[Federal Register Volume 67, Number 86 (Friday, May 3, 2002)]
[Proposed Rules]
[Pages 22367-22375]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-11039]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 314 and 601

[Docket No. 00N-1652]
RIN 0910-AB91


Requirements for Submission of Labeling for Human Prescription 
Drugs and Biologics in Electronic Format

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to amend 
its regulations governing the format in which certain labeling is 
required to be submitted for review with new drug applications (NDAs), 
certain biological license applications (BLAs), abbreviated new drug 
applications (ANDAs), supplements, and annual reports. The proposal 
would require that certain labeling content be submitted electronically 
in a form that FDA can process, review, and archive. Submitting the 
content of labeling in electronic format would simplify the drug 
labeling review process and speed up the approval of labeling changes.

DATES: Submit written or electronic comments by August 1, 2002. Submit 
written comments on the information collection requirements by June 3, 
2002. See section X of this document for the proposed effective date of 
a final rule based on this document.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments. Submit written comments on the information 
collection provisions to the Office of Information and Regulatory 
Affairs, Office of Management and Budget (OMB), New Executive Office 
Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn: Stuart 
Shapiro, Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT:
    Randy Levin, Center for Drug Evaluation and Research (HFD-1), Food 
and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-
594-5411, or
    Robert A. Yetter, Center for Biologics Evaluation and Research 
(HFM-10), Food and Drug Administration, 1401 Rockville Pike, Rockville, 
MD 20852, 301-827-0373.

SUPPLEMENTARY INFORMATION:

I. Background

A. Current Labeling Submission Requirements

    Section Sec. 314.50 (21 CFR 314.50) of our (FDA's) current 
regulations describes the content and format requirements for NDAs. 
Under Sec. 314.50(e)(2)(ii), an applicant is required to submit, in the 
archival copy of an application, copies of the label and all labeling 
for the drug product. Under Sec. 314.50(l)(1), information in the 
archival copy required under Sec. 314.50(a) (i.e., the application 
form, including the signature of the applicant) and Sec. 314.50(e) 
(i.e., samples and labeling) must be submitted to the agency on paper, 
while other required information may be submitted either on paper or on 
microfiche (or another suitable microform system, if FDA and the 
applicant agree). Under Sec. 314.71(b) (21 CFR 314.71(b)), supplements 
to approved applications submitted to the agency under Sec. 314.70 (21 
CFR 314.70) must follow the procedures described in Sec. 314.50. In 
addition, Sec. 314.81(b)(2)(iii) (21 CFR 314.81(b)(2)(iii)) requires 
that ``currently used professional labeling, patient brochures, or 
package inserts'' be submitted with annual reports.
    Section Sec. 314.94 (21 CFR 314.94) sets forth requirements for the 
content and format of ANDAs. Under Sec. 314.94(a)(8)(ii), the archival 
copy of an ANDA must include copies of the label and all labeling for 
the drug product. Under Sec. 314.94(d), an applicant may submit all or 
portions of the archival copy of an ANDA in any form that FDA and the 
applicant agree is acceptable. Under Sec. 314.97 (21 CFR 314.97), 
supplements and other changes to approved ANDAs must be submitted to 
the agency under the requirements of Secs. 314.70 and 314.71. As noted 
previously, under Sec. 314.71(b), supplements to approved applications 
submitted to the agency under 314.70 must follow the procedures 
described in Sec. 314.50. Finally, under Sec. 314.98(c) (21 CFR 
314.98(c)), ANDA applicants must submit annual reports as required in 
Sec. 314.81(b)(2)(iii).
    Section Sec. 601.2 (21 CFR 601.2) describes the requirements for 
submission of a BLA, which include the

[[Page 22368]]

requirement that specimens of enclosures and Medication Guides for a 
product, if any, be submitted. Section 601.12 (21 CFR 601.12) describes 
the requirements to make changes to an approved BLA, including labeling 
changes. Under Sec. 601.12(f), labeling changes to a biological product 
approved under a BLA may generally only be made after the approval of a 
labeling supplement to the BLA, although certain types of labeling 
changes may be made before FDA approval of a supplement or by reporting 
the change in an annual report. Neither Sec. 601.2 nor Sec. 601.12 
specifies a format in which the labeling or other information required 
in BLAs, BLA supplements, or annual reports must be submitted to FDA.
    The term ``labeling'' used in Secs. 314.50, 314.94, 314.81, and 
601.12 is defined in section 201(m) of the Federal Food, Drug, and 
Cosmetic Act (the act) (21 U.S.C. 321(m)) to mean both labels\1\ and 
other written, printed, or graphic matter upon any article or any of 
its containers or wrappers, or accompanying such article. Thus, 
requiring the submission of ``labeling'' entails submission of the 
label (i.e., the label on the immediate container) and labeling. 
Labeling consists of the comprehensive prescription drug labeling 
directed to health care practitioners (i.e., the labeling required 
under Sec. 201.100(d)(3) (21 CFR 201.100(d)(3)), commonly referred to 
as the ``package insert'' or ``professional labeling'') and other 
labeling.\2\
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    \1\Under section 201(k) of the act, the term ``label'' means a 
display of written, printed, or graphic matter upon the immediate 
container of any article.
    \2\Section 201.100(d) requires that any labeling distributed by 
or on behalf of the manufacturer, packer, or distributor of the 
drug, that furnishes or purports to furnish information for use of 
the drug, or which prescribes, recommends, or suggests a dosage for 
the use of the drug, must meet the content and format requirements 
in 21 CFR 201.56 and 201.57.
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B. The Effect of the Proposed Rule on Current Submission Requirements

    Under this proposal, applicants would be required to submit to us 
in electronic format the content of the package insert or professional 
labeling, including all text, tables, and figures. As explained below, 
this submission should be formatted in the manner described in agency 
guidance on electronic submissions.
    This proposed requirement would be in addition to existing 
requirements, described in section I.A of this document, that copies of 
the label and labeling and specimens of enclosures be submitted. For 
example, copies of the package insert must still be submitted to us in 
an NDA under Sec. 314.50(e)(2)(ii). Copies submitted to us must be 
identical to the label and labeling and specimens of enclosures that 
appear in the package insert, on the immediate container, or in any 
other form distributed. Under this proposal, these copies may be 
submitted electronically or on paper.

