the most recent version of the referenced listing file.

31 FDA-Initiated Compliance Action – Establishment Regis

tration Inac

240

31 FDA-Initiated Compliance Action – Establishment

Registration Inactivation

31.1 Header

31.1.1 Document type

<code code="89600-1" codeSystem="2.16.840.1.113883.6.1"

displayName="FDA-Initiated Compliance Action Drug Registration and

Drug Listing Inactivation"/>

Validation Procedures

31.1.1.1 The document type is FDA-Initiated Compliance Action Drug Registration and

Drug Listing Inactivation (89600-1) or FDA-Initiated Compliance Action –

Drug Registration and Listing Inactivation - Animal Drug (99282-6).

31.1.1.2 If a document with the same set id has been previously submitted, then it is of

the same type.

31.1.2 Author information

FDA-initiated compliance action inactivation data is maintained by FDA:

<name>Food and Drug Administration</name>

Validation Procedures

31.1.2.1 Author information for establishment registration inactivation is as above.

31.1.2.2 The author is FDA.

31.1.2.3 There are no other author elements than id and name.

31.1.3 Inactivated or Reactivated Establishments

SPL Implementation Guide with Validation Procedures v1

241

</assignedOrganization>

<code code="C162847" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="Inactivated"/>

Validation Procedures

31.1.3.1 There is an empty registrant level leading to the establishment.

31.1.3.2 The registrant level has no other element aside from the assignedEntity leading

to the establishment

31.1.3.3 There are one or more establishments.

31.1.3.4 The establishment level has no other element aside from the

assignedOrganization leading to the establishment and subjectOf to the

compliance action (characterstic).

31.1.3.5 Establishment is identified by one id, the DUNS Number.

31.1.3.6 DUNS number has root 1.3.6.1.4.1.519.1

31.1.3.7 DUNS number has a 9-digit extension

31.1.3.8 There is no other element besides the id for the DUNS Number.

31.1.3.9 The establishment DUNS Number occurs only once in this file

31.1.3.10 The establishment id (DUNS Number) has been submitted in a related

document of type “Establishment Registration” (51725-0).

31.1.3.11 If the document type is FDA-Initiated Compliance Action Drug Registration

And Drug Listing Inactivation (89600-1), then there is a business operation

except Medicated Animal Feed Manufacture (C84635) and Outsourcing Animal

Drug Compounding (C122061) in the previously submitted Establishment

Registration (51725-0).

31.1.3.12 If the document type is FDA-Initiated Compliance Action Drug Registration

And Drug Listing Inactivation - Animal Drug (99282-6), then there is a business

operation Analysis (C25391), API Manufacture (C82401), Label (C84732),

Manufacture (C43360), Medicated Animal Feed Manufacture (C84635) ,

Outsourcing Animal Drug Compounding (C122061), Pack (C84731), Particle

Size Reduction (C84386), Positron Emission Tomography Drug Production

31 FDA-Initiated Compliance Action –

Establishment Registration Inac

242

(C91403), Relabel (C73607), Repack (C73606), Salvage (C70827), Sterilize

(C84382), or Transfill (C125710) in the previously submitted Establishment

Registration (51725-0).

31.1.4 Compliance Action – Inactivation and Reactivation Status

The compliance action is the inactivation of the registration of a particular establishment.

It has an effective time with low (inactivation start) and high (inactivation end) date. If

there is no inactivation end date, the inactivation is sustained, when there is an

inactivation end date, the establishment is reactivated by FDA.

<code code="C162847" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="Inactivated"/>

</effectiveTime>

</characteristic>

</subjectOf>

Validation Procedures

31.1.4.1 There is one compliance action for each establishment.

31.1.4.2 Code is from the Regulatory Action list and display name matches the code.

31.1.4.3 There is an effective time with at least a low value (inactivation date)

31.1.4.4 The effective time low (inactivation date) and high boundary (reactivation date)

have at least the precision of day in the format YYYYMMDD

31.1.4.5 If there is an effective time high value (reactivation date), then it is not less than

the low value (inactivation date).

31.1.4.6 If there is an effective time high value (reactivation date), then it is not later than

the document effective time.

31.1.5 Reference Document

The subject of an establishment registration inactivation is a referenced establishment

registration SPL document.

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...

