Guidance for Industry 

Providing Regulatory 

Submissions in Electronic 

Format – Drug Establishment 

Registration and Drug Listing 

DRAFT GUIDANCE

This guidance document is being distributed for comment purposes only. 

Although you can comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure 

that the agency considers your comment on this draft guidance before it begins work on the final 

version of the guidance, submit written or electronic comments on the draft guidance within 60 

days after date of publication in the FEDERAL REGISTER. 

Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug 

Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be 

identified with the docket number listed in the notice of availability that publishes in the Federal 

Register. Submit electronic comments to http://www.regulations.gov. 

For questions regarding this draft document contact Lonnie Smith, 301-594-0011. 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Office of the Commissioner 

 

July 2008 

Electronic Submission 
Contains Nonbinding Recommendations 

Draft — Not for Implementation 

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Providing Regulatory 

Submissions in Electronic 

Format – Drug Establishment 

Registration and Drug Listing 

Additional copies are available from: 

Office of Training and Communication 

Division of Drug Information, HFD-240 

Center for Drug Evaluation and Research 

Food and Drug Administration 

5600 Fishers Lane 

Rockville, MD 20857 

(Tel) 301-827-4573 

 http://www.fda.gov/cder/guidance/index.htm 

and/or 

 Office of Communication, Training and 

Manufacturers Assistance, HFM-40 

Center for Biologics Evaluation and Research 

 Food and Drug Administration 

1401 Rockville Pike, Rockville, MD 20852-1448 

 http://www.fda.gov/cber/guidelines.htm 

(Tel) 800-835-4709 or 301-827-1800

and/or 

Communications Staff, HFV-12 

Center for Veterinary Medicine 

Food and Drug Administration 

7500 Standish Place, 

Rockville, MD 20855 

(Tel) 240-276-9300 

http://www.fda.gov/cvm/guidance/guidance.htm 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Office of the Commissioner 

July 2008 

Electronic Submission 
Contains Nonbinding Recommendations 

Draft — Not for Implementation 

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TABLE OF CONTENTS 

I. INTRODUCTION............................................................................................................. 1

II. BACKGROUND ............................................................................................................... 2

III. VOLUNTARY PILOT PROGRAM AND TRANSITION ........................................... 2

IV. DRUG ESTABLISHMENT REGISTRATION AND DRUG LISTING 

INFORMATION FOR ELECTRONIC SUBMISSION ............................................... 4

A. Drug Establishment Registration .................................................................................................4

1. Who must register and when?..........................................................................................................4

2. What information is required?.........................................................................................................4

3. What additional information is recommended?...............................................................................5

B. Drug Listing....................................................................................................................................5

1. Who must list and when? .................................................................................................................5

2. What information is required?.........................................................................................................6

3. What additional information is recommended?...............................................................................6

V. CREATING THE DRUG ESTABLISHMENT REGISTRATION AND DRUG 

LISTING FILE FOR ELECTRONIC SUBMISSION .................................................. 8

A. Structured Product Labeling ........................................................................................................8

B. Terminology ...................................................................................................................................8

1. Unique Ingredient Identifiers (UNII)...............................................................................................9

2. Data Universal Numbering System (D-U-N-S®) Number...............................................................9

3. Other terminology............................................................................................................................9

C. Submission and FDA Validation of Electronic Drug Establishment Registration and 

 Drug Listing Information..............................................................................................................9

D. Technical Assistance ....................................................................................................................10

VI. IMPLEMENTATION .................................................................................................... 10
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Guidance for Industry1

Providing Regulatory Submissions in Electronic Format – 

Drug Establishment Registration and Drug Listing 

86 This draft guidance, when finalized, will represent the Food and Drug Administration's (FDA's) current 

87 thinking on this topic. It does not create or confer any rights for or on any person and does not operate to 

88 bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of 

89 the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA 

90 staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call 

91 the appropriate number listed on the title page of this guidance. 

