Federal Register: NOTICES Draft Guidance for Industry: [Docket No. FDA-2005-N-0464] (formerly Docket No. 2005N-0403)

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

Docket ID: [Docket No. FDA-2005-N-0464] (formerly Docket No. 2005N-0403)

NOTICE: NOTICES

ACTION: Draft Guidance for Industry:

DOCUMENT ACTION: Notice.

SUBJECT CATEGORY: Draft Guidance for Industry on Providing Regulatory Submissions in Electronic Format--Drug Establishment Registration and Drug Listing; Availability

DATES: Although you can comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that the agency considers your comments on this draft guidance before it begins work on the final version of the guidance, submit written or electronic comments on the draft guidance, including comments regarding proposed collection of information, by September 9, 2008.

DOCUMENT SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled ``Providing Regulatory Submissions in Electronic FormatDrug Establishment Registration and Drug Listing.'' This draft guidance document establishes a Pilot Program for industry to voluntarily submit drug establishment registration and drug listing information in an electronic format that FDA can process, review, and archive. The document provides guidance on what required and FDArecommended information related to drug establishment registration and drug listing to submit and on how to electronically prepare and submit the information to FDA.

SUMMARY: Providing Regulatory Submissions in Electronic Format-Drug Establishment Registration and Drug Listing; Availability,

SUPPLEMENTAL INFORMATION

I. Background

In the Federal Register of August 29, 2006 (71 FR 51276), FDA issued a proposed rule that would revise part 207 (21 CFR part 207) (hereinafter referred to as ``the 2006 proposed rule''). This rule, when finalized, will fully implement electronic drug establishment registration and drug listing. Subsequent to the publication of the proposed rule, the U.S. Congress enacted the Food and Drug Administration Amendments Act of 2007 (FDAAA) (Public Law 11085) . FDAAA amended section 510 of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 360) (at section 510(p)) to explicitly require the electronic submission by domestic and foreign establishments of registration and listing information (including the submission of updated information) required under section 510 of the act, unless the Secretary of Health and Human Services grants a request for a waiver if use of electronic means is not reasonable for the person requesting the waiver. 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. To assist in complying with this new statutory provision, and to test FDA systems for processing such submissions, FDA is announcing a voluntary Pilot Program for electronically submitting drug establishment registration and drug listing information and the availability of a draft guidance for industry entitled ``Providing Regulatory Submissions in Electronic FormatDrug Establishment Registration and Drug Listing.''

The information collected during drug establishment registration and drug listing information is fundamental to many processes FDA uses for protecting the public health, including surveillance for serious drug adverse reactions, inspection of facilities used for drug manufacturing and processing, and monitoring drug products imported into the United States. Comprehensive, complete, uptodate information is critical for conducting these activities with efficiency and effectiveness. Electronic drug establishment registration and drug listing using computer systems to automate this process will lead to significant improvements in the timeliness and accuracy of the information over a paperbased system. This automation can be accomplished most efficiently and effectively when the information is provided in a standardized format using defined terminology.

FDA is adopting the use of extensible markup language (XML) files in a standard Structured Product Labeling (SPL)\1\ format as the standard format for the exchange of drug establishment registration and drug listing information. Information in a properly created SPL file can be processed in minutes. In addition, the use of SPL files with defined terminology will facilitate the receipt of more precise and accurate information than was the case with paper submissions. Timely and accurate product information will enhance FDA's efforts to help ensure the integrity of the drug supply and protect the public health. \1\ SPL standard is a Health Level Seven, Inc., standard for the exchange of product information using extensible markup language (XML).

The draft guidance explains how to transition from submitting the required information on paper\2\ to submitting the required information using the SPL standard, an electronic format that FDA can process, review, and archive. The draft guidance also describes how to voluntarily submit additional useful, but not required, information that currently is often included by industry in paper submissions. The draft guidance, along with accompanying technical documents made available on FDA's Website\3\, 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 Sec. 207.25) required under section 510 of the act and part 207.\4\ In addition to comments on the draft guidance, FDA also is requesting comments on the adequacy and usefulness of the technical documents that are available on FDA's Web site.
\2\ Drug establishment registration and drug listing information is currently submitted in paper format 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). These forms are currently available at http://www.fda.gov/opacom/morechoices/ fdaforms/fdaforms.html.
\3\ These technical documents are currently available at http:// www.fda.gov/oc/datacouncil/spl.html.
\4\ Under section 351(j) of the Public Health Service Act, the act and regulations issued under the act apply to biological products. However, this guidance document does not apply to establishment registration and product listing information required solely under 21 CFR parts 607, 807, and 1271.