</relatedDocument>

</document>

Validation Procedures

31.1.5.1 There is one reference document specified.

31.1.5.2 Type code attribute is subject (SUBJ).

31.1.5.3 There is no document id

31.1.5.4 There is a set id

31.1.5.5 Set id is a GUID

31.1.5.6 Reference document set id is the set id of an establishment registration

document.

31.1.5.7 If an establishment registration inactivation file for the same reference

document’s set id has been previously submitted, then it is a prior version of this

establishment registration inactivation document with the same set id.

31.1.5.8 If a document with the same set id has been previously submitted, then it is

associated with the same reference labeling set id.

31.2 Body - Empty

Use an empty document body:

<text/>

31 FDA-Initiated Compliance Action –

Establishment Registration Inac

244

Validation Procedures

31.2.1.1 The document body is empty

SPL Implementation Guide with Validation Procedures v1

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32 Drug Interactions Indexing

32.1 Header

32.1.1 Document type

<code code="93723-5" codeSystem="2.16.840.1.113883.6.1"

displayName="INDEXING - DRUG INTERACTIONS"/>

Procedures

32.1.1.1 Document code is as above

32.1.1.2 If a document with the same set id has been previously submitted then it is of

the same type.

32.1.2 Author information

<time/>

<name>Food and Drug Administration</name>

32.1.2.1 Drug Interaction indexing content is maintained by FDA:

32.1.2.2 Author information for drug interactions indexing is as one of the above

32.1.3 Reference Labeling

The information about a Drug Interaction is derived from Reference Labeling. The

Reference Labeling is found in the SPL document submitted by the innovator, or, if

the innovator has stopped marketing the product, by a designated generic

manufacturer. The SPL document containing the Reference Labeling is specified

using its setId as follows:

...

</relatedDocument>

</document>

32 Drug Interactions Indexing

246

Validation Procedures

32.1.3.1 There is reference labeling specified.

32.1.3.2 Type code attribute is as above.

32.1.3.3 There is no document id

32.1.3.4 There is a set id

32.1.3.5 Set id is a GUID

32.1.3.6 Reference labeling set id is the set id of a drug listing document.

32.1.3.7 If a drug interactions indexing file for the same reference labeling set id has

been previously submitted, then it is a prior version of this indexing document

with the same set id.

32.1.3.8 If a document with the same set id has been previously submitted, then it is

associated with the same reference labeling set id.

32.2 SPL Body

Validation Procedures

32.2.1.1 The document body contains one or more sections

32.2.2 Sections

The interactions are grouped under the section headings where they have been

mentioned.

Validation Procedures

<code code="34068-7" displayName="Dosage & Administration"

codeSystem="2.16.840.1.113883.6.1"/>

<issue>

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32.2.2.1 Validation procedures for sections are as in Section 2.2.1 of this document.

32.2.2.2 Each section has one or more interactions.

32.2.3 Interaction

An drug interaction is an issue related to the administration of the reference label drug

document/section/subject2/substanceAdministration and then on the other hand is

related to the administration of another substance (drug). So the pattern is:

The labeled drug, which is the “consumable” of the first substance administration is

only implicitly given by the product(s) which are the subject of the reference label.

The administration of the “other” drug is also called the “contributing factor” to the

issue with the labeled drug.

<issue>

<code code="C54708" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="INTERACTION"/>

Validation Procedures

32.2.3.1 There is a code for interaction (C54708).

32.2.3.2 Code system is 2.16.840.1.113883.3.26.1.1.

32.2.3.3 Display name matches the code.

32.2.4 Contributing Factor

In drug-drug interactions, the contributing factor is the administration of another

drug. The other drug is “consumed” when administered, hence it is a “consumable”.

The other drug can be specified as any “administrable material” usually on the level

of a specific drug substance (ingredient), specified as a UNII code, or as a

pharmacologic class (see Section 8).

32 Drug Interactions Indexing

248

<issue>

<code code="80061L1WGD" displayName="CIMETIDINE"

codeSystem="2.16.840.1.113883.4.9"/>

Validation Procedures

32.2.4.1 There is a contributing factor, which is a substance administration.

32.2.4.2 Contributing factor substance administration has a consumable

32.2.4.3 Code system is UNII for specific drug substance or Med-RT or MeSH for

pharmacologic class.

32.2.4.4 If code system is UNII, then the code comes from the UNII list.

32.2.4.5 The UNII display name matches the code.

32.2.4.6 If code system is MED-RT (2.16.840.1.113883.6.345), then the code comes

from Med-RT subset for pharmacologic class indexing.

