[Federal Register Volume 74, Number 5 (Thursday, January 8, 2009)]
[Notices]
[Pages 816-819]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-108]


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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)


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Draft Guidance for 
Industry on Providing Regulatory Submissions in Electronic Format--Drug 
Establishment Registration and Drug Listing

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that a 
proposed collection of information has been submitted to the Office of 
Management and Budget (OMB) for review and clearance under the 
Paperwork Reduction Act of 1995.

DATES: Fax written comments on the collection of information by 
February 9, 2009.

ADDRESSES:  To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
FAX: 202-395-6974, or e-mailed to <a href="/cdn-cgi/l/email-protection#57383e2536082422353a3e24243e383917383a357932382779303821"><span class="__cf_email__" data-cfemail="204f4952417f5355424d495353494f4e604f4d420e454f500e474f56">[email protected]</span></a>. All 
comments should be identified with the OMB control number 0910-0045. 
Also include the FDA docket number found in brackets in the heading of 
this document.

FOR FURTHER INFORMATION CONTACT: Jonna Capezzuto, Office of Information 
Management (HFA-710), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857, 301-796-3794.

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

Draft Guidance for Industry on Providing Regulatory Submissions in 
Electronic Format--Drug Establishment Registration and Drug Listing; 
Availability; Registration of Producers of Drugs and Listing of Drugs 
in Commercial Distribution--(OMB Control Number 0910-0045--Amendment)

    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\1\ and that are 
not exempt under section 510(g) of the Federal Food, Drug, and Cosmetic 
Act (the act) or subpart B of part 207 (21 CFR part 207) (registrants).
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    \1\ 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 Structured Product Labeling (SPL) files using defined code sets 
and codes 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

[[Page 817]]

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:
    <bullet> For registered foreign drug establishments, the name, 
address, and telephone number of its U.S. agent (Sec.  207.40(c));
    <bullet> 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
    <bullet> 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:
    <bullet> 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;
    <bullet> A site-specific D-U-N-S[reg] Number\2\ for each entity 
(e.g., the registrant, establishments, U.S. agent, importer);
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    \2\ 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 businesses 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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    <bullet> The National Drug Code product code for the source drug 
that is repacked or relabeled;
    <bullet> Distinctive characteristics of certain listed drugs, i.e., 
the flavor, the color, and image of the actual solid dosage form; and
    <bullet> 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:
    <bullet> Preparing a standard operating procedure (SOP) for the 
electronic submission of drug establishment registration and drug 
listing information;
    <bullet> 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);
    <bullet> Reviewing and selecting appropriate terms and codes used 
to create the SPL file (accessible at http://www.fda.gov/oc/datacouncil/spl.html);
    <bullet> 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
    <bullet> 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 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 code sets and codes 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.
    In the Federal Register of July 11, 2008 (73 FR 39964), FDA 
published a notice of availability of the draft guidance document 
providing a 60-day public comment period on the information collection 
provisions. Nineteen comments were received of which four remarked on 
the information collection. Thereafter, in the Federal Register of 
October 23, 2008 (73 FR 63158), FDA published a 30-day notice 
responding to the comments submitted on the proposed collection of 
information and announced that the proposed collection of information 
had been submitted to OMB. In response to a request by OMB, FDA is 
republishing the 30-day notice responding to comments and announcing 
the submission of the proposed collection of information to OMB.
    (Comment 1) On the topic 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, one 
comment agreed that the proposed collection of information is necessary 
for us to perform its functions and is consistent with the provisions 
of the Food and Drug Administration Amendments Act of 2007 (Public Law 
110-85). The comment continued to say that the information is also 
necessary to support the transition from paper format to electronic 
format, and that the additional information requested by us is logical 
and reasonable and is not an undue burden.
    (Response) We appreciate the support and concurrence of the 
comment.
    (Comment 2) On the topic whether the accuracy of FDA's estimate of 
the burden of the proposed collection of information, including the 
validity of the methodology and assumptions used, one comment stated 
that we underestimated the effort to prepare, review, approve, 
implement and maintain internal SOPs for electronic submission of drug 
establishment registration and drug listing information because of the 
following reason. Particularly for most large companies, drug 
establishment registration and drug listing information (currently 
submitted in paper format under 21 CFR 207.22)

