[Federal Register: July 11, 2008 (Volume 73, Number 134)]
[Notices]
[Page 39964-39968]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr11jy08-50]
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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Draft Guidance for Industry on Providing Regulatory Submissions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availability of a draft guidance for industry entitled ``Providing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 This draft guidance document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this draft guidance before it begins work on the final version of the
guidance, submit written or electronic comments on the draft guidance,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ADDRESSES: Submit written requests for single copies of the draft
guidance to the Office of Critical Path Programs (HF-18), Office of the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The draft guidance may also be obtained by mail by calling the Office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INFORMATION section for electronic access to the draft guidance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Submit written comments on the draft guidance to the Division of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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/opacom/morechoices/fdaforms/fdaforms.html.
\3\ These technical documents are currently available at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=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
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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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/oc/datacouncil/spl.html);
Reviewing and selecting appropriate terms and codes used
to create the SPL file (accessible at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/oc/datacouncil/xforms.html.
\8\ See http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/index.htm, http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cber/guidelines.htm, http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cvm/guidance/guidance.html, and
http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=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