32.2.4.7 Med-RT display name matches the code.

32.2.4.8 If code system is MeSH (2.16.840.1.113883.6.177), then the code comes from

the MeSH subset for pharmacologic class indexing.

32.2.4.9 MeSH display name matches the code.

32.2.5 Consequence (Risk)

There are 3 kinds of interactions with regard to the consequence:

1. Pharmacodynamic interactions, where the consequence is some adverse

condition (medical problem).

2. Pharmacokinetic interactions, where the consequence is a change in

distribution, metabolization, or elimination.

3. Unspecified interactions, where the exact consequence is not described.

All three kinds of interactions have the same interaction/code, but are distinguished

by the the kind of consequence observation code, if any.

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<issue>

<code code="C54708" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="INTERACTION"/>

<risk>

<code code="C54386" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="Pharmacokinetic effect"/>

<value code="C54355" displayName="INCREASED DRUG LEVEL"

codeSystem="2.16.840.1.113883.3.26.1.1" xsi:type="CE"/>

Validation Procedures

32.2.5.1 There may be one or more consequences or none at all (unspecified

interactions).

32.2.5.2 There is a code for type of consequence, either pharmacokinetic effect (C54386,

with code system 2.16.840.1.113883.3.26.1.1) or medical problem (44100-6, of

code syetem 2.16.840.1.113883.6.1).

32.2.5.3 Display name for type of consequence matches the code

32.2.5.4 There is a consequence observation value.

32.2.5.5 Value xsi:type is as above

32.2.5.6 If consequence observation code is pharmacokinetic effect (C54386), then the

consequence value comes from Pharmacokinetic Effect List.

32.2.5.7 Consequence value (Pharmacokinetic Effect) display name matches the code.

32.2.5.8 If consequence observation code is medical problem (44100-6), then the

consequence value code system is SNOMED CT (2.16.840.1.113883.6.96).

32.2.5.9 If consequence value code system is SNOMED CT (2.16.840.1.113883.6.96),

then the code is 6 to 18 digits.

32.2.5.10 If consequence value code system is SNOMED CT (2.16.840.1.113883.6.96),

then the display name is the formal SNOMED CT name (fully specified name)

with the parenthesis indicating the kind of concept (finding, disorder, event).

33 National Clinical Trials Number Indexing

250

33 National Clinical Trials Number Indexing

33.1 Header

33.1.1 Document type

<code code="93372-1" codeSystem="2.16.840.1.113883.6.1"

displayName="INDEXING - NATIONAL CLINICAL TRIALS NUMBER"/>

Procedures

33.1.1.1 Document code is as above

33.1.1.2 If a document with the same set id has been previously submitted then it is of

the same type.

33.1.2 Author information

<time/>

<name>Food and Drug Administration</name>

33.1.2.1 NCT Indexing content is maintained by FDA:

33.1.2.2 Author information for NCT Indexing is as one of the above

33.1.3 Reference Labeling

The NCT Indexing information is derived from Clinical Studies Section (34092-7) of

Reference Labeling. The Reference Labeling is found in the SPL document submitted

by the innovator, or, if the innovator has stopped marketing the product, by a

designated generic manufacturer. The SPL document containing the Reference

Labeling is specified using its setId as follows:

...

</relatedDocument>

</document>

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Validation Procedures

33.1.3.1 There is reference labeling specified.

33.1.3.2 There is no document id

33.1.3.3 There is a set id

33.1.3.4 Set id is a GUID

33.1.3.5 Reference labeling set id is the set id of a drug listing document.

33.1.3.6 If a NCT indexing file for the same reference labeling set id has been previously

submitted, then it is a prior version of this indexing document with the same set

id.

33.1.3.7 If a document with the same set id has been previously submitted, then it is

associated with the same reference labeling set id.

33.2 Body

<code code="48779-3" codeSystem="2.16.840.1.113883.6.1"

displayName="SPL Indexing Data Elements Section"/>

33.2.1.1 If the document type is INDEXING - NATIONAL CLINICAL TRIALS NUMBER

(93372-1), then the document contains one SPL Indexing Data Elements Section

(48779-3) as above.

33.2.1.2 Value of effective time is same as value of effective time in document

information.

