[Federal Register Volume 73, Number 206 (Thursday, October 23, 2008)]
[Pages 63158-63161]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-25338]



Food and Drug Administration

[Docket No. FDA-2005-N-0464]

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of Management and Budget Review; Comment Request; Draft Guidance for 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.


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 
November 24, 2008.

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 [email protected]. 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Draft Guidance for Industry on Providing Regulatory Submissions in 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 at 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 or subpart B of 21 CFR part 207 (part 207) (registrants).

    \1\ Means both human, including biological products, and animal 

A. Reporting Burden

    The draft guidance describes how to electronically create and 
submit Structured Product Labeling (SPL) files using defined 
terminology for establishment registration and drug

[[Page 63159]]

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, 
    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 telephone 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\2\ for each entity 
(e.g., the registrant, establishments, U.S. agent, importer);

    \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.

     The National Drug Code 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 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.
    In the Federal Register of July 11, 2008 (73 FR 39964), FDA 
published a draft notice of availability requesting public comment on 
the information collection provisions. Nineteen comments were received 
of which 4 remarked on the information collection.
    (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 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,

[[Page 63160]]

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) 
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 of 
this document are underestimated if the estimate accounts for the time 
required to become familiar with the 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 
e-mail address are provided by us for the purpose of minimizing the 
need to learn the SPL standard before submitting information 
    (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.

                                 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
 including new
 labeler code
Annual updates of              3,256               2.99              9,735                  2             19,470
New drug listings              1,567               6.57             10,295                  2             20,590
New listings for                 146              10.06              1,469                  2              2,938
 private label
June and December              1,677              11.21             18,799                  2             37,598
 updates of all
 drug listing
Waiver requests                    1                  1                  1                  1                  1
Total                                                                                                     81,745
\1\ There are no capital costs or operating and maintenance costs associated with this collection of

                               Table 2.--Estimated Annual Recordkeeping Burden\1\
                         No. of        Annual Frequency     Total Annual
     Activity        Recordkeepers    per Recordkeeping       Records       Hours per  Record     Total Hours
One-time                       3,295                  1              3,295                 40            131,800
 preparation of
SOP maintenance                3,295                  1              3,295                  1              3,295

[[Page 63161]]

Total                                                                                                    135,095
\1\ There are no capital costs or operating and maintenance costs associated with this collection of

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 
    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 
    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, terminology, 
and data standards regarding SPL files.\4\

    \3\ See http://www.fda.gov/oc/datacouncil/xforms.html.
    \4\ 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 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 

    Dated: October 15, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-25338 Filed 10-22-08; 8:45 am]