[Federal Register Volume 73, Number 148 (Thursday, July 31, 2008)]
[Notices]
[Pages 44749-44751]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-17577]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-N-0047] (formerly Docket No. 2008N-0005)


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Formal Dispute 
Resolution: Scientific and Technical Issues Related to Pharmaceutical 
Current Good Manufacturing Practice

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

DATES: Fax written comments on the collection of information by 
September 2, 2008.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
FAX: 202-395-6974, or e-mailed to <a href="/cdn-cgi/l/email-protection#791b181e0c1015180b3916141b571c1609571e160f"><span class="__cf_email__" data-cfemail="55373432203c393427153a38377b303a257b323a23">[email protected]</span></a>. All comments 
should be identified with the OMB control number 0910-0563. Also 
include the FDA docket number found in brackets in the heading of this 
document.

FOR FURTHER INFORMATION CONTACT: Elizabeth Berbakos, Office of 
Information Management (HFA-710), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-796-3792.

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

Formal Dispute Resolution: Scientific and Technical Issues Related to 
Pharmaceutical Current Good Manufacturing Practice--(OMB Control Number 
0910-0563)--Extension

    The guidance is intended to provide information to manufacturers of 
veterinary and human drugs, including human biological drug products, 
on how to resolve disputes of scientific and technical issues relating 
to Current Good Manufacturing Practice (CGMP). Disputes related to 
scientific and technical issues may arise during FDA inspections of 
pharmaceutical manufacturers to determine compliance with CGMP 
requirements, or during FDA's assessment of corrective actions 
undertaken as a result of such inspections. The guidance provides 
procedures that encourage open and prompt discussion of disputes and 
lead to their resolution. The guidance describes procedures for raising 
such disputes to the Office of Regulatory Affairs (ORA) and center 
levels and for requesting review by the dispute resolution (DR) Panel 
(the DR Panel).
    When a scientific or technical issue arises during an FDA 
inspection, the manufacturer should initially attempt to reach 
agreement on the issue informally with the investigator. Certain 
scientific or technical issues may be too complex or time-consuming to 
resolve during the inspection. If resolution of a scientific or 
technical issue is not accomplished through informal mechanisms prior 
to the issuance of Form FDA 483, the manufacturer can formally request 
DR and can use the formal two-tiered DR process described in the 
guidance.
    Tier-one of the formal DR process involves scientific or technical 
issues raised by a manufacturer to the ORA and center levels. If a 
manufacturer disagrees with the tier-one decision, tier two of the 
formal DR process would then be available for appealing that decision 
to the DR Panel.
    The written request for formal DR to the appropriate ORA unit 
should be made within 30 days of the completion of an inspection, and 
should include all supporting documentation and arguments for review, 
as described below. The written request for formal DR to the DR Panel 
should be made within 60 days of receipt of the tier-one decision, and 
should include all supporting documentation and arguments, as described 
in the following paragraphs.
    All requests for formal DR should be in writing and include 
adequate information to explain the nature of the dispute and to allow 
FDA to act quickly and efficiently. Each request should be sent to the 
appropriate address listed in the guidance and include the following:
    <bullet> Cover sheet that clearly identifies the submission as 
either a request for tier-one DR or a request for tier-two DR;
    <bullet> Name and address of manufacturer inspected (from Form FDA 
483);

[[Page 44750]]

    <bullet> Date of inspection (from Form FDA 483);
    <bullet> Date the Form FDA 483 issued (from Form FDA 483);
    <bullet> FEI Number, if available (from Form FDA 483);
    <bullet> FDA employee names and titles that conducted inspection 
(from Form FDA 483);
    <bullet> Office responsible for the inspection, e.g., district 
office (from Form FDA 483);
    <bullet> Application number if the inspection was a preapproval 
inspection;
    <bullet> Comprehensive statement of each issue to be resolved;
    <bullet> Identify the observation in dispute;
    <bullet> Clearly present the manufacturer's scientific position or 
rationale concerning the issue under dispute with any supporting data;
    <bullet> State the steps that have been taken to resolve the 
dispute, including any informal DR that may have occurred before the 
issuance of Form FDA 483;
    <bullet> Identify possible solutions;
    <bullet> State expected outcome;
    <bullet> Name, title, telephone and fax number, and e-mail address 
(as available) of manufacturer contact.
    The guidance was part of the FDA initiative ``Pharmaceutical cGMPs 
for the 21st Century: A Risk-Based Approach,'' which was announced in 
August 2002. The initiative focuses on FDA's current CGMP program and 
covers the manufacture of veterinary and human drugs, including human 
biological drug products. The agency formed the Dispute Resolution 
Working Group comprising representatives from ORA, the Center for Drug 
Evaluation and Research (CDER), the Center for Biologics Evaluation and 
Research (CBER), and the Center for Veterinary Medicine (CVM). The 
working group met weekly on issues related to the DR process and met 
with stakeholders in December 2002 to seek their input.
    The guidance was initiated in response to industry's request for a 
formal DR process to resolve differences related to scientific and 
technical issues that arise between investigators and pharmaceutical 
manufacturers during FDA inspections of foreign and domestic 
manufacturers. In addition to encouraging manufacturers to use 
currently available DR processes, the guidance describes the formal 
two-tiered DR process explained previously in this document. The 
guidance also covers the following topics:
    <bullet> The suitability of certain issues for the formal DR 
process, including examples of some issues with a discussion of their 
appropriateness for the DR process.
    <bullet> Instructions on how to submit requests for formal DR and a 
list of the supporting information that should accompany these 
requests.
    <bullet> Public availability of decisions reached during the 
dispute resolution process to promote consistent application and 
interpretation of drug quality-related regulations.
    Description of Respondents: Pharmaceutical manufacturers of 
veterinary and human drug products and human biological drug products.
    Burden Estimate: Based on the number of requests for tier-one and 
tier-two DR received by FDA since the guidance published in January 
2006, FDA estimates that approximately two manufacturers will submit 
approximately two requests annually for a tier-one DR, and that there 
will be one appeal of these requests to the DR Panel (request for tier-
two DR). FDA estimates that it will take manufacturers approximately 30 
hours to prepare and submit each request for a tier-one DR, and 
approximately 8 hours to prepare and submit each request for a tier-two 
DR. Table 1 of this document provides an estimate of the annual 
reporting burden for requests for tier-one and tier-two DRs.