[[Page 818]]

and content of labeling (currently submitted in electronic format under 
21 CFR 314.50(l)(1)(i)) are handled by completely different functional 
experts and/or departments in the companies. To coordinate these 
processes, additional time is needed to define new procedures and 
interactions that cross functional departments and possibly 
international groups. Therefore, large companies will expend more than 
40 hours to prepare, review, approve, implement and maintain SOPs.
    Another comment asserts that the hours per response in table 1 are 
underestimated if the estimate accounts for the time required to become 
familiar with the Structured Product Labeling (SPL) standard.
    (Response) In estimating hours per record in table 2 of this 
document, we considered the various sizes of entities affected and 
proposed an average number of hours per activity. For example, the 
estimated 40 hours per record are based on smaller entities requiring 
approximately 20 hours per record and larger entities requiring 
approximately 60 hours per record. Therefore, because the comment did 
not provide a revised estimate, we are maintaining an estimate of 40 
hours per record, which is consistent with preparing SOPs for paper 
format submissions and also includes coordination efforts.
    Regarding the comment on underestimating the hours per response in 
table 1, the software designed to create the SPL files, the step-by-
step instructions in the technical guides, and our technical assistance 
email address are provided by us for the purpose of minimizing the need 
to learn the SPL standard before submitting information electronically.
    In this document, we are correcting an error in table 1 under the 
hours per response column. Although the written description of the 
burden added 2 hours to the existing 2.5 hours approved by OMB under 
Control Number 0910-0045 (for a total of 4.5 hours), 4.5 hours was not 
correctly reproduced in table 1. The total hours column is also 
adjusted to reflect this correction.
    (Comment 3) On the topic of 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, one comment encouraged us to continue the availability of 
Xforms at no cost for industry to use as a software tool for the 
creation of SPL. The comment also requested that we continue this 
practice as technology evolves and provide support for this tool.
    (Response) We appreciate the encouragement of the comment and will 
consider the request to continue the practice and provide support as 
technology evolves.
    (Comment 4) Two comments did not agree with our statement that 
there are no capital or operating and maintenance costs associated with 
the collection of information. The comments explained that some 
companies may choose alternative tools to the Xform software or work 
with external conversion providers, which may involve the purchase and 
maintenance of software plus the use of internal information technology 
personnel for installation, configuration and maintenance. These 
comments further stated that these costs are significant and need to be 
considered in the overall cost for industry to comply with the 
electronic submission requirement.
    (Response) As the comments stated, companies may choose to use 
alternative tools or work with external conversion providers. We do not 
disagree. However, we have made every effort to eliminate costs to 
industry to comply with the statutory requirement to electronically 
submit drug establishment registration and drug listing information.
    We also received comments that were specifically related to the 
technical documents referenced in the draft guidance. Although these 
comments are not directly related to the draft guidance document that 
contains the information collection, we will consider the comments when 
reviewing the technical documents for revision.
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1.--Estimated Annual Reporting Burden\1\
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                                          Annual Frequency per     Total Annual        Hours per
     Activity        No. of Respondents         Response             Responses          Response     Total Hours
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New registrations,                    39                 14.72                 574              4.5      2,583
 including new
 labeler code
 requests
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Annual updates of                  3,256                  2.99               9,735              4.5     43,807.5
 registration
 information
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New drug listings                  1,567                  6.57              10,295              4.5     46,327.5
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New listings for                     146                 10.06               1,469              4.5      6,610.5
 private label
 distributors
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June and December                  1,677                 11.21              18,799              4.5     84,595.5
 updates of all
 drug listing
 information
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Waiver requests                        1                     1                   1                1          1
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Total               ....................  ....................  ..................  ...............    183,924
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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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                                       Annual Frequency per     Total Annual        Hours per
    Activity     No. of Recordkeepers      Recordkeeping           Records            Record        Total Hours
----------------------------------------------------------------------------------------------------------------
One-time                        3,295                     1               3,295               40      131,800
 preparation of
 SOP
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[[Page 819]]

 
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 
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)\3\ available at no cost for industry use. In addition to the 
software, FDA also provides technical assistance, and other resources, 
code sets and codes, and data standards regarding SPL files.\4\
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    \3\ See http://www.fda.gov/oc/datacouncil/xforms.html.
    \4\ 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 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.

    Dated: December 22, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E9-108 Filed 1-7-09; 8:45 am]
BILLING CODE 4160-01-S


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