With publication of the guidance, FDA is launching a voluntary Pilot Program that will enable industry to begin submitting drug establishment registration and drug listing information in electronic format. FDA plans to complete the voluntary Pilot Program and begin receiving drug establishment registration and drug listing information only electronically and in SPL format (including labeling) beginning June 1, 2009, unless a waiver is granted. Based on comments received on the draft guidance and information obtained during the voluntary Pilot Program, FDA intends to issue a final guidance before June 1, 2009.

FDA is still in the process of considering comments submitted on the 2006 proposed rule. FDA intends to revise, reissue, or revoke any final guidance as appropriate, to ensure consistency with the final rule.

This draft guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the agency's current thinking on the electronic submission of drug establishment registration and drug listing. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations.

II. Comments

Interested persons may submit to the Division of Dockets Management (see ADDRESSES) written or electronic comments regarding this document. Submit a single copy of electronic comments or two paper copies of any mailed comments, except that individuals may submit one copy. Comments are to be identified with the docket number found in brackets in the heading of this document. Received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.

Please note that on January 15, 2008, the FDA Division of Dockets [[Page 39966]]
Management Web site transitioned to the Federal Dockets Management System (FDMS). FDMS is a Governmentwide electronic docket management system. Electronic comments or submissions will be accepted by FDA only through FDMS at http://www.regulations.gov. III. Paperwork Reduction Act of 1995

Under the Paperwork Reduction Act (44 U.S.C. 35013520) (the PRA), Federal agencies must obtain approval from the Office of Management and Budget (OMB) for each collection of information they conduct or sponsor. ``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes agency requests or requirements that members of the public submit reports, keep records, or provide information to a third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal agencies to provide a 60day notice in the Federal Register concerning each proposed collection of information before submitting the collection to OMB for approval. To comply with this requirement, FDA is publishing notice of the proposed collection of information set forth in this document.

With respect to the following collection of information, FDA invites comments on these topics: (1) Whether the proposed collection of information is necessary for the proper performance of FDA's functions, including whether the information will have a practical utility; (2) the accuracy of FDA's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility, and clarity of the information to be collected; and (4) ways to minimize the burden of the collection on respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology.

Title: Draft Guidance for Industry on Providing Regulatory Submissions in Electronic FormatDrug Establishment Registration and Drug Listing.

Description of Respondents: Respondents to this collection of information are foreign and domestic owners and operators of establishments that engage in the manufacture, preparation, propagation, compounding, or processing (which includes, among other things, repackaging and relabeling) of a drug or drugs\5\ and that are not exempt under section 510(g) of the act or subpart B of part 207 (registrants).
\5\ Means both human, including biological products, and animal drugs.

A. Reporting Burden

The draft guidance describes how to electronically create and submit SPL files using defined terminology for establishment registration and drug listing information (including labeling). Most information is already required to be submitted under section 510 of the act, section 351 of the Public Health Service Act, and part 207.

Drug establishment registration and drug listing information and updates to such information, required under part 207, and certain additional recommended information are 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) (collectively referred to as FDA Forms; 72 FR 67733, November 30, 2007).

In addition to the information collected by the FDA Forms (72 FR 67733, November 30, 2007), the draft guidance addresses electronic submission of other required information as follows:

For registered foreign drug establishments, the name, address, and phone number of its U.S. agent (Sec. 207.40(c));

The name of each importer that is known to the establishment (the 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 the patient) (section 510(i)(1)(A) of the act); and

The name of each person who imports or offers for import (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(i)(1)(A) of the act).

FDA also is recommending the voluntary submission of the following additional information, when applicable:

To facilitate correspondence between foreign
establishments and FDA, 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 their drug;

In providing the labeling as specified under Sec. 207.25, for manufacturers with a Web site for voluntary reporting of adverse drug reactions, the manufacturer's telephone number and URL address that appear on the label under 21 CFR 201.57(a)(11);

A sitespecific DUNS[reg] Number\6\ for each entity (e.g., the registrant, establishments, U.S. agent, importer); \6\ A D&B[reg] DUNS[reg] Number is a unique ninedigit
sequence recognized as the universal standard for identifying and keeping track of over 100 million business worldwide. Submitting the sitespecific DUNS[reg] Number for an entity would provide by reference to the number certain business information for that entity, e.g., address, parentage.

The NDC product code for the source drug that is repacked or relabeled;

A reference drug if used as a basis for the strength of the listed drug;

Distinctive characteristics of certain listed drugs, i.e., the flavor, the color, and image of the actual solid dosage form; and

Registrants may indicate that they view as confidential the registrant's business relationship with an establishment, or an inactive ingredient.

In addition to the collection of information, there is additional burden for the following activities:

Preparing a standard operating procedure (SOP) for the electronic submission of drug establishment registration and drug listing information;

Creating the SPL file, including accessing and reviewing the technical specifications and instructional documents provided by FDA (accessible at http://www.fda.gov/oc/datacouncil/spl.html);

Reviewing and selecting appropriate terms and codes used to create the SPL file (accessible at http://www.fda.gov/oc/ datacouncil/spl.html);

Obtaining the digital certificate used with FDA's electronic submission gateway (ESG) and uploading the SPL file for submission (accessible at http://www.fda.gov/esg/default.htm); and

Requests for waivers from the electronic submission process as described in the draft guidance.