33.2.2 National Clinical Trials Number

</protocol>

</componentOf>

</substanceAdministration>

</subject2>

33.2.2.1 There is one or more NCT-References.

33.2.2.2 NCT Number has the prefix “NCT” followed by an 8-digit number.

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33.2.2.3 NCT-Reference id root is 2.16.840.1.113883.3.1077.

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34 [RESERVED]

35 Cosmetic Facility Registration

254

35 Cosmetic Facility Registration

Cosmetic facility registrations have only header information with a single registrant

organization and a facility to be registered or whose registration is to be updated.

Aside from the proper Cosmetic Facility Registration document type, four other

document types can be used for cosmetic facility registration submissions, i.e., the

Cosmetic Facility Registration - Amendment, Cosmetic Facility Registration -

Abbreviated Renewal, Cosmetic Facility Registration - Cancellation, and Cosmetic

Facility Registration - Biennial Renewal)

Table 9: Cosmetic Facility Registration Document Types

Code

Display Name

103573-2 Cosmetic Facility Registration Contains facility details, initial

submission.

X8888-1 Cosmetic Facility Registration - Amendment Contains facility details, update

for any changes.

X8888-2 Cosmetic Facility Registration - Abbreviated Renewal Does not contain facility details,

for biennial reneval if there is no

change.

X8888-3

Cosmetic Facility Registration - Cancellation

Does not contain facility details

X8888-4 Cosmetic Facility Registration - Biennial Renewal Contains facility details, for

biennial renewal that is not

abbreviated.

35.1 Header

35.1.1 Document type

<code code="103573-2" codeSystem="2.16.840.1.113883.6.1"

displayName="Cosmetic Facility Registration"/>

Validation Procedures

35.1.1.1 Document type is Cosmetic Facility Registration (103573-2), Cosmetic Facility

Registration - Amendment (X8888-1), Cosmetic Facility Registration -

Abbreviated Renewal (X8888-2), Cosmetic Facility Registration - Cancellation

(X8888-3), and Cosmetic Facility Registration - Biennial Renewal (X8888-4).

35.1.1.2 The effective time year matches the current year.

35.1.1.3 There is no title.

35.1.1.4 For a Cosmetic Facility Registration – Amendment (X8888-1), Cosmetic Facility

Registration – Abbreviated Renewal (X8888-2), Cosmetic Facility Registration

– Cancellation (X8888-3), and Cosmetic Facility Registration – Biennial

Renewal (X8888-4), the set id in this document is the same set id included in a

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previously submitted Cosmetic Facility Registration (103573-2), Cosmetic

Facility Registration – Amendment (X8888-1), or Cosmetic Facility Registration

– Biennial Renewal (X8888-4) with information about the facility.

35.1.1.5 If a document with the same set id as the one in this file has been previously

submitted, then the document type of the previously submitted file is Cosmetic

Facility Registration (103573-2), Cosmetic Facility Registration – Amendment

(X8888-1), or Cosmetic Facility Registration – Biennial Renewal (X8888-4).

35.1.1.6 Cosmetic Facility Registration – Biennial Renewal (X8888-4) and Cosmetic

Facility Registration – Abbreviated Renewal (X8888-2) documents are

submitted every 2 years, i.e., the year of their submission is more than one year

after the previous submission of any kind of Cosmetic Facility Registration

document.

35.1.2 Authorized Agent Information (Additional Contact)

<name>Cosmetic Company</name>

Validation Procedures

35.1.2.1 If the document type is Cosmetic Facility Registration - Abbreviated Renewal

(X8888-2), and Cosmetic Facility Registration - Cancellation (X8888-3), then

there is no authorized agent (additional contact).

35.1.2.2 If the document type is Cosmetic Facility Registration (103573-2), Cosmetic

Facility Registration - Amendment (X8888-1), or Cosmetic Facility Registration

– Biennial Renewal (X8888-4) , then there may be authorized agent information

(additional contact).

35.1.2.3 [RESERVED]

35.1.2.4 [RESERVED]

35.1.2.5 [RESERVED]

35.1.2.6 There may be one contact party (additional contact) as in Section 2.1.8.

35.1.2.7 Cosmetic Facility Registration has no labeler information.

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35.1.3 Submitter Name and Signature (Legal Authenticator)

The authorized individual may sign for the responsible organization as follows:

<noteText>The data and information in this submission have been

reviewed and, to the best of my knowledge, are certified to be true and

accurate. I agree to report changes to this information and renew as

required under section 607 of the Federal Food, Drug, and Cosmetic

Act.</noteText>

<signatureText mediaType=“text/plain”>P. Bauer</signatureText>

<name>Peter Bauer</name>

</assignedPerson>

35.1.3.1 There may be a signature (legalAuthenticator).

35.1.3.2 If present, the signature may contains a signing statement (noteText) exactly as

above.