C. Electronic Format Submission Initiatives

    In the Federal Register of March 20, 1997 (62 FR 13430), we 
published a regulation on electronic records and electronic signatures 
(part 11 (21 CFR part 11)). Part 11 generally provides that in 
instances where records are required to be submitted to the agency, 
such records may be submitted in electronic format instead of paper 
format, provided the controls in part 11 are met and we have identified 
the submission in the public docket as the type of submission we are 
prepared to accept in electronic format.
    Although we have not up to this time required regulatory 
submissions in electronic format, we have issued guidances describing 
how to submit NDAs, BLAs, and other types of regulatory submissions in 
electronic format. In the Federal Register of January 28, 1999 (64 FR 
4432), we announced the availability of a guidance entitled ``Providing 
Regulatory Submissions in Electronic Format--NDA's'' (the NDA 
electronic submission guidance), which provided information on how to 
submit a complete archival copy of an NDA in electronic format. The 
guidance applies to the submission of original NDAs, as well as to the 
submission of supplements and amendments to NDAs. Among other things, 
the NDA electronic submission guidance provides recommendations on how 
to submit ``labeling text'' in electronic format. ``Labeling text'' is 
the term used in the NDA electronic submission guidance to mean 
labeling required under Sec. 201.100(d)(3), including all text, tables, 
and figures required by or included under authority of those sections. 
The term ``content of labeling,'' as used in this rulemaking, is 
intended to mean the same as the term ``labeling text,'' as used in the 
guidance. The NDA electronic submission guidance recommends that 
labeling text be submitted as a portable document format (PDF) file and 
that the file be submitted in the following format:
     The print area (i.e., the area of the PDF file when 
printed) should fit on an 8 1/2- by 11-inch sheet of paper with 1-inch 
margins;
     The page orientation should be portrait;
     The file should not contain any columns, headers, or 
footers; and
     The files should be paginated, beginning with page 1. The 
guidance also describes recommended font types and minimum font sizes 
for the PDF file text.
    In November 1999, we published a guidance to assist applicants in 
submitting documents in electronic format for review and archive 
purposes as part of a BLA, product license application (PLA), or 
establishment license application (ELA) (64 FR 61647, November 12, 
1999).
    In January 1999, we issued a guidance on general considerations for 
electronic submissions entitled ``Providing Regulatory Submissions in 
Electronic Format--General Considerations'' (the general considerations 
guidance) (64 FR 4433, January 28, 1999). In the general considerations 
guidance, we include a description of the types of electronic file 
formats that we are able to accept to process, review, and archive 
electronic documents. The general considerations guidance states that 
documents submitted in electronic format should enable the user to: (1) 
Easily view a clear and legible copy of the information; (2) print each 
document page by page while maintaining fonts, special orientations, 
table formats, and page numbers; and (3) copy text and images 
electronically into common word processing documents. To achieve these 
and other goals, we recommend that all electronic documents be 
submitted as PDF files.

II. Rationale for Requiring Electronic Submission of the Content of 
Labeling

    As discussed in section I of this document, until now, the 
initiatives we have undertaken have been focused on permitting, but not 
requiring, applicants to submit required regulatory documents in 
electronic format. For a number of reasons, we believe that it is 
important to require that the content of labeling (i.e., the labeling 
required under Sec. 201.100(d)(3), including all text, tables, and 
figures) be submitted to us electronically for prescription drugs and 
biological products that are subject to the requirements of 
Sec. 201.100(d)(3).

A. Why Is It Important for the Content of Labeling To Be Submitted 
Electronically?

    Each year, we receive more than 1,000 proposed labeling changes for 
approved NDAs and BLAs, and more than 2,600 proposed original and 
supplemental labeling changes for ANDAs. As part of the review process, 
we conduct a word-for-word comparison of the proposed labeling with the 
last approved labeling

[[Page 22369]]

to verify that all labeling changes have been identified. In addition, 
for ANDAs, we conduct a word-for-word comparison of the labeling for 
the proposed generic drug product and the reference listed drug to 
verify that any differences in labeling have been correctly annotated 
and explained by the ANDA applicant under Sec. 314.94(a)(8)(iii). 
Currently, a reviewer must conduct these comparisons manually using two 
paper copies of the labeling. This manual comparison is slow and 
subject to error.
    The proposed rule would require that the content of labeling be 
submitted in an electronic file in a form that we can process, review, 
and archive. The formatting of these submissions will allow electronic 
review and comparison of labeling files. We believe that the use of 
computer technology to identify changes in different versions of the 
labeling would greatly enhance the accuracy and speed of this part of 
the review. The ability to quickly identify changes in different 
versions of the labeling would shorten the time needed to approve 
labeling changes and reduce the amount of resources we need to devote 
to labeling review. Our ability to protect the public health will be 
enhanced because electronic review and comparison of labeling files 
will provide a higher degree of certainty that all portions of 
prescription drug labeling are appropriate. Furthermore, in certain 
circumstances (e.g., changes to NDA labeling made under 
Sec. 314.70(c)), we review labeling changes after they have been 
implemented. We may find the revised labeling to be inappropriate. Our 
ability to quickly identify the changes and correct the labeling would 
minimize public exposure to the inappropriate labeling.

B. Why Should the Content of Labeling Be Submitted in PDF?

    For the agency to efficiently use computer technology to identify 
changes between different versions of labeling, we need to receive 
labeling in an electronic file format that supports word-for-word 
comparisons of files and in a form we can process, review, and archive. 
Although there are several file formats and computer software 
applications capable of providing the functions necessary for review 
purposes, it would not be cost effective to purchase many different 
types or versions of software and train our employees to use them, or 
to archive many different file formats. At this time, PDF is the only 
type of electronic file format that we have the ability to use to 
process, review, and archive submissions.
    We believe that of the file formats and software applications 
currently available, PDF best meets our needs while keeping costs to 
applicants low. Using commercially available software, an electronic 
source document created by any number of programs (e.g., word 
processors, spreadsheets, desktop publishing programs) can be converted 
to a PDF file, preserving the fonts, formatting, colors, and graphics 
of the source document, regardless of the application and platform used 
to create it. The PDF file can be copied onto a floppy disk or CD-ROM 
and shared with other users who may use PDF reading software to view, 
navigate through, and print the document exactly as it appears in its 
original form. Once we receive a PDF document, we can use our current 
software to compare the text of the file received with other PDF files 
and view, search, annotate, and print the file. Available software also 
allows us to copy text, tables, and figures from the file. Software to 
convert electronic files to PDF format is commercially available at a 
cost of approximately $100 to $300. Additionally, the technology 
necessary to create PDF documents is publicly available, and applicants 
that choose to do so may use their own software to create PDF documents 
for submission.
    Although we believe that PDF is currently the best file format in 
which to submit labeling electronically, future advancements in 
computer technology and computer software design may result in new 
types of file formats and software to better meet our needs and those 
of industry. Therefore, we believe it is important to evaluate these 
new technologies as they become available. If we determine that a new 
technology provides important benefits over PDF, we need the 
flexibility to identify new or additional formats for electronic 
labeling submissions. For this reason, we are not proposing to require 
specifically that PDF be used to submit labeling content 
electronically. Rather, we are proposing that the content of labeling 
be submitted in a form that we can process, review, and archive. This 
language will provide us the flexibility to recommend file formats or 
software other than PDF in future guidance, to make electronic 
submissions easier.

