[Federal Register Volume 73, Number 134 (Friday, July 11, 2008)]
[Notices]
[Pages 39964-39968]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-15801]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Draft Guidance for Industry on Providing Regulatory Submissions 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

AGENCY:  Food and Drug Administration, HHS.

ACTION:  Notice.

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SUMMARY:  The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance for industry entitled ``Providing 
Regulatory Submissions in Electronic Format--Drug 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 This draft guidance document 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 FDA-recommended 
information related to drug establishment registration and drug listing 
to submit and on how to electronically prepare and submit the 
information to FDA.

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this draft guidance before it begins work on the final version of the 
guidance, submit written or electronic comments on the draft guidance, 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.

ADDRESSES:  Submit written requests for single copies of the draft 
guidance to the Office of Critical Path Programs (HF-18), Office of the 
Commissioner, Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857. Send one self-addressed adhesive label to assist 
the office in processing your requests.

[[Page 39965]]

The draft guidance may also be obtained by mail by calling the Office 
of Critical Path Programs at 301-827-1512. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the draft guidance 
document.
    Submit written comments on the draft guidance to the Division of 
Dockets Management (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments 
to http://www.regulations.gov.

FOR FURTHER INFORMATION CONTACT:  Lonnie Smith, Office of Critical Path 
Programs (HF-18), Office of the Commissioner, Food and Drug 
Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-594-0011.

SUPPLEMENTARY 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 110-85) . 
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 
Format--Drug 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, up-to-date 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 paper-based 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.
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    \1\ SPL standard is a Health Level Seven, Inc., standard for the 
exchange of product information using extensible markup language 
(XML).
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    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.
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    \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.
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    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 Government-wide 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. 3501-3520) (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 60-day 
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 Format--Drug 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).
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    \5\ Means both human, including biological products, and animal 
drugs.
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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 e-mail address for the U.S. agent, and the 
telephone number(s) and e-mail 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 site-specific D-U-N-S[reg] Number\6\ for each entity 
(e.g., the registrant, establishments, U.S. agent, importer);
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    \6\ A D&B[reg] D-U-N-S[reg] Number is a unique nine-digit 
sequence recognized as the universal standard for identifying and 
keeping track of over 100 million business worldwide. Submitting the 
site-specific D-U-N-S[reg] Number for an entity would provide by 
reference to the number certain business information for that 
entity, e.g., address, parentage.
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     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 Burden--The 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. 0910-0045). 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. 0910-0045) 
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 one-time burden for requesting a 
waiver would be an hour of time for a mid-level manager to draft, 
approve, and mail a letter.
    Recordkeeping Burden--In table 2 of this document, FDA estimates 
that 3,295 (39 + 3,256) respondents would expend a one-time 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. 0910-0045 as follows:

                                 Table 1.--Estimated Annual Reporting Burden\1\
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                      No. of         Annual Frequency       Total Annual        Hours per
   Activity        Respondents         per Response          Responses           Response         Total Hours
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New                            39                 14.72                574                  2              1,148
 registrations
 , including
 new labeler
 code requests
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Annual updates              3,256                  2.99              9,735                  2             19,470
 of
 registration
 information
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New drug                    1,567                  6.57             10,295                  2             20,590
 listings
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New listings                  146                 10.06              1,469                  2              2,938
 for private
 label
 distributors
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June and                    1,677                 11.21             18,799                  2             37,598
 December
 updates of
 all drug
 listing
 information
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Waiver                          1                  1                     1                  1                  1
 requests
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Total                                                                                                     81,745
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


                               Table 2.--Estimated Annual Recordkeeping Burden\1\
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                         No. of        Annual Frequency     Total Annual
     Activity        Recordkeepers    per Recordkeeping       Records       Hours per  Record     Total Hours
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One-time                       3,295                  1              3,295                 40            131,800
 preparation of
 SOP
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SOP maintenance                3,295                  1              3,295                  1              3,295
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Total                                                                                                    135,095
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\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 user-friendly 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\
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    \7\ See http://www.fda.gov/oc/datacouncil/xforms.html.
    \8\ See http://www.fda.gov/oc/datacouncil/spl.html.
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    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/cder/guidance/index.htm, 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. E8-15801 Filed 7-10-08; 8:45 am]
BILLING CODE 4160-01-S