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I. INTRODUCTION 

This is one in a series of guidance documents intended to assist persons making regulatory 

submissions to FDA in electronic format. This guidance explains how to participate in a 

voluntary Pilot Program that has been designed to assist manufacturers with transitioning from 

paper-based to electronic submissions of drug establishment registration and drug listing 

information and to test the performance of FDA’s electronic system for this type of submission. 

The guidance, along with accompanying technical documents, explains what registration and 

listing information (including labeling) to submit and describes how to submit the information 

electronically in Structured Product Labeling (SPL) files, using a defined terminology. FDA 

intends to update regularly guidance documents on electronic submissions to reflect the evolving 

nature of the technology and the experience using this technology. 

FDA's guidance documents, including this guidance, do not establish legally enforceable 

responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should 

be viewed only as recommendations, unless specific regulatory or statutory requirements are 

cited. The use of the word should in Agency guidances means that something is suggested or 

recommended, but not required. 

II. BACKGROUND 

Requirements for drug establishment registration and drug listing are set forth in section 510 of 

the Federal Food, Drug, and Cosmetic Act (the Act) and section 351 of the Public Health Service 

1

 The Office of Critical Path Programs, Office of the Commissioner, Food and Drug Administration prepared this 

guidance document in cooperation with the Center for Drug Evaluation and Research, the Center for Biologics 

Evaluation and Research, and the Center for Veterinary Medicine. 

 

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Act (the PHS Act), and 21 CFR Part 207.2 Drug establishment registration and drug listing 

information is currently submitted in paper form using Form FDA 2656 (Registration of Drug 

Establishment/Labeler Code Assignment), Form FDA 2657 (Drug Product Listing), and Form 

FDA 2658 (Registered Establishments’ Report of Private Label Distributors).

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The information collected during drug establishment registration and drug listing is fundamental 

to FDA’s mission to protect the public health, including surveillance for serious adverse drug 

reactions, inspection of facilities used for drug manufacturing and processing, and monitoring 

drug products imported into the United States. Comprehensive, accurate, and up-to-date 

information is important for conducting these activities with efficiency and effectiveness. 

Electronic drug establishment registration and drug listing using a computerized system would 

lead to significant improvements in the timeliness and accuracy of the information received 

compared with the current paper-based system. This automated process can function most 

efficiently and effectively when the information is provided in a standardized format using 

defined terminology. 

Section 510 of the Act and 21 CFR part 207, subject to certain limited exceptions, require 

owners and operators of establishments (registrants) upon first engaging in the manufacture, 

preparation, propagation, compounding, or processing of drugs, (including human drugs, 

veterinary drugs, and biological drug products) to register their establishments and submit listing 

information for all drugs and biological drug products in commercial distribution. Registrants 

are also required to submit, on or before December 31 of each year, updates to registration 

information for their establishments.4

 Registrants must, at the time of annual registration, also 

submit required listing information.5

 Additionally, registrants are required to update listing 

information in June and December of each year to include information for drugs and biological 

drug products that have not been previously listed.6

 Certain changes to information for 

previously listed drugs and biological drug products must also be submitted in June and 

December of each year.7 

Under section 351(j) of the PHS Act, the Act and regulations promulgated under the Act apply to 

biological drug products. 

Changes in the Act, resulting from enactment of the Food and Drug Administration Amendments 

Act of 2007 (Public Law 110-85) (FDAAA),8 require that drug establishment registration and 

2

 This guidance document does not apply to establishment registration and product listing information required 

solely under 21 CFR part 607, 21 CFR 807, and 21 CFR part 1271. 

3

 These forms are currently available at http://www.fda.gov/opacom/morechoices/fdaforms/default.html. 

4

 Section 510(b)(1) of the Act. 

5

 Section 510(j)(1) of the Act. 

6

 Section 510(j)(2)(A) of the Act. 

7

 Section 510(j)(2) of the Act. 

8

 Signed into law on September 27, 2007. 