                                                      Table 1--Estimated Annual Reporting Burden\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                              No. of         Annual Frequency       Total Annual        Hours Per
                                                           Respondents         per Response          Responses           Response         Total Hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
Requests for Tier-One DR                                                2                     1                  2                 30                 60
--------------------------------------------------------------------------------------------------------------------------------------------------------
Requests for Tier-Two DR                                                1                     1                  1                  8                  8
--------------------------------------------------------------------------------------------------------------------------------------------------------
Total                                                                                                                                                 68
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    In the Federal Register of January 22, 2008 (73 FR 3729), FDA 
published a 60-day notice requesting public comment on the information 
collection provisions. We received one comment in response to the 
January 22, 2008, Federal Register notice. The comment asked 3 
questions about the DR process set forth in the guidance.
    First, the comment asked how many working days are taken by the ORA 
and center levels to reach a decision after receipt of a request for 
tier-one DR.
    FDA Response--As explained in Section III.A of the guidance, if the 
ORA unit agrees with the manufacturer, the ORA unit will issue a 
written response to the manufacturer within 30 days of receipt of the 
request, noting its agreement with the manufacturer and resolution of 
the dispute. If the ORA unit disagrees with the manufacturer, the ORA 
unit will issue a written response to the manufacturer generally within 
30 days of receipt of the request, and if the ORA unit is unable to 
complete its review of the request and respond within 30 days, the ORA 
unit will notify the manufacturer, explain the reason for the delay 
(which may include the need for an additional 30 days for center 
review), and discuss the time frame for completing the review.
    Second, the comment asked how many working days are taken by the DR 
Panel to reach a decision after receipt of a request for tier-two DR.
    FDA Response--As explained in Section III.B of the guidance, if the 
DR Panel determines that the request is appropriate for review, it will 
schedule a meeting to discuss the issue within 90 days. If the DR Panel 
agrees with the manufacturer on the issue, the executive secretary of 
the DR Panel will issue a written response to the manufacturer within 
30 days of the meeting, noting its agreement with the manufacturer and 
resolution of the dispute. If the DR Panel disagrees with the 
manufacturer on the issue, the executive secretary of the DR Panel will 
issue a written response to the manufacturer within 30 days of the 
meeting, noting its decision on the issue. If the DR Panel determines 
that the request does not qualify for review, the executive secretary 
of the DR Panel will notify the manufacturer in writing within 30 days 
of receipt of the appeal. If FDA is unable to complete its review of 
the request and respond within 30 days, the executive secretary of the 
DR Panel will notify the

[[Page 44751]]

manufacturer, explain the reasons for the delay, and discuss the time 
frame for completing the review.
    Third, the comment asked whether ``the manufacturing facility is 
approvable or to be re-inspected'' if the dispute is not resolved at 
the end of the tier-two DR stage.
    FDA Response--As described in the guidance, it is FDA's intention 
to resolve through the DR process all issues raised by the 
manufacturer. If FDA agrees with the manufacturer, the Form FDA 483 
that prompted the request for formal dispute resolution would be 
revised or rescinded. If FDA disagrees with the manufacturer's request, 
the issues raised in the Form FDA 483 stand and FDA would expect 
compliance with the applicable CGMP requirements, which FDA may verify 
by re-inspection.

    Dated: July 25, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-17577 Filed 7-30-08; 8:45 am]
BILLING CODE 4160-01-S


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