35.1.3.3 If present, there is one signatureText element.

35.1.3.4 If present, the signatureText has mediaType “text/plain” and the electronic

signature in text content.

35.1.3.5 If present, the signature contains one assigned person (the signing person).

35.1.3.6 If present, assigned person has a name

35.1.3.7 If present, assigned person has only a name, no other element.

35.1.3.8 If present, the signature contains an empty representedOrganization element (the

signer signs for the responsible organization).

35.1.3.9 There is an time with at least the precision of day in the format YYYYMMDD

35.1.4 Facility Information

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<name>Facility Name</name>

<addr>

<city>Dublin</city>

<country code="IRL" codeSystem="1.0.3166.1.2.3">Ireland</country>

</addr>

Validation Procedures

35.1.4.1 If the document type is Cosmetic Facility Registration (103573-2), Cosmetic

Facility Registration -- Amendment (X8888-1), or Cosmetic Facility

Registration – Biennial Renewal (X8888-4), then there is one facility.

35.1.4.2 If the document type is Cosmetic Facility Registration - Abbreviated Renewal

(X8888-2) or Cosmetic Facility Registration - Cancellation (X8888-3), then

there is no facility information.

35.1.4.3 Facility has one name and one or two id elements, with the first id, the DUNS

number as in Section 2.1.5 but optional.

35.1.4.4 There is a second id (or if there is no DUNS number, the first id), the FEI with

root 2.16.840.1.113883.4.82 and 7- or 10-digit extension.

35.1.4.5 If present, the DUNS number along with the facility name and address

information match the DUNS number record in the Dun and Bradstreet

database.

35.1.4.6 The FEI number along with the facility name and address information match the

FEI number record previously assigned by the FDA.

35.1.4.7 Each facility has an address as in Section 2.1.6.

35.1.4.8 There is one contact party as in Section 2.1.8.

35.1.4.9 There is no assigned entity other than for US Agent.

35 Cosmetic Facility Registration

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35.1.5 Facility US Agent

<addr>

<country code="IRL"

codeSystem="1.0.3166.1.2.3">Ireland</country>

</addr>

<name>Simmons Reps Company</name>

</assignedOrganization>

<code code="C73330" codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="United States agent"/>

Validation Procedures

35.1.5.1 If the country for the facility is not “USA”, then there is one US agent.

35.1.5.2 US agent element has code, code system and display name are as above.

35.1.5.3 If the country for the facility is "USA", then there is no US agent.

35.1.5.4 US agent has a US telephone number (see 2.1.7.3 and following).

35.1.5.5 US agent has an e-mail address which is “N/A” if there is no email.

35.1.5.6 There is at most one US Agent.

35.1.6 Parent Company

...

<name>Parent Company Name</name>

</representedOrganization>

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35.1.6.1 If there is a parent company, there is just one name.

35.1.7 Small Business Designation

To indicate that the facility is a small business (except those which are not exempt

per section 612b of the FD&C Act), include the following characteristic element:

<code code="SPLSMALLBUSINESS"

codeSystem="2.16.840.1.113883.1.11.19255"/>

</characteristic>

</subjectOf>

35.1.7.1 Code and code system is as above (for SPLSMALLBUSINESS)

35.1.7.2 There is a Boolean value as above.

35.1.7.3 Value is “true”; to indicate not a small business omit the characteristic.

35.1.8 Facility Operation

Validation Procedures

35.1.8.1 There are no facility operation details (performance act definitions).

35.2 Body

If no cosmetic product listing information is included, use an empty document body:

<text/>

35 Cosmetic Facility Registration

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If cosmetic product information is included there is a document body with the product

data element section:

<code code="48780-1"

codeSystem="2.16.840.1.113883.6.1"

displayName="SPL product data elements section"/>

Validation Procedures

35.2.1.1 If the document is a Cosmetic Facility Registration – Abbreviated Renewal

(X8888-2), Cosmetic Facility Registration – Cancellation (X8888-3), then the

document body is empty

35.2.1.2 If the document is a Cosmetic Facility Registration (103573-2), Cosmetic

Facility Registration - Amendment (X8888-1), or Cosmetic Facility Registration

– Biennial Renewal (X8888-4), then there is a document body.