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drug listing information be submitted electronically unless a waiver is granted. Before the 

enactment of FDAAA, section 510(p) of the Act expressly provided for electronic submission of 

drug establishment registration information upon a finding that electronic receipt was feasible, 

and section 510(j) of the Act provided that drug listing information be submitted in the form and 

manner prescribed by FDA. Section 224 of FDAAA, which amends section 510(p) of the Act, 

now expressly requires electronic drug listing in addition to drug establishment registration. 

FDA intends to exercise enforcement discretion and does not intend to take action to enforce this 

electronic submission requirement, but rather intends to pilot voluntary electronic submission 

during a transition period as discussed below. 

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Efforts are under way at FDA to transition from a paper-based to an electronic submission 

environment, making it possible for FDA to begin to receive drug establishment registration and 

drug listing information electronically. FDA is creating the voluntary Pilot Program to assist 

manufacturers to transition from paper-based to electronic submissions and to assist the Agency 

in testing the performance of its systems for processing electronic submissions.9 This guidance 

and accompanying technical documents lay out the procedures for those wishing to participate in 

the Pilot Program. Any persons subject to the provisions in section 510 of the Act and 21 part 

207 may participate in this Pilot Program.10 FDA intends to only accept electronic drug 

establishment registration and drug listing information beginning June 1, 2009 (unless a waiver 

is granted.) 

As another part of the transitioning effort, FDA issued a proposed rule that would amend 21 CFR 

part 207 to require electronic submission of drug establishment registration and drug listing 

information, among other provisions such as certain changes to the National Drug Code system 

and requiring the appropriate NDC on the drug label (71 FR 51276, August 29, 2006). FDA is 

still in the process of considering comments submitted on the proposed rule and intends to revise, 

reissue, or revoke this guidance document as appropriate for consistency with the final rule, 

when issued. 

III. VOLUNTARY PILOT PROGRAM AND TRANSITION 

FDA is launching a Pilot Program that enables industry to begin voluntarily submitting drug 

establishment registration and drug listing information in electronic format. This guidance 

document describes how to transition from submitting drug establishment registration and drug 

listing information on paper forms to submitting the information using the SPL format, an 

electronic format that FDA can process, review, and archive. FDA is adopting the use of 

9

 When we are ready to receive a particular submission type in electronic format only, we generally identify it in the 

public docket 92S-0251. Under 21 CFR part 11, you then have the option of providing that submission type in 

electronic format in a manner that FDA can adequately process, review, and archive. See also Guidance for 

Industry: Part 11, Electronic Records; Electronic Signatures -- Scope and Application (August 2003). 

10 See footnote 2. 

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extensible markup language (XML) files in a standard Structured Product Labeling (SPL)11

format as the standard format for the exchange of drug establishment registration and drug listing 

information. Information in a properly created and complete SPL file can be processed in 

minutes. In addition, the use of SPL with defined terminology allows for more precise and 

accurate registration and listing information. Timely and accurate information will enhance 

FDA’s efforts to help ensure the integrity of the drug supply and protect the public health. 

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This guidance, and accompanying technical documents, describes how to electronically create 

and submit SPL files using a defined terminology for drug establishment registration and drug 

listing information (including labeling as specified under 21 CFR 207.25). Technical 

specifications are provided in the following technical documents: 

• Structured Product Labeling Implementation Guide for FDA Drug Establishment 

Registration and Drug Listing 

• Instructions for Using Electronic Drug Establishment Registration and Drug Listing 

XForms 

• FDA’s Structured Product Labeling Validation Procedures for Electronic Drug 

Establishment Registration and Drug Listing 

These documents are on the FDA Website at http://www.fda.gov/oc/datacouncil/spl.html and are 

discussed in section V of this document. 

IV. DRUG ESTABLISHMENT REGISTRATION AND DRUG LISTING 

INFORMATION FOR ELECTRONIC SUBMISSION 

The following information in this section should be submitted to FDA in the SPL file format as 

described in section V of this document. 