C. Why Does the Agency Make Specific Recommendations for Electronic 
Labeling Submissions?

    After the agency receives the labeling, we compare it to the last-
submitted labeling and look for differences in text, figures, and other 
changes. In the process of review, we frequently copy, paste, and print 
portions of the labeling. These functions are most easily performed 
using PDF when: (1) There are no headers or footers (other than page 
numbers) to compare or copy; (2) there are no columns to interfere with 
the copy and paste function or with navigation through the labeling; 
(3) the font size is sufficiently large to be easily read; (4) the page 
orientation is portrait; (5) the pagination starts with page one to 
avoid confusion when referring to changes; and (6) the page size is not 
too large to be printed on a standard page and not too small to print 
efficiently. Therefore, electronic files submitted to us should be 
prepared, organized, and sent to us in accordance with the 
recommendations in the most recent agency guidance so that they may be 
easily reviewed and used. Submitting documents according to these 
recommendations will ensure a uniformity of submissions that will 
improve the efficiency and speed of agency reviews.

III. Description of the Proposed Rule

    The proposal would revise our regulations to require electronic 
submission of the content of labeling for NDAs, certain BLAs, ANDAs, 
supplements, and annual reports. This requirement would be in addition 
to existing requirements, found elsewhere in our regulations, that 
copies of labeling be submitted. The proposal would also make minor 
changes to reformat and modernize certain regulatory provisions.

A. Electronic Submission of the Content of Labeling

    Under the proposal, Secs. 314.50(l), 314.81(b)(2)(iii), and 
314.94(d)(1) would be revised to require applicants to submit the 
content of labeling in NDAs, ANDAs, supplements, and annual reports 
electronically in a form that we can process, review, and archive. 
Under proposed Sec. 314.94(d)(1), ANDA applicants would be required to 
submit in electronic format the content of labeling for the proposed 
drug product (i.e., the content of the generic drug product labeling). 
ANDA applicants would not be required to submit in electronic format 
the content of labeling for the reference listed drug product. Under 
proposed Sec. 601.14, applicants for biological products subject to the 
requirements of Sec. 201.100(d)(3) would be required to submit the 
content of labeling in BLAs, supplements, and annual reports 
electronically in a form that we can process, review, and archive.
    As discussed in section II of this document, the only type of 
electronic file format that we have the ability to

[[Page 22370]]

accept for processing, review, and archiving at this time is PDF, and 
the economic impact estimates in section IX of this document have been 
developed based on the assumption that PDF would be used. As new file 
formats and software applications are developed, we may recommend that 
different or additional types of file formats (i.e., other than PDF) 
should be used to submit labeling electronically. The language of the 
proposed rule (i.e., that the content of labeling must be submitted in 
a form that we can process, review, and archive) will provide us the 
flexibility to recommend file formats or software other than PDF in 
future guidance, if appropriate. If we later recommend other file 
formats or software, we intend to provide advance notice, in accordance 
with FDA's good guidance practice regulations under Sec. 10.115 of this 
chapter, so that affected parties will have adequate time to convert to 
the new format or software. We will also identify any format or 
software changes in public docket number 92S-0251.\3\ During the 
transition time, we intend to accept submissions using either file 
format or software.
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    \3\This docket can be accessed on the Internet at http://www.fda.gov/ohrms/dockets/dockets/92s0251/92s0251.htm.
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B. Electronic and Paper Submission of Archival Copy of an NDA

    Under current Sec. 314.50(l)(1), applicants must submit the 
application form required under Sec. 314.50(a) and samples and labeling 
information required under Sec. 314.50(e) on paper, while other 
information required in the archival copy of an NDA (i.e., the 
information required under Sec. 314.50(b), (c), (d), and (f)) may be 
submitted on microfiche or another suitable microform system. The 
proposal would revise Sec. 314.50 (1)(1) to require applicants to 
submit the content of labeling electronically (i.e., in a computer 
file). (See section III.C of this document for proposal to delete 
specific references to microfiche or other suitable microform systems.)
    Other portions of the archival copy of an NDA would be submitted to 
the agency either on paper or in electronic format provided that 
electronic submissions are made in accordance with part 11 of this 
chapter. Currently, under Sec. 11.2(b)(2), FDA is able to accept all 
portions of the archival copy of the NDA electronically, except for 
documents requiring signatures. The agency is in the process of 
developing the ability to accept signatures electronically and plans to 
have this capability in the future. At that time, electronic signatures 
must comply with the requirements in part 11 pertaining to electronic 
signatures.

C. Deletion of References to Specific Media

    The proposal would revise Secs. 314.50(l)(1) and 314.94(d)(1) so 
that they no longer refer to means of submission through specific, 
nonpaper media. Section 314.50(l)(1) allows an NDA applicant to submit 
on microfiche the portions of the archival copy of an application 
described in Sec. 314.50(b) through (d). If we agree, tabulations of 
patient data and case report forms described in Sec. 314.50(f) may also 
be submitted on microfiche. If we agree, the applicant may use another 
suitable microform system. Section 314.94(d)(1) allows an ANDA 
applicant to submit an archival copy of the ANDA in any form, including 
microfiche, optical disc, and magnetic tape, if we find it acceptable.
    We are proposing to delete the specific references to microfiche, 
microform, optical disc, and magnetic tape in Secs. 314.50(l)(1) and 
314.94(d)(1). We believe we can more readily respond to technological 
advances and our increasing knowledge of and experience with certain 
types of media by establishing regulations that set out general 
requirements for the use of media (i.e., on paper and in electronic 
format) and by using guidance documents to provide our current thinking 
on the specific types of media that we are able to process, review, and 
archive. We believe that this approach will allow us to be more 
responsive to the changing technological environment.