35.2.1.3 The document body contains one section

35.2.1.4 The one section contains the product data elements

35.2.2 Cosmetic Product

<code code="53-000000-000001"

codeSystem="2.16.840.1.113883.3.9848"/>

<name>Juvenia Soft</name>

<code code="01B" codeSystem="2.16.840.1.113883.6.345"

displayName="Baby products – Lotions, oils, powders, and creams"/>

The cosmetic listing number is included in any update after it has been assigned

subsequent to an initial cosmetic product listing submission.

Validation Procedures

35.2.2.1 There is a name, i.e., the brand name under which the cosmetic product is sold.

35.2.2.2 Markings such as ®, or ™ should not be included.

35.2.2.3 There are one or more cosmetic product category codes (asSpecializedKind

element) with a code (see Section 3.4.3).

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35.2.2.4 There are no other elements besides item code, name and cosmetic product type

(asSpecializedKind)

35.2.3 Responsible Person (Organization)

... name, cosmetic product type ...

</manufacturedProduct>

<name>Responsible Person (Organization) Name</name>

</manufacturerOrganization>

Validation Procedures

35.2.3.1 There is one responsible person (organization).

35.2.3.2 Responsible person (organization) has one name.

35.2.3.3 There are no other elements besides the name.

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36 Cosmetic Product Listing

Cosmetic product listings conform to 21 U.S.C. Sec. 607 as amended by the

Modernization of Cosmetics Regulation Act of 2022. Three document types can be

used for Cosmetic product listing, i.e., the Cosmetic, Cosmetic - Update , Cosmetic -

Abbreviated Renewal.

Table 10: Cosmetic Listing Document Types

Code

Display Name

103572-4

Cosmetic Product Listing

Contains cosmetic product details, initial submission.

X8888-5 Cosmetic – Update Contains cosmetic product details, update for any

changes.

X8888-6

Cosmetic – Abbreviated Renewal

Does not contains cosmetic product details

36.1 Header

36.1.1 Document Type

36.1.1.1 Document types is Cosmetic Product Listing (103572-4), Cosmetic – Update

(X8888-5), or Cosmetic – Abbreviated Renewal (X8888-6).

36.1.1.2 The effective time year matches the current year.

36.1.1.3 There is no title.

36.1.1.4 For a Cosmetic – Update (X8888-5), Cosmetic – Abbreviated Renewal (X8888-

6), the set id in this document is the same set id included in a previously

submitted document of type Cosmetic Product Listing (103572-4) or Cosmetic –

Update (X8888-5).

36.1.1.5 If a document with the same set id as the one in this file has been previously

submitted, then the document type of the previously submitted file is Cosmetic

Product Listing (103572-4) or or Cosmetic – Update (X8888-5).

36.1.2 Labeler (“responsible person” as per label)

<code code="..." codeSystem="2.16.840.1.113883.6.1"

displayName="..."/>

<name>Acme cosmetics company</name>

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<addr>

<streetAddressLine>1625 29th street</streetAddressLine>

<city>Camden</city>

</addr>

<name>Bob Jones</name>

</contactPerson>

</contactParty>

Validation Procedures

36.1.2.1 There is one labeler (“responsible person”), except if the document type is

Cosmetic – Abbreviated Renewal (X8888-6).

36.1.2.2 Responsible person has one name and may have one id element, the DUNS

number as in Section 2.1.5 but optional.

36.1.2.3 Responsible person has one telephone number (see 2.1.7.3 and following).

36.1.2.4 There may be one contact party (additional contact) as in Section 2.1.8.

36.1.2.5 Responsible person may have a parent company as per Section 35.1.6

<name>Parent Company Name</name>

</representedOrganization>

36.1.2.6 There is no other element besides id (the labeler’s DUNS Number), name,

telephone number, parent company (assignedEntity1), contact party, and

registrant (see next section).

36.1.3 Registrant

Details about the responsible person (organization) and its function as manufacturer,

packer, or distributor, and other facilities where the product is manufactured or

processed are reached through the otherwise empty “registrant” level:

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Validation Procedures

36.1.3.1 There is one assignedEntity/assignedOrganization element.

36.1.3.2 There is no other element besides facilities.

36.1.4 Responsible person further details

These include the type of business (manufacturer, packer, or distributor) and whether

it is a small business.