A. Drug Establishment Registration 

1. Who must register and when? 

The owner or operator of an establishment entering into the manufacture, preparation, 

propagation, compounding, or processing (which includes, among other things, repackaging and 

relabeling) of a drug or drugs12 and not exempt under section 510(g) of the Act or subpart B of 

21 CFR part 207, must register the establishment with FDA within 5 days after beginning the 

operation. (21 CFR 207.21(a)). Alternatively, if the establishment has not previously entered 

into such an operation, the owner or operator must register within 5 days after submitting a drug 

application, biological license application, or medicated feed mill license application. Owners or 

operators must renew their registration information annually. (21 CFR 207.21(a)). 

Foreign establishments that engage in the manufacture, preparation, propagation, compounding, 

or processing (which includes, among other things, repackaging and relabeling) of a drug that is 

imported or offered for import into the United States (and that are not exempt) must upon first 

11 SPL standard is a Health Level Seven, Inc. standard for the exchange of product information using extensible 

markup language (XML). 

12 Means both human, including biological drug products, and animal drugs. 

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engaging in such activity immediately register and register annually thereafter (see section 510(i) 

of the Act and 21 CFR 207.40).

Amendments to drug establishment registration must be submitted in accordance with 21 CFR 

207.26. 

2. What information is required? 

Drug establishment registration information has historically been submitted on Form FDA 2656. 

Section 510 of the Act and 21 CFR Part 207 set forth the registration information required to be 

submitted by domestic and foreign drug establishments (see sections 510(b), (c), (d), and (i) of 

the Act and 21 CFR 207.22(a), 207.25(a), 207.26, and 207.40). Such drug establishment 

information includes, for example, the name and address of each drug establishment, all trade 

names used by the establishment, the kind of ownership or operation (i.e., individually owned, 

partnership or corporation), and the name of the owner or operator. Under 21 CFR 207.40(c), 

foreign registrants must provide certain additional information specific to their establishments. 

For example, a foreign registrant must submit the name, address, and phone number of its United 

States agent and, under section 510(i)(1)(A) of the Act, the name of each importer that is known 

to the establishment (this means each U.S. company or individual in the United States that is an 

owner, consignee, or recipient, of the foreign establishment’s drug, that is imported into the 

United States. An importer does not include the consumer or patient who ultimately purchases, 

receives, or is administered the drug, unless the foreign establishment ships the drug directly to 

the consumer or patient.); and the name of each person who imports or offers for import (this 

means the name of each agent, broker, or other entity, other than a carrier, that the foreign drug 

establishment uses to facilitate the import of their drug into the United States). Section 510(p) of 

the Act, as amended by FDAAA, now requires drug establishment registrations to be submitted 

electronically unless a waiver is granted. 

3. What additional information is recommended? 

Registrants have also voluntarily submitted additional drug establishment registration 

information on Form FDA 2656. For electronic submission, registrants are encouraged to also 

submit the following information in their SPL file: 

• Official contact’s name, mailing address, telephone number(s), and email address; 

• Each registered establishment’s telephone number(s); and 

• The type of operation(s) performed at each registered establishment. 

To facilitate correspondence between registrants and FDA, foreign registrants should submit the 

email address for the U.S. agent, and the telephone number(s) and email address for the importer 

and person who imports or offers for import described in section IV.A.2 of this document. 

B. Drug Listing 

1. Who must list and when? 

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Registrants, which do not include those exempt under 21 CFR 207.10, must submit the initial 

listing information for all drugs

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13 in commercial distribution at the time of their initial 

registration of their establishment(s). (21 CFR 207.21(a)). 

Because FDA does not accept drug establishment registration information from private label 

distributors, private label distributors may request their own NDC Labeler Code and elect to 

submit drug listing information to FDA. (21 CFR 207.20(b)). In such instances, at the time of 

submitting or updating drug listing information, private label distributors must certify to the 

registered establishment(s) that manufactured, prepared, propagated, compounded or processed 

(which includes, among other things, repackaging and relabeling) the listed drug(s) that the drug 

listing submission was made. (21 CFR 207.20(b)). 