D. Formatting Changes

    The proposal would amend Sec. 314.50(l) by adding section headings 
to paragraphs (l)(1) through (l)(4) and by replacing the word ``shall'' 
with the word ``must.'' We anticipate that these minor changes will 
clarify the regulation and make it easier to read.

IV. Part 11 Requirements for Electronic Submissions

    Our part 11 regulations, among other things, set forth the criteria 
under which records required to be submitted to us may be submitted in 
electronic format in lieu of paper. Section 11.2(b) states that, for 
records submitted to the agency, persons may use electronic records in 
lieu of paper records, in whole or part, provided the requirements of 
part 11 are met and the documents or parts of documents to be submitted 
have been identified by the agency in public docket No. 92S-0251\4\ as 
being the type of submission the agency is prepared to accept in 
electronic format.
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    \4\This docket can be accessed on the Internet at http://www.fda.gov/ohrms/dockets/dockets/92s0251/92s0251.htm.
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    Part 11 permits the widest possible use of electronic technology, 
compatible with our responsibility to promote and protect the public 
health (62 FR 13430). Specifically, part 11 helps to ensure the 
integrity, authenticity, and when appropriate, the confidentiality of 
electronic records and helps to safeguard against the possible 
repudiation of those records. The controls in subpart B of part 11 are 
intended to further this purpose. However, with respect to the 
submission of labeling content in electronic format, the agency 
believes that several of the subpart B requirements are not necessary 
to further the goals of part 11. For example, validation for the system 
used to generate the labeling record under this proposal is not 
necessary. For the purposes of this rule, the applicant's verification 
that the information in the labeling record is accurate serves the same 
objective. The applicant also certifies on Form FDA 356h that the 
record is accurate. Because our review is based on the version of the 
labeling record submitted to us and earlier versions of the record or 
changes made to the earlier versions are not relevant to our analysis, 
other controls related to the creation, modification, and maintenance 
of the labeling records are also not needed. Therefore, we propose to 
exempt the submission of labeling content under this proposed rule from 
the requirements of Sec. 11.10(a), (c) through (h), and (k) and the 
corresponding requirements imposed by Sec. 11.30.
    Labeling submitted in conjunction with NDAs, BLAs, and supplements 
to those applications has previously been identified by the agency in 
public docket No. 92S-0251 as being acceptable for submission in 
electronic format. Should this proposal be finalized, those portions of 
annual reports, ANDAs, and ANDA supplements to which the final rule is 
applicable will also be identified in the public docket as acceptable 
for submission in electronic format.
    As discussed above, we found that some of the controls described in 
part 11 are not necessary to ensure the integrity and authenticity of 
labeling content submissions. Accordingly, we are reevaluating the 
necessity of some of the controls in part 11 as they apply to

[[Page 22371]]

different submissions, including records voluntarily submitted in 
electronic format. We may consider whether to propose amendments to the 
part 11 regulations as a result of our reevaluation. Sponsors should 
contact us with questions concerning the applicability of subpart B 
controls to records voluntarily submitted in electronic format.

V. Legal Authority

    Our legal authority to amend our regulations governing the format 
of labeling for human prescription drugs and biologics derives from 
sections 201, 301, 501, 502, 503, 505, 506, 506A, 506B, 506C, 510, 513-
516, 518-520, 701, 704, 721, and 801 of the act (21 U.S.C. 321, 331, 
351, 352, 353, 355, 356, 356a, 356b, 356c, 360, 360c-360f, 360h-360j, 
371, 374, 379e, and 381); 15 U.S.C. 1451-1561; the Public Health 
Service Act (42 U.S.C. 216, 241, 262, 263, 264); and sec. 122, Public 
L. 105-115, 111 Stat. 2322 (21 U.S.C. 355 note).