<code code="SPLSMALLBUSINESS"

codeSystem="2.16.840.1.113883.1.11.19255"/>

</characteristic>

</subjectOf>

<code code="C43360"

codeSystem="2.16.840.1.113883.3.26.1.1"

displayName="manufacture"/>

</actDefinition>

</assignedEntity>

Validation Procedures

36.1.4.1 If further details about the responsible person are provided, then they are in the

first assignedEntity element under the registrant level, with an empty

assignedOrganization element.

36.1.4.2 There may be a small business designation as in Section 35.1.7

36.1.4.3 There may be a performance actDefinition code as above.

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36.1.4.4 Code system is 2.16.840.1.113883.3.26.1.1

36.1.4.5 Code is manufacture (C43360), pack (C84731), or distribute (C201565)

36.1.4.6 Display name matches the code.

36.1.4.7 Responsible person further details has no operation product link.

36.1.4.8 Responsible person further details has at least a small business indicator or a

type of business code.

36.1.4.9 Responsible person further details has no other information besides a small

business indicator or a type of business code.

36.1.5 Facility information

All other assignedEntity elements under the registrant are facilities, with only an id

(the FEI) if the facility was required to be registered:

</assignedOrganization>

or with a name or address or FEI if, as a small business, the facility was not required

for being registered and has not been registered:

<name>Nimble Cosmetics Maker</name>

<addr>

<city>Dublin</city>

<country code="IRL" codeSystem="1.0.3166.1.2.3">Ireland</country>

</addr>

</assignedOrganization>

Facilities may also have a small business designation:

36 Cosmetic Product Listing

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<code code="SPLSMALLBUSINESS"

codeSystem="2.16.840.1.113883.1.11.19255"/>

</characteristic>

</subjectOf>

Validation Procedures

36.1.5.1 There are one or more facilities.

36.1.5.2 Facility may have a small business designation (except those which are not

exempt per section 612b of the FD&C Act) as in 35.1.7.

36.1.5.3 Facility may have an id, the FEI only.

36.1.5.4 The id is a FEI, with root 2.16.840.1.113883.4.82 and 7- or 10-digit extension.

36.1.5.5 The id (FEI) is not used for any other facilities in the file.

36.1.5.6 If the facility has no small business designation then there is an FEI.

36.1.5.7 If the facility has a small business designation then there may be an FEI.

36.1.5.8 If there is an id (FEI), then there may be a name or address.

36.1.5.9 If the facility is a small business (except those which are not exempt per section

612b of the FD&C Act) and there is no FEI, then there may be a name or

address.

36.1.5.10 If the facility has a small business designation, then the facility may have a

name .

36.1.5.11 If the facility has a small business designation, then the facility may have an

address as in Section 2.1.6 .

36.1.5.12 Facility (“assignedOrganization”) has no other element besides id (the FEI

Number) or name and address.

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36.1.6 Facility Product Link

The following example shows how the facilities are linked to particular products. It is

done by replicating the business operation (actDefinition) elements, and connecting

each with one product as shown below:

.. id or name and addr ...

</assignedOrganization>

The reference to the product occurs either by listing number if that has been assigned

(i.e. if the product data elements in this document already contain the listing number):

<code code="53-XXXXXX-XXXXXX"

codeSystem="2.16.840.1.113883.3.9848"/>

</manufacturedMaterialKind>

</manufacturedProduct>

</product>

or if the product listing number has not yet been assigned, then the reference is made

by name for the cosmetic product, as such name appears on the label:

<code/>

<name>Baby Shampoo</name>

</manufacturedMaterialKind>

</manufacturedProduct>

</product>

Note that the schema still requires an empty code element.

36 Cosmetic Product Listing

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Validation Procedures

36.1.6.1 There are one or more performance/actDefinition elements.

36.1.6.2 The performance/actDefinition element has one product reference.

36.1.6.3 There is either a Cosmetic Product Listing Number, or a name (but not both).

36.1.6.4 Product reference refers to one listed product or part product either by name or

by product listing number.

36.1.6.5 If the facility has no small business designation, then there is an active facility

registration for this facility with a cosmetic product.