Registrants (and, if applicable, private label distributors) must update their drug listing 

information, and include drugs that have subsequently been introduced for commercial 

distribution and, therefore, have not previously been listed.14 Any updates must be submitted 

every June and December.15 However, registrants (and, if applicable, private label distributors) 

are encouraged to submit updates through the registration and listing system more frequently as a 

change occurs, including updates to labeling required to be submitted. (21 CFR 207.21(b), 

207.22(b), 207.25, and 207.30) 

2. What information is required? 

Listing information has historically been submitted on Form FDA 2657. Section 510 of the Act 

and 21 CFR Part 207 set forth the drug listing information required to be submitted by domestic 

and foreign drug establishments (see section 510(j) of the Act and 21 CFR 207.25(b) and (c), 

207.30, 207.31, and 207.40). Such drug listing information includes, for example, the listed 

drug’s established name and proprietary name, application number (if any), and the NDC 

number. Labels, labeling, and/or advertisements are also required to be submitted as specified in 

section 510(j) of the Act and 21 CFR 207.25(b) and 207.40. Section 510(p) of the Act, as 

amended by FDAAA, now requires drug listing, including updates, to be submitted 

electronically unless a waiver is granted. 

3. What additional information is recommended? 

a. Additional information on Form FDA 2657 

Registrants and, if applicable, private label distributors have also voluntarily submitted 

additional drug listing information on Form FDA 2657 and Form FDA 2658. For electronic 

submission, registrants are encouraged to submit the following information in their SPL file: 

• Name of establishment(s) manufacturing or processing the listed drug and the type of 

operation(s) performed; 

13 Includes combination products and their constituents (see 21 CFR part 3). 

14 Section 510(j)(2) of the Act. 

15 Section 510(j)(2) of the Act. 

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• Route(s) of administration; 

• Inactive ingredients and strength or amount; 

• Marketing information (e.g., category, start/stop date); 

• Information related to the application or OTC monograph citation number (e.g., type and 

year of approval); and 

• Package size and type. 

b. Manufacturer’s Information for Voluntary Reporting of Adverse Drug 

Reactions 

In providing the labeling as specified under 21 CFR 207.25, FDA recommends for 

manufacturers with a Web site for voluntary reporting of adverse drug reactions that the 

registrant provide the manufacturer’s telephone number and URL address that appears on the 

label (21 CFR 201.57(a)(11)). 

c. Site-specific D-U-N-S® Number16

FDA recommends that the D-U-N-S® Number (as described in section V.B.2 of this document) 

should be submitted for each site-specific entity (e.g., the registrant, establishments, U.S. agent, 

importer). Submitting the site-specific D-U-N-S® Number for an entity would provide by 

reference to the number certain business information for that entity, e.g., trade names used by the 

entity, addresses, additional ownership information, such as the name of each partner or the 

name of each corporate officer and director, and the state of incorporation otherwise required for 

drug establishment registration. 

d. NDC Product Code for a Source Drug Repacked or Relabeled 

Repackers and relabelers may submit the NDC Product Code for the source drug that is repacked 

or relabeled to reference previously submitted manufacturing establishment information. 

e. Reference Drug 

In rare situations, the strength of the drug is based on a reference drug. In such cases, the 

registrant (and, if applicable, private label distributor) are encouraged to include the reference 

drug used as a basis for the strength of the listed drug to avoid confusion. 

g. Distinctive Characteristics of Certain Listed Drugs 

Registrants are encouraged to provide the following characteristics for the listed drug, when 

applicable. Registrants have previously provided these characteristics voluntarily as helpful 

information to the public for the safe and effective use of their products. 

16 D-U-N-S® Numbers are proprietary to and controlled by Dun & Bradstreet (D&B). D&B grants a customer a 

non-exclusive, perpetual, limited license to use D-U-N-S® Numbers solely for identification purposes and only for 

the customer’s internal business use. Where practicable, the customer will refer to the number as a “D-U-N-S® 

Number” and state that D-U-N-S is a registered trademark of D&B. 