VI. Paperwork Reduction Act of 1995

    This proposed rule contains collections of information requirements 
that are subject to review by OMB under the Paperwork Reduction Act of 
1995 (44 U.S.C. 3501-3520). A description of these requirements are 
given below with an estimate of the annual reporting burden. Included 
in the estimate is the time for reviewing instructions, searching 
existing data sources, gathering and maintaining the date needed, and 
completing and reviewing each collection of information.
    We invite comments on: (1) Whether the proposed collection of 
information is necessary for proper performance of our functions, 
including whether the information will have practical utility; (2) the 
accuracy of our 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 of information on respondents, including through the use of 
automated collection techniques, when appropriate, and other forms of 
information technology.
    Title: Requirements for Submission of Labeling for Human 
Prescription Drugs and Biologics in Electronic Format
    Description: We are proposing to require that certain labeling 
content be submitted to us for review in electronic form. The proposal 
would require that the content of labeling for prescription drug and 
biological products that is required under Sec. 201.100(d)(3) be 
submitted to us in electronic format. This labeling is submitted to us 
with NDAs, BLAs, ANDAs, supplements, and annual reports. We are 
proposing to require that the content of this labeling be submitted in 
electronic format because the use of computer technology to identify 
changes in different versions of the labeling would greatly enhance the 
accuracy and speed of our review of product labeling. The ability to 
quickly identify changes in labeling text would also shorten the time 
needed to approve labeling changes.
    As discussed in section I of this document, copies of product 
labeling are currently required to be submitted to us for review in 
NDAs, certain BLAs, ANDAs, certain supplements, and annual reports 
under Secs. 314.50, 314.70, 314.81, 314.94, 314.97, 314.98, 601.2, and 
601.12. Under this proposed rule, copies of labeling may be submitted 
electronically or on paper. The proposal would require that the content 
of the labeling required under Sec. 201.100(d)(3) be submitted in 
electronic format.
    The proposal would amend current Secs. 314.50(l), 
314.81(b)(2)(iii), 314.94(d)(1), and part 601 to require that the 
content of labeling (i.e., labeling required under Sec. 201.100(d)(3), 
including all text, tables, and figures) be submitted to us 
electronically in a form that we can process, review, and archive. 
Under Sec. 314.71, supplements to NDAs and ANDAs submitted to us under 
Secs. 314.70 and 314.97 must follow the procedures of Sec. 314.50. In 
addition, ANDA annual reports submitted to us under Sec. 314.98 must 
follow the requirements of Sec. 314.81. Under proposed Sec. 601.14, the 
content of labeling submitted with BLAs under Sec. 601.2, supplements 
to BLAs under Sec. 601.12, and BLA annual reports under Sec. 601.12 for 
products subject to the requirements of Sec. 201.100(d)(3) must be in 
electronic format. Therefore, if labeling is required as part of an 
NDA, ANDA, or BLA, an NDA, ANDA, or BLA supplement, or an NDA, ANDA, or 
BLA annual report, the content of labeling must be submitted to us 
electronically in a form that we can process, review, and archive. As 
discussed in section II of this document, these electronic files should 
be provided to us in accordance with the recommendations in agency 
guidance.
    Description of Respondents: An applicant submitting an NDA, ANDA, 
BLA, supplement, or annual report to us for a drug or biological 
product.
    Burden Estimate: Table 1 of this document provides an estimate of 
the annual reporting burden under the proposed rule.
    This rule would require applicants to submit in an electronic form 
that we can process, review, and archive, the content of labeling with 
NDAs, BLAs, ANDAs, annual reports, and certain supplements.\5\ 
Currently, applicants are not required to submit this labeling 
electronically. Because we do not know the number of applicants that 
currently have the capability to submit electronic files and do not 
have firsthand information on how labeling files are currently 
maintained, the following estimates are based on our experience with 
voluntary electronic submissions and with converting word processing 
files to PDF format. Therefore, we request that interested parties 
submit comments on the accuracy of these estimates.
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    \5\As discussed in section II of this document, PDF is the only 
type of electronic file format that we have the ability to accept 
for processing, reviewing, and archiving at this time. Therefore, 
the estimates in this section are based on submission of files in 
PDF format.
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    The reporting burdens for submitting labeling as currently required 
under Secs. 314.50, 314.70, 314.81, 314.94, 314.97, and 314.98 have 
previously been estimated by us, and this collection of information was 
approved by OMB until March 31, 2002, under OMB control number 0910-
0001. The reporting burdens associated with current Secs. 601.2 and 
601.12 have also previously been estimated, and this collection of 
information was approved by OMB until March 31, 2003, under OMB control 
number 0910-0338, and until August 31, 2003, under OMB control number 
0910-0315, respectively. We are not reestimating these approved burdens 
in this rulemaking. Only the additional reporting burdens associated 
with the electronic submission of the content of labeling are 
estimated.
    New NDAs (Sec. 314.50), ANDAs (Sec. 314.94), and BLAs (Sec. 601.2): 
Based on data in the approved collections of information for 
Secs. 314.50, 314.94, and 601.2, we estimate that approximately 83 NDA 
applicants, 117 ANDA applicants, and 17 BLA applicants (respondents) 
submit applications to us annually. We estimate that the total annual 
responses, i.e., the total number of NDAs, ANDAs, and BLAs submitted to 
us per year, will remain approximately 124 NDAs, 464 ANDAs, and 63 
BLAs. Based on our experience with voluntary electronic submissions and 
our knowledge of the drug and biologic industries, we assume that 
applicants for new NDAs, ANDAs, and BLAs will already have the 
necessary labeling in an electronic format that can be easily accessed 
and converted to a PDF file. Thus, we have estimated that the hours per 
response, i.e., the

[[Page 22372]]

additional time necessary for submission of the content of labeling in 
electronic format for these applications, will be less than 15 minutes. 
Therefore, we estimate that respondents will spend approximately 163 
hours per year submitting the content of labeling to us in accordance 
with the proposed rule.
    Supplements to NDAs (Sec. 314.70) and ANDAs (Sec. 314.97) and BLAs 
(Sec. 601.12(f)(1) and (f)(2)): Based on data in the approved 
collections of information for Secs. 314.70, 314.97, and 601.12(f)(1) 
and (f)(2), we estimate that approximately 418 NDA applicants, 152 ANDA 
applicants, and 22 BLA applicants (respondents) submit supplements to 
approved applications to us annually. We estimate that the total annual 
responses, i.e., the total number of NDA, ANDA, and BLA supplements 
submitted to us per year, will remain approximately 2,229 NDA 
supplements, 3,000 ANDA supplements, and 22 BLA supplements. Based on 
our experience reviewing supplements to applications and because not 
all NDA and ANDA supplements are required to include labeling, we 
estimate that, under the proposed rule, approximately 45 percent of NDA 
supplements (i.e., 1,003 NDA supplements) and 20 percent of ANDA 
supplements (i.e., 600 ANDA supplements) would be required to include 
the content of labeling in electronic form. Under the proposed rule, 
all 22 BLA labeling supplements would be required to include the 
content of labeling in electronic form. Based on our experience with 
voluntary electronic submissions and our knowledge of the drug and 
biologic industries, we assume that applicants submitting supplements 
to NDAs, ANDAs, and BLAs will already have the necessary labeling in an 
electronic format that can be easily accessed and converted to a PDF 
file. Thus, we have estimated that the hours per response, i.e., the 
additional time necessary for submission of the content of labeling in 
electronic format for these supplements, will be less than 15 minutes. 
Therefore, we estimate that respondents would spend approximately 406 
hours per year submitting the content of labeling to us in supplements 
under the proposed rule.
    Annual Reports for NDAs (Sec. 314.81), ANDAs (Sec. 314.98), and 
BLAs (Sec. 601.12(f)(3)): Based on data in the approved collections of 
information for Secs. 314.81, 314.98, and 601.12(f)(3), we estimate 
that approximately 269 NDA applicants, 265 ANDA applicants, and 70 BLA 
applicants (respondents) submit annual reports to us annually. We also 
estimate that each NDA applicant submits to us approximately 9.06 
annual reports, each ANDA applicant submits approximately 17.17 annual 
reports, and each BLA applicant submits approximately 1.42 annual 
reports each year. Further, we estimate that the total annual 
responses, i.e., the total number of annual reports submitted to us per 
year, will remain approximately 2,438 NDA annual reports, 4,551 ANDA 
annual reports, and 100 BLA annual reports.
    Based on our experience with voluntary electronic submissions and 
our knowledge of the drug and biologic industries, we estimate that 
approximately 80 percent of NDA annual reports (1,950 NDA annual 
reports), 70 percent of ANDA annual reports (3,186 ANDA annual 
reports), and 80 percent of BLA annual reports (80 BLA annual reports), 
will already have the necessary labeling in an electronic format that 
can be easily accessed and converted to a PDF file. As discussed above, 
we estimate that each NDA applicant submits to us approximately 9.06 
annual reports, each ANDA applicant submits approximately 17.17 annual 
reports, and each BLA applicant submits approximately 1.42 annual 
reports each year. Therefore, approximately 215 NDA applicants, 186 
ANDA applicants, and 56 BLA applicants can easily access labeling in 
electronic form and convert it to a PDF file. For the applicants 
submitting these annual reports, we estimate that the hours per 
response, i.e., the additional time necessary for submission of the 
content of labeling in electronic format in the annual report, will be 
less than 15 minutes.
    We recognize that annual reports for some drug and biological 
products, particularly older products for which labeling changes have 
not been made in several years, may require additional steps. To 
include labeling content in electronic format, we estimate that 
approximately 20 percent of NDA annual reports (488 NDA annual 
reports), 30 percent of ANDA annual reports (1,365 ANDA annual 
reports), and 20 percent of BLA annual reports (20 BLA annual reports) 
will be submitted by applicants who may need to access the labeling in 
their archives and put the content of labeling into an electronic 
format and convert it to a PDF file. As discussed above, we estimate 
that each NDA applicant submits to us approximately 9.06 annual 
reports, each ANDA applicant submits approximately 17.17 annual 
reports, and each BLA applicant submits approximately 1.42 annual 
reports each year. Therefore, under the proposed rule, approximately 54 
NDA applicants, 79 ANDA applicants, and 14 BLA applicants would need to 
put labeling content in an electronic format and convert it to a PDF 
file. We estimate that the hours per response, i.e., the time it will 
take an applicant to submit the labeling content electronically for 
these annual reports, will be approximately 8 hours.
    Therefore, we estimate that in the first year, respondents will 
spend approximately 16,289 hours submitting the content of labeling to 
us in annual reports under the proposed rule. This expenditure of time 
will only be necessary the first time that an annual report is 
submitted with the content of labeling in electronic format. Once the 
content of labeling has been converted to an electronic format, the 
time necessary to submit the content of labeling in subsequent annual 
reports will be the same as that for the other types of submissions, or 
less than 15 minutes. Therefore, we estimate that, in subsequent years, 
respondents will spend approximately 1,773 hours per year submitting 
the content of labeling in annual reports.