36.1.6.6 Each listed product is linked from at least one facility.

36.1.7 Submitter Name and Signature (Legal Authenticator)

The authorized individual may sign for the responsible organization as follows:

<noteText>The data and information in this submission have been

reviewed and, to the best of my knowledge, are certified to be true and

accurate. I agree to report changes to this information as required under

section 607 of the Federal Food, Drug, and Cosmetic Act.</noteText>

<signatureText mediaType=“text/plain”>P. Bauer</signatureText>

<name>Peter Bauer</name>

</assignedPerson>

36.1.7.1 There may be a signature (legalAuthenticator).

36.1.7.2 If present, the signature may contain a signing statement (noteText) exactly as

above.

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36.1.7.3 If present, there is one signatureText element.

36.1.7.4 If present, the signatureText has mediaType “text/plain” and the electronic

signature in text content.

36.1.7.5 If present, the signature contains one assigned person (the signing person).

36.1.7.6 If present, assigned person has a name

36.1.7.7 If present, assigned person has only a name, no other element.

36.1.7.8 If present, the signature contains an empty representedOrganization element (the

signer signs for the responsible organization).

36.1.7.9 There is an time with at least the precision of day in the format YYYYMMDD.

36.2 Body

36.2.1 Required Sections

Validation Procedures

36.2.1.1 If the document is a Cosmetic – Abbreviated Renewal (X8888-6), then the

document body is empty

36.2.1.2 If the document is a Cosmetic Product Listing (103572-4), Cosmetic – Update

(X8888-5), then there is a document body.

36.2.1.3 The document body contains one section, the product data element section

36.2.1.4 The section contains the product data elements

36.2.2 Cosmetic Product

<code code="53-000000-000001"

codeSystem="2.16.840.1.113883.3.9848"/>

<name>Juvenia Soft</name>

<code code="01B" codeSystem="2.16.840.1.113883.6.345"

displayName="Baby products – Lotions, oils, powders, and creams"/>

<ingredient>...

36 Cosmetic Product Listing

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The cosmetic listing number is included in any update after it has been assigned

subsequent to an initial cosmetic product listing submission.

Validation Procedures

36.2.2.1 If a product by the same name has been included in the previous version of the

cosmetic product listing, then the assigned Cosmetic Product Listing Number is

included.

36.2.2.2 Code system is 2.16.840.1.113883.3.9848 (Cosmetic Product Listing Number).

36.2.2.3 The Cosmetic Product Listing Number has the format 53-XXXXXX-XXXXXX

where X stands for any digit 0 to 9.

36.2.2.4 The Cosmetic Product Listing Number has previously been assigned by the

FDA.

36.2.2.5 [RESERVED]

36.2.2.6 The product names in the listing are unique.

36.2.2.7 If the products names in the listing are not unique, then there is also

distinguishing information for identification purposes.

36.2.2.8 If the product names in the listing are not unique and the distinguishing

information is confidential, then the distinguishing information is in parenthesis.

36.2.2.9 If the product names in the listing are unique, then there may be also

distinguishing information for identification purposes.

36.2.2.10 If the product names in the listing are unique and distinguishing information is

confidential, then the distinguishing information is in parenthesis.

36.2.2.11 There are one or more cosmetic product category codes (asSpecializedKind

element) with a code (see Section 3.4.3).

36.2.2.12 Name, ingredients (including fragrance, color, and flavor) match the name for

the cosmetic product, as such name appears on the label previously assigned to

this listing number and the responsible person’s name included in the previous

version of this file.

36.2.2.13 Cosmetic product category matches the cosmetic product category previously

assigned to this listing number.

36.2.2.14 There are one or more ingredients (as per Section 3.4.4)

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36.2.2.15 There may be a web page link as per Section 3.4.6.2

36.2.2.16 There may be a professional use indicator as per Section 3.4.8.

36.2.2.17 There may be a label image as per Section 3.4.9.

0 Appendix

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Appendix

List of Tables

Table 1: Marketing Category and Product Type ............................................................... 37

Table 2: Equivalence Codes .............................................................................................. 41

Table 3: Miscellaneous Identifier Types ........................................................................... 43

Table 4: Characteristic codes and code systems. .............................................................. 66

Table 5: Conventions for expressing strength .................................................................. 75

Table 6: Characteristic codes and code systems. .............................................................. 95

Table 7: Document Types for Labeling , Listing, and other Product Submissions ........ 105

Table 8: Document Types and Marekting Categories for which even completed product

listings should have establishments. ............................................................................... 109

Table 9: Cosmetic Facility Registration Document Types ............................................. 254

Table 10: Cosmetic Listing Document Types ................................................................ 262