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• Flavor 

When applicable, the registrants (and, if applicable, private label distributor) may provide the 

flavor as a unique distinguishing characteristic of the listed drug. (Registrants have previously 

provided this information on Form FDA 2657 as an ingredient.) 

• Color 

For liquid dosage forms, the registrant (and, if applicable, private label distributor) may provide 

the color as a unique distinguishing characteristic. This may be useful when the color of a 

solution is confused for contamination or a change in color may indicate contamination. 

• Image 

For solid oral dosage forms, the registrant (and, if applicable, private label distributor) may 

submit an image of the actual dosage form. This information is helpful to the consumer in 

determining the correctly dispensed drug. The registrant should obtain instructions on obtaining 

the image and the proper format in the SPL file by following the instructions for technical 

assistance in section V.D of this document. 

h. Confidentiality Flag 

Registrants (and, if applicable, private label distributor) may identify an inactive ingredient or 

the registrant’s business relationship with an establishment that they view as confidential when 

submitting registration and listing information. Pursuant to a Freedom of Information Act 

request or on our own initiative, FDA will ultimately make determinations as to whether drug 

establishment registration and drug listing information can be disclosed to the public pursuant to 

the Trade Secrets Act, the Freedom of Information Act, and other applicable law (e.g., section 

510(f) of the Act and 21 CFR 207.37). 

V. CREATING THE DRUG ESTABLISHMENT REGISTRATION AND DRUG 

LISTING FILE FOR ELECTRONIC SUBMISSION 

A. Structured Product Labeling 

Structured Product Labeling (SPL) is the standard that will be used for the exchange of drug 

establishment registration and drug listing information and is based on the Health Level Seven 

(HL7) version 3 Reference Information Model (RIM) and the Clinical Document Architecture 

(CDA). The SPL file used for information exchange is written in XML. 

FDA intends to use SPL release 4 (SPLr4) for electronic submissions of drug establishment 

registration and drug listing information. The technical details on using SPLr4 for registration 

and listing are available in the document Structured Product Labeling Implementation Guide for 

FDA Drug Establishment Registration and Drug Listing (SPL Implementation Guide). 

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FDA has been accepting SPL files for certain product information since 2004, and vendors have 

provided solutions for creating SPL files ranging from basic software tools to comprehensive 

information management systems. Additionally, FDA has collaborated with GlobalSubmit on 

software to create SPL files based on XForms technology. Information on using the XForms is 

available in the document Instructions for Using Electronic Drug Establishment Registration 

and Drug Listing XForms. 

These documents are on the FDA web site at: http://www.fda.gov/oc/datacouncil/spl.html. 

B. Terminology 

FDA has been working with a number of organizations to develop and maintain terminology 

used for submitting drug establishment registration and drug listing information electronically. 

Although many terms and codes are already available, FDA is continuously updating this 

terminology and adding additional codes. Information on the organizations that maintain the 

terminology for submitting drug establishment registration and drug listing information 

electronically and how to obtain the terms and codes used for electronic drug registration and 

listing follows. 

1. Unique Ingredient Identifiers (UNII) 

UNII is the defined terminology FDA uses for ingredients. FDA along with United States 

Pharmacopeia (USP) maintains the UNII using the FDA Substance Registration System. These 

names and identifiers are accessible through USP Web site at http://www.usp.org and 

publications, the FDA Web site at http://www.fda.gov/oc/datacouncil and the NCI Thesaurus 

Web site at http://evs.nci.nih.gov. Additional ingredient identifiers may be requested through 

FDA by sending a request to spl@fda.hhs.gov. In submitting your request, identify in the subject 

line of the email the Center responsible for regulating the listed drug, i.e., Center for Drug 

Evaluation and Research, Center for Biologics Evaluation and Research, or the Center for 

Veterinary Medicine. 