                                                     Table 1.--Estimated Annual Reporting Burden\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                    No. of
                                 21 CFR Section                                      No. of      Responses per  Total Annual    Hours per    Total Hours
                                                                                   Respondents    Respondent      Responses     Response
--------------------------------------------------------------------------------------------------------------------------------------------------------
Applications:
3.14.50                                                                                83              1.49         124             .25           31
314.94                                                                                117              3.96         464             .25          116
601.14 (Applications submitted under Sec.  601.2)                                      17              3.71          63             .25           16
Subtotal, applications                                                                                                                           163
Supplements:
314.70                                                                                418              2.39       1,003             .25          251

[[Page 22373]]

 
314.97                                                                                152              3.94         600             .25          150
601.14 (Supplements submitted under Sec.  601.12(f)(1) and (f)(2))                     22              1.0           22             .25            6
Subtotal, supplements                                                                                                                            407
Annual Reports:
314.81 (Products not requiring additional steps for electronic submission)            215              9.06       1,950             .25          488
314.81 (Products requiring additional steps for electronic submission)                 54              9.06         488            8           3,904
314.98 (Products not requiring additional steps for electronic submission)            186             17.17       3,186             .25          797
314.98 (Products requiring additional steps for electronic submission)                 79             17.17       1,365            8          10,920
601.14 (Annual reports submitted under Sec.  601.12(f)(3) not requiring                56              1.4           80             .25           20
 additional steps for electronic submission)
601.14 (Annual reports submitted under Sec.  601.12(f)(3) requiring additional         14              1.4           20            8             160
 steps for electronic submission)
Subtotal, annual reports, year one                                                                                                            16,289
Subtotal, annual reports, subsequent years\2\                                                                                                  1,773
  Total, year one                                                                                                                             16,859
  Total, subsequent years\2\                                                                                                                   2,343
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are one-time capital costs to: (1) Acquire computer software; (2) train employees to use the software; and (3) convert certain labeling to an
  electronic format. These costs are estimated to be about $934,650 (see section IX of this document). There are no operating or maintenance costs
  associated with this collection of information.
\2\ We estimate that for certain annual reports, respondents will spend 8 hours per response in the first year. We estimate that in subsequent years
  respondents will spend less than 15 minutes per response for all annual reports.

    In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C. 
3507(d)), we have submitted the information collection requirements of 
this proposed rule to OMB for review. Interested persons are requested 
to send comments regarding information collection by June 3, 2002, to 
the Office of Information and Regulatory Affairs, OMB, New Executive 
Office Bldg., 725 17th St. NW., rm. 10235, Washington DC 20503, Attn: 
Stuart Shapiro, Desk Officer for FDA.

VII. Environmental Impact

    We have determined under 21 CFR 25.30(h) that this action is of a 
type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

VIII. Federalism

    We have analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13132. We have determined that 
the proposed rule does not contain policies that have substantial 
direct effects on the States, on the relationship between the National 
Government and the States, or on the distribution of power and 
responsibilities among the various levels of government. Accordingly, 
we have concluded that the proposed rule does not contain policies that 
have federalism implications as defined in the order and, consequently, 
a federalism summary impact statement is not required.

IX. Analysis of Economic Impacts

    We have examined the impacts of the proposed rule under Executive 
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612 (as 
amended by subtitle D of the Small Business Regulatory Fairness Act of 
1996 (Public Law 104-121))), and the Unfunded Mandates Reform Act of 
1995 (Public Law 104-4). Executive Order 12866 directs agencies to 
assess all costs and benefits of available regulatory alternatives and, 
when regulation is necessary, to select regulatory approaches that 
maximize net benefits (including potential economic, environmental, 
public health and safety, and other advantages; distributive impacts; 
and equity). Under the Regulatory Flexibility Act, if a rule may have a 
significant economic impact on a substantial number of small entities, 
an agency must consider alternatives that would minimize the economic 
impact of the rule on small entities. Section 202(a) of the Unfunded 
Mandates Reform Act of 1995 requires that agencies prepare a written 
assessment of anticipated costs and benefits before proposing any rule 
that may result in an expenditure by State, local, and tribal 
governments, in the aggregate, or by the private sector, of $100 
million in any one year (adjusted annually for inflation).
    We believe that this proposed rule is consistent with the 
regulatory philosophy and principles identified in Executive Order 
12866 and in these two statutes. The proposed rule is a significant 
regulatory action as defined in section 3 paragraph (f)(4) of the 
Executive order. However, as shown below, the proposed rule will not be 
an economically significant regulatory action as defined by the 
Executive order and will not require further analysis under the 
Regulatory Flexibility Act.
    The Unfunded Mandates Reform Act of 1995 does not require FDA to 
prepare a statement of costs and benefits for the proposed rule because 
the proposed rule would not result in an expenditure of $100 million in 
any one year, adjusted for inflation. The current inflation-adjusted 
statutory threshold is approximately $110 million.
    The purpose of this proposal is to require applicants to submit in 
electronic format the content of labeling required under 
Sec. 201.100(d)(3) in NDAs, ANDAs, BLAs, annual reports, and applicable 
supplements. Submissions in electronic format will help simplify and 
speed up our review of these documents. Currently, applicants may 
voluntarily submit such data in electronic form, but they are not 
required to do so. The rule will require all applicants with approved 
and new NDAs, BLAs, and ANDAs to convert the

