[Federal Register Volume 71, Number 189 (Friday, September 29, 2006)]
[Notices]
[Pages 57548-57549]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-15966]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket Nos. 1999D-0054, 2001D-0475, and 2003D-0364] (formerly Docket 
Nos. 99D-0054, 01D-0475, and 03D-0364, respectively)


Guidances on Providing Regulatory Submissions in Electronic 
Format; Withdrawal of Guidances

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; withdrawal.

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SUMMARY: The Food and Drug Administration's (FDA) Center for Drug 
Evaluation and Research is announcing the withdrawal of three guidances 
for industry: ``Providing Submissions in Electronic Format--NDAs,'' 
``Providing Regulatory Submissions in Electronic Format--ANDAs,'' and 
``Providing Regulatory Submissions in Electronic Format: Annual Reports 
for NDAs and ANDAs.'' These guidances are being withdrawn because they 
are no longer consistent with more recent guidance and no longer 
reflect the agency's preferred format for receiving electronic 
submissions.

DATES: September 29, 2006.

FOR FURTHER INFORMATION CONTACT: Armando Oliva, Center for Drug 
Evaluation and Research (HF-18), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-1512, e-mail: 
[email protected], or
    Robert Yetter, Center for Biologics Evaluation and Research (HFM-
25), Food and Drug Administration, 1401

[[Page 57549]]

Rockville Pike, Rockville, MD 20852, 301-827-0373, e-mail: 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    During the past decade, FDA has been working to expand its ability 
to receive and review marketing applications electronically. In 
addition, the agency has been working through the International 
Conference on Harmonisation of Technical Requirements for Registration 
of Pharmaceuticals for Human Use (ICH) to harmonize the formats being 
used for marketing applications.
    Beginning in 1999, FDA issued two guidances and one draft guidance 
for industry that made recommendations to applicants wishing to submit 
applications to FDA in electronic format: (1) ``Providing Regulatory 
Submissions in Electronic Format--NDAs'' (e-NDA guidance) (64 FR 4432, 
January 28, 1999), (2) ``Providing Regulatory Submissions in Electronic 
Format--ANDAs'' (e-ANDA guidance) (67 FR 43331, June 27, 2002), and (3) 
``Providing Regulatory Submissions in Electronic Format--Annual Reports 
for New Drug Applications and Abbreviated New Drug Applications'' 
(draft) (68 FR 51788, August 28, 2003). In general, these guidances 
recommended submitting documents as portable document files (PDF), 
electronic data/case report tabulations as SAS transport files, and the 
NDA table of contents in PDF format. In the meantime, however, the FDA 
adopted the ICH Common Technical Document (CTD) headings and 
subheadings for marketing applications. ICH then issued specifications 
for the electronic version of the CTD (e-CTD).
    In October 2005, FDA issued the guidance ``Providing Regulatory 
Submissions in Electronic Format--Human Pharmaceutical Product 
Applications and Related Submissions Using the e-CTD Specifications'' 
(the e-CTD guidance) (70 FR 60842; October 19, 2005). This guidance 
differs from the e-NDA and e-ANDA guidances in one significant aspect: 
The application table of contents is no longer submitted as a PDF file, 
but is submitted as an XML (extensible markup language) file. This XML 
file has numerous advantages over the older PDF format, most 
significant of which is the ability to update the application table of 
contents automatically as new amendments are received. With the e-CTD 
format, sponsors and reviewers now have access to a real-time, up-to-
date, cumulative table of contents that provides easy and immediate 
access to all files included in an application, regardless of when they 
were included, or in what submission they are located. This has never 
previously been possible. Another advantage is that the table of 
contents can be displayed in various ways, allowing discipline-specific 
views of an application, further promoting review efficiency. This is 
especially important for agency review staff. For example, although all 
portions of an application are always available to all reviewers, a 
chemist would be interested in different portions of the application 
than a clinical reviewer. The XML table of contents permits reviewers 
to view the application in a manner that makes the most sense to 
support their particular review activity.
    Despite the release of the e-CTD guidance describing the use of the 
XML format, FDA has continued to make all three guidances available 
with their differing recommendations. As a result, applicants have had 
three choices when submitting a marketing application electronically: 
(1) Use the e-NDA/e-ANDA format, (2) use the e-CTD format, or (3) use 
what we call a ``hybrid'' submission (the older e-NDA format with the 
table of contents organized using the newer CTD headings). In addition, 
FDA still receives submissions that are a combination of paper and 
electronic formats. Of course, this would not be appropriate for 
sponsors who are using the e-CTD format, as doing this would negate the 
intent of having all portions of the application readily available for 
review via the XML table of contents. A result of having this variety 
of choices is confusion and frustration for industry, who are not 
receiving consistent recommendations about how to submit marketing 
applications. It is also confusing and frustrating for our review 
staff. In addition, our willingness to receive applications in a 
variety of different forms has forced the agency to maintain expensive 
and duplicative processes and systems for receiving and archiving these 
various application types.

II. Withdrawal of Guidances

    The e-CTD format is preferred by FDA because it is more efficient 
than the other choices and consistent with FDA's technical 
capabilities. The e-CTD format is also the preferred ICH format. As a 
result, the agency is withdrawing the earlier guidances. In addition, 
we will remove references to these guidances from the electronic 
submissions docket on December 31, 2007. Further information on 
providing regulatory submissions in electronic format can be found on 
Docket No. 1992S-0251 (formerly Docket No. 92S-0251) (http://www.fda.gov/ohrms/dockets/dockets/92s0251/92s0251.htm). We are 
recommending that sponsors wishing to submit applications 
electronically use the most efficient and internationally agreed to 
formats recommended in our most recent guidance.
    Although the Center for Biologics Evaluation and Research (CBER) 
supports the use of the e-CTD format and encourages its sponsors to use 
this format when creating its submissions, CBER also recognizes that in 
certain situations a sponsor may not be capable of providing 
submissions in that format at this time. Therefore, CBER recommends 
that sponsors who cannot use the e-CTD format consult guidance for 
industry ``Providing Regulatory Submissions to the Center for Biologics 
Evaluation and Research (CBER) in Electronic Format--Biologics 
Marketing Applications [Biologics License Application (BLA), Product 
License Application (PLA) / Establishment License Application (ELA) and 
New Drug Application (NDA)] (11/12/1999) (available online at http://www.fda.gov/cber/esub/esubguid.htm).

    Dated: September 22, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6-15966 Filed 9-28-06; 8:45 am]
BILLING CODE 4160-01-S