2. Data Universal Numbering System (D-U-N-S®) Number 

Dun & Bradstreet assigns and maintains a database of the D-U-N-S® Numbers, which serve as 

unique identifiers of business entities. Upon application, each business entity (e.g., registrant, 

establishment, importer, US agent) is assigned a distinct site-specific 9-digit D-U-N-S® Number. 

If the D-U-N-S® Number for a location has not been assigned, a business may obtain one for no 

cost directly from Dun & Bradstreet (http://www.dnb.com). 

3. Other terminology 

FDA collaborates with the National Cancer Institute Enterprise Vocabulary Services (NCI EVS) 

to maintain terminology for dosage form, routes of administration, package types, DEA 

schedule, product color, product shape, flavors, business operations, marketing categories and 

equivalence codes. These terminologies are located in the NCI Thesaurus and may be accessed 

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Draft — Not for Implementation 

through the NCI EVS Web site at http://evs.nci.nih.gov and FDA web site at 

http://www.fda.gov/oc/datacouncil/spl.html. Additional terms and codes for use in registration 

and listing may be requested though FDA by sending a request to spl@fda.hhs.gov. 

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The Regenstrief Institute17 maintains a number of different terminologies used in electronic drug 

establishment registration and drug listing including: document types, section headings, and units 

of measure. These terminologies are located in the Logical Observation Identifiers Names and 

Codes (LOINC) and Unified Codes for Units of Measure (UCUM) systems. Both of these 

terminologies are available at http://www.regenstrief.org and at other locations. Additional terms 

and codes may be requested through FDA by sending a request to spl@fda.hhs.gov. 

C. Submission and FDA Validation of Electronic Drug Establishment 

Registration and Drug Listing Information 

The SPL file should be created following the technical specifications in the SPL Implementation 

Guide and other information found in this document. Other resources for creating the SPL file, 

including a link to a user-friendly software tool (XForms), are also available.18 Once the SPL 

file is created, it can then be submitted (uploaded) by following the instructions for the FDA 

Electronic Submissions Gateway (ESG), including digital certification.19 

FDA uses a computer system for processing the SPL files using controlled terminology. The 

computer system automatically checks the SPL files for certain errors, mistakes and omissions 

prior to entering the information into FDA systems. FDA will work with companies to help 

correct identified problems in order to complete the registration and listing process. Information 

on the details used in checking SPL files for electronic drug establishment registration and drug 

listing are in the document FDA’s Structured Product Labeling Validation Procedures for 

Electronic Drug Establishment Registration and Drug Listing.

20 This document is on the FDA 

web site at: http://www.fda.gov/oc/datacouncil/spl.html. 

D. Technical Assistance 

For technical problems or questions, or technical assistance with creating SPL files, send an 

email to spl@fda.hhs.gov. 

17 The Regenstrief Institute is an internationally recognized informatics and healthcare research organization. 

18 See http://www.fda.gov/oc/datacouncil/spl.html for additional resources, terminology, and data standards 

regarding the SPL files. See http://www.fda.gov/oc/datacouncil/xforms.html for information on the user-friendly 

software tool. 

19 See http://www.fda.gov/esg/default.htm for information on other resources and using the FDA ESG. 

20 This document is used by FDA and describes FDA’s computer instructions for automating the validation of 

submitted SPL files containing registration and listing information. 

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483 VI. IMPLEMENTATION 

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As previously discussed, FDA intends to transition its paper-based drug establishment 

registration and drug listing to an electronic process. During the transition period, FDA intends 

to continue to accept paper forms.21 However, beginning June 1, 2009, FDA plans to complete 

the voluntary Pilot Program and, unless a waiver is granted, expects to receive all drug 

establishment registration and drug listing information in electronic format22 only. 

FDA envisions few instances in which electronic submission of registration and listing 

information will not be reasonable and, thus, does not anticipate the need to grant many 

waivers.23 

21 During the voluntary Pilot Program, the registrant should submit the drug establishment registration and drug 

listing information either electronically or using the Forms FDA 2656, FDA 2657, and FDA 2658, but not both. 

22 Section 510(p) of the Act. 

23 Section 510(p) of the Act. 

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