[[Page 22374]]

content of labeling to an electronic format for submission. At this 
time, the type of electronic file format that we have the ability to 
accept for processing, reviewing, and archiving is PDF. Applicants that 
do not already have the capabilities to create PDF files will have to 
acquire the software and expertise to do so or make contractual 
arrangements to have documents converted.
    The economic burden on industry will include a one-time cost to 
acquire the appropriate computer software and train employees on its 
use. Applicants may also incur additional one-time costs to revise 
applications that have not had any labeling changes within the last few 
years to a format that can be converted to a PDF file. We do not know 
the number of applicants that currently have the capability to submit 
electronic files, nor do we have firsthand information on how labeling 
files are currently maintained or on how much time will be required to 
train employees on the software and new procedures. The following 
estimates, therefore, are based on agency experience with voluntary 
electronic submissions and with converting word processing files to PDF 
format. We request that interested parties submit comments on the 
accuracy of these estimates.
    We receive annually approximately 651 applications, 7,089 annual 
reports, and 1,625 supplements that contain labeling from approximately 
610 applicants. Based on our experience working with voluntary 
electronic submissions, we estimate that overall approximately 70 
percent of the applicants (427) already have the necessary software and 
trained personnel to comply with the proposed rule. The remaining 30 
percent of applicants (183) would need to purchase software, which 
costs about $250. Based on agency review, approximately 78 percent of 
these 183 applicants (143) would be considered small (fewer than 750 
employees for drug product manufacturers, fewer than 500 employees for 
biological product manufacturers). We estimate that each small 
applicant would need to purchase only one copy of the software, for a 
total of (143) copies. The remaining 22 percent of applicants (40) that 
would need to purchase software are large entities. The agency 
estimates that each of these firms would need to purchase about 3 
copies of the software, or 120 copies (40 x 3). Thus, the total one-
time cost for software is $65,750 ((143 + 120) x $250). Training costs 
include the cost of the software training course (estimated at $150 for 
a 6-hour course) and the wages of the employees attending the course 
(assuming an average weighted wage rate of $40 per hour). We estimate 
that applicants would train two employees per software purchase (526 
employees), for a total one-time cost of $205,140 ([($150 + (6 hours x 
$40)) x 526]). The total one-time cost for software and training 
combined is estimated to be $270,890 ($65,750 + $205,140).
    The cost to convert the applicable labeling to an electronic format 
is a one-time cost. The cost of conversions for new NDAs, BLAs, and 
ANDAs will be nominal because the file would be in a format easily 
convertible to PDF. We receive annually approximately 1,625 supplements 
that would be subject to the proposed rule. As the majority of products 
for which supplements are submitted would have had labeling changes 
within the last few years, most labeling files would be easily 
accessible and require an estimated 15 minutes to process. Thus, the 
total number of hours needed to convert applicable labeling in 
supplements to a PDF file format is 406. Labeling in all 7,089 annual 
reports would also need to be converted. The conversion of this 
labeling to a PDF file for about 20 percent of NDA annual reports 
(488), 30 percent of ANDA annual reports (1,365), and 20 percent of BLA 
annual reports (20) would require additional time to complete because 
they are not in a format easily convertible to PDF. We estimate that 
these annual reports would require 8 hours to complete, for a total of 
14,984 hours ((488 + 1,365 + 20) x 8). The remaining annual reports 
(5,216) would require 15 minutes, for a total of 1,304 hours. Thus, the 
total number of hours needed to convert applicable labeling to a PDF 
file format in annual reports is 16,188 (14,984 + 1,304). Using the 
weighted average wage rate ($40 per hour), the total one-time costs to 
convert applicable labeling in supplements and annual reports would be 
$663,760 ((406 + 16,188) x $40). The cost for the entire rule is 
estimated to be about $934,650 ($270,890 + $663,760).
    Approximately 300 domestic entities would be affected by this 
proposed rule, about 240 of which meet the Small Business 
Administration's definition of a small entity (fewer than 750 employees 
for drug product manufacturers, fewer than 500 employees for biological 
product manufacturers). The economic impact of this proposed rule would 
vary by firm depending on the number of applications they hold and 
whether or not the company has PDF capabilities. The number of 
applications per firm ranges from 1 to 124, with a median of 4 
applications per small entity. The average small entity has about seven 
applications, and, assuming each needed to purchase the software and 
train employees, this rule would cost the firm less than $1,000, or 
about $140 per application. Because these costs would almost certainly 
be less than 1 percent of product revenues, the agency certifies that 
this proposed rule will not, if finalized, have a significant economic 
impact on a substantial number of small entities.

X. Proposed Effective Date

    FDA proposes that any final rule that may issue regarding this 
proposal become effective 180 days after its date of publication in the 
Federal Register.

XI. Request for Comments

    Interested persons may submit to the Dockets Management Branch 
(address above) written or electronic comments regarding this proposal 
by August 1, 2002. Two copies of any comments are to be submitted, 
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 Dockets Management 
Branch between 9 a.m. and 4 p.m., Monday through Friday.

List of Subjects

21 CFR Part 314

    Administrative practice and procedure, Confidential business 
information, Drugs, Reporting and recordkeeping requirements.

21 CFR Part 601

    Administrative practice and procedure, Biologics, Confidential 
business information.

    Therefore, under the Federal Food, Drug, and Cosmetic Act, the 
Public Health Service Act, and under authority delegated to the 
Commissioner of Food and Drugs, it is proposed that 21 CFR parts 314 
and 601 be amended as follows:

PART 314--APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG

    1. The authority citation for 21 CFR part 314 is revised to read as 
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 356, 356a, 
356b, 356c, 371, 374, 379e.

