[Federal Register: May 3, 2002 (Volume 67, Number 86)]
[Proposed Rules]
[Page 22367-22375]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr03my02-10]
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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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=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\
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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
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\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