B. Burden Estimates

Reporting BurdenThe estimates for the number of respondents, annual frequency per response, and total annual responses indicated in table 1 of this document are based on our current estimates of the number of registrants and the number of submissions using the FDA Forms (OMB Control No. 09100045). FDA estimates that it would take an additional 2 hours per response (in addition to the estimated 2.5 hours per
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response for registering, labeler code requests, listing, and providing updates to the information approved under OMB Control No. 09100045) for the collection of information not currently submitted using the FDA Forms, and to create and upload the SPL file. FDA anticipates that the hours per response will decrease over time due to the flexibility of submitting information for registering multiple establishments or listing multiple drugs in one SPL file instead of submitting individual FDA Forms, and increasing familiarity with the use of the standards and terminology for creating the SPL file.

In certain cases, if it is unreasonable to expect a person to submit registration and listing information electronically, FDA may grant a waiver from the electronic format requirement. Because registrants will only need a computer and access to the Internet, FDA envisions few instances in which electronic submission of registration and listing information will not be reasonable for the person requesting the waiver and, thus, is estimating that FDA would grant one waiver annually. We estimate that a onetime burden for requesting a waiver would be an hour of time for a midlevel manager to draft, approve, and mail a letter.

Recordkeeping BurdenIn table 2 of this document, FDA estimates that 3,295 (39 + 3,256) respondents would expend a onetime burden of approximately 40 hours in preparing, reviewing, and approving an SOP for creating and uploading the SPL file; and an estimated 1 hour annually to maintain the SOP as needed.

FDA estimates the information collection burden, in addition to that approved under OMB Control No. 09100045 as follows:
Table 1.Estimated Annual Reporting Burden\1\ No. of Annual Frequency Total Annual Hours per Activity Respondents per Response Responses Response Total Hours New 39 14.72 574 2 1,148 registrations
, including
new labeler
code requests
Annual updates 3,256 2.99 9,735 2 19,470 of
registration
information
New drug 1,567 6.57 10,295 2 20,590 listings
New listings 146 10.06 1,469 2 2,938 for private
label
distributors
June and 1,677 11.21 18,799 2 37,598 December
updates of
all drug
listing
information
Waiver 1 1 1 1 1 requests
Total 81,745 \1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
Table 2.Estimated Annual Recordkeeping Burden\1\ No. of Annual Frequency Total Annual Activity Recordkeepers per Recordkeeping Records Hours per Record Total Hours Onetime 3,295 1 3,295 40 131,800 preparation of
SOP
SOP maintenance 3,295 1 3,295 1 3,295 Total 135,095 \1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

C. Costs Associated with Electronic Submission

There are no capital costs or operating and maintenance costs associated with the transition from paper to electronic submissions. To create an SPL file and submit it to FDA, a registrant would need the following tools: A computer, appropriate software, access to the Internet, knowledge of terminology and standards, and access to FDA's Electronic Submission Gateway (ESG).

Registrants (and most individuals) have computers and Internet access available for their use. If a business does not have an available computer or access to the Internet, free use of computers and Internet are usually available at public facilities, e.g., a community library; or they may request a waiver from submitting the information electronically.

Software is necessary to create a ``document.'' The SPL file or ``document'' may be created internally by a business with experience with SPL, or a business may use a userfriendly software (XForms)\7\ available at no cost for industry use. In addition to the software, FDA also provides technical assistance, and other resources, terminology, and data standards regarding SPL files.\8\
\7\ See http://www.fda.gov/oc/datacouncil/xforms.html. \8\ See http://www.fda.gov/oc/datacouncil/spl.html.

Once the SPL file is created, the registrant would upload the file through the ESG. A digital certificate is needed to use the ESG. The digital certificate binds together the owner's name and a pair of electronic keys (a public key and a private key) that can be used to encrypt and sign documents. However, a small fee of up to $20.00 is charged for the digital certificate and the registrant may need to renew the
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certificate not less than annually. FDA is not calculating this small fee as cost of doing business because it is less than or equal to the biannual courier costs the registrant incurs for paper submissions. IV. Electronic Access

Persons with access to the Internet may obtain the draft guidance at http://www.fda.gov/cber/ guidelines.htm, http://www.fda.gov/cvm/guidance/guidance.html, and http://www.regulations.gov.

Dated: July 3, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E815801 Filed 71008; 8:45 am]
BILLING CODE 416001S

FOR FURTHER INFORMATION CONTACT Lonnie Smith, Office of Critical Path Programs (HF18), Office of the Commissioner, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 3015940011.