    2. Section 314.50 is amended by revising paragraph (l)(1); by 
adding headings for paragraphs (l)(2), (l)(3), and (l)(4); by removing 
from paragraphs (l)(2) and (l)(3) the word ``shall'' and adding in its 
place the word ``must''; and by adding paragraph (l)(5) to read as 
follows:

[[Page 22375]]

Sec. 314.50  Content and format of an application.

* * * * *
    (l) Format of an original application. (1) Archival copy. The 
applicant must submit a complete archival copy of the application that 
contains the information required under paragraphs (a) through (f) of 
this section. FDA will maintain the archival copy during the review of 
the application to permit individual reviewers to refer to information 
that is not contained in their particular technical sections of the 
application, to give other agency personnel access to the application 
for official business, and to maintain in one place a complete copy of 
the application. Except as required by paragraph (1)(1)(i) of this 
section, applicants may submit the archival copy on paper or in 
electronic format provided that electronic submissions are made in 
accordance with part 11 of this chapter.
    (i) Labeling. The content of labeling required under 
Sec. 201.100(d)(3) of this chapter (commonly referred to as the package 
insert or professional labeling), including all text, tables, and 
figures, must be submitted to the agency in electronic format as 
described in paragraph (l)(5) of this section. This requirement is in 
addition to the requirements of paragraph (e)(2)(ii) of this section 
that copies of the formatted label and all labeling be submitted. 
Submissions under this paragraph must be made in accordance with part 
11 of this chapter, except for the requirements of Sec. 11.10(a), (c) 
through (h), and (k), and the corresponding requirements of Sec. 11.30.
    (ii) [Reserved]
    (2) Review copy. * * *
    (3) Field copy. * * *
    (4) Binding folders. * * *
    (5) Electronic format submissions. Electronic format submissions 
must be in a form that FDA can process, review, and archive. FDA will 
periodically issue guidance on how to provide the electronic submission 
(e.g., method of transmission, media, file formats, preparation and 
organization of files).
    3. Section 314.81 is amended by revising paragraph (b)(2)(iii) to 
read as follows:


Sec. 314.81  Other postmarketing reports.

* * * * *
    (b) * * *
    (2) * * *
    (iii) Labeling. (a) Currently used professional labeling, patient 
brochures or package inserts (if any), and a representative sample of 
the package labels.
    (b) The content of labeling required under Sec. 201.100(d)(3) of 
this chapter (i.e., the package insert or professional labeling), 
including all text, tables, and figures, must be submitted in 
electronic format. Electronic format submissions must be in a form that 
FDA can process, review, and archive. FDA will periodically issue 
guidance on how to provide the electronic submission (e.g., method of 
transmission, media, file formats, preparation and organization of 
files). Submissions under this paragraph must be made in accordance 
with part 11 of this chapter, except for the requirements of 
Sec. 11.10(a), (c) through (h), and (k), and the corresponding 
requirements of Sec. 11.30.
    (c) A summary of any changes in labeling that have been made since 
the last report listed by date in the order in which they were 
implemented, or if no changes, a statement of that fact.
* * * * *
    4. Section 314.94 is amended by revising paragraph (d)(1) to read 
as follows:


Sec. 314.94  Content and format of an abbreviated application.

* * * * *
    (d) * * * (1) The applicant must submit a complete archival copy of 
the abbreviated application as required under paragraphs (a) and (c) of 
this section. FDA will maintain the archival copy during the review of 
the application to permit individual reviewers to refer to information 
that is not contained in their particular technical sections of the 
application, to give other agency personnel access to the application 
for official business, and to maintain in one place a complete copy of 
the application.
    (i) Format of submission. An applicant may submit portions of the 
archival copy of the abbreviated application in any form that the 
applicant and FDA agree is acceptable, except as provided in paragraph 
(d)(1)(ii) of this section.
    (ii) Labeling. The content of labeling required under 
Sec. 201.100(d)(3) of this chapter (commonly referred to as the package 
insert or professional labeling), including all text, tables, and 
figures, must be submitted to the agency in electronic format as 
described in paragraph (d)(1)(iii) of this section. This requirement 
applies to the content of labeling for the proposed drug product only 
and is in addition to the requirements of paragraph (a)(8)(ii) of this 
section that copies of the formatted label and all proposed labeling be 
submitted. Submissions under this paragraph must be made in accordance 
with part 11 of this chapter, except for the requirements of 
Sec. 11.10(a), (c) through (h), and (k), and the corresponding 
requirements of Sec. 11.30.
    (iii) Electronic format submissions. Electronic format submissions 
must be in a form that FDA can process, review, and archive. FDA will 
periodically issue guidance on how to provide the electronic submission 
(e.g., method of transmission, media, file formats, preparation and 
organization of files).
* * * * *

PART 601--LICENSING

    5. The authority citation for 21 CFR part 601 continues to read as 
follows:

    Authority: 15 U.S.C. 1451-1561; 21 U.S.C. 321, 351, 352, 353, 
355, 356b, 360, 360c-360f, 360h-360j, 371, 374, 379e, 381; 42 U.S.C. 
216, 241, 262, 263, 264; sec. 122, Pub. L. 105-115, 111 Stat. 2322 
(21 U.S.C. 355 note).

    6. Add 601.14 to subpart C to read as follows:


Sec. 601.14  Regulatory submissions in electronic format.

    (a) General. Electronic format submissions must be in a form that 
FDA can process, review, and archive. FDA will periodically issue 
guidance on how to provide the electronic submission (e.g., method of 
transmission, media, file formats, preparation and organization of 
files.)
    (b) Labeling. The content of labeling required under 
Sec. 201.100(d)(3) of this chapter (commonly referred to as the package 
insert or professional labeling), including all text, tables, and 
figures, must be submitted to the agency in electronic format as 
described in paragraph (a) of this section. This requirement is in 
addition to the provisions of Secs. 601.2(a) and 601.12(f) that require 
applicants to submit specimens of the labels, enclosures, and 
containers, or to submit other final printed labeling. Submissions 
under this paragraph must be made in accordance with part 11 of this 
chapter except for the requirements of Sec. 11.10(a), (c) through (h), 
and (k), and the corresponding requirements of Sec. 11.30.

    Dated: April 26, 2002.
Lester M. Crawford,
Deputy Commissioner.

Tommy G. Thompson,
Secretary of Health and Human Services.
[FR Doc. 02-11039 Filed 5-1-02; 8:45 am]
BILLING CODE 4160-01-S