[Federal Register Volume 70, Number 49 (Tuesday, March 15, 2005)]
[Notices]
[Pages 12697-12699]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-5027]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2003D-0386]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Guidance for Industry 
on 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 April 
14, 2005.

ADDRESSES: OMB is still experiencing significant delays in the regular 
mail, including first class and express mail, and messenger deliveries 
are not being accepted. 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: Fumie 
Yokota, Desk Officer for FDA, FAX: 202-395-6974.

FOR FURTHER INFORMATION CONTACT: Karen L. Nelson, Office of Management 
Programs (HFA-250), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857, 301-827-1482.

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.
    FDA previously issued this proposed collection of information in 
the Federal Register of January 26, 2005 (70 FR 3712). On February 24, 
2005 (70 FR 9083), FDA withdrew the proposed collection of information 
to correct the title from ``Draft Guidance for Industry on Formal 
Dispute Resolution: Scientific and Technical Issues Related to 
Pharmaceutical Current Good Manufacturing Practice'' to ``Guidance for 
Industry on Formal Dispute Resolution: Scientific and Technical Issues 
Related to Pharmaceutical Current Good Manufacturing Practice.''
    Title: Guidance for Industry on Formal Dispute Resolution: 
Scientific and Technical Issues Related to Pharmaceutical Current Good 
Manufacturing Practice
    Description: 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 practices (CGMPs). 
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 will 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 Panel for Scientific and Technical Issues Related to 
Pharmaceutical CGMP (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 the FDA 483, the manufacturer can formally request 
dispute resolution and can use the formal two-tiered dispute resolution 
process described in the guidance.
    Tier-one of the formal dispute resolution 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 dispute resolution process would then be 
available for appealing that decision to the DR Panel.
    If a manufacturer disagrees with the scientific or technical basis 
for an observation listed by an investigator on an FDA 483, the 
manufacturer can file a written request for formal dispute resolution 
with the appropriate ORA unit as described in the guidance. The request 
for formal dispute resolution should be made within 30 days of the 
completion of an inspection, and should include all supporting 
documentation and arguments for review, as described later in this 
document. If a manufacturer disagrees with the tier-one decision in the 
formal dispute resolution process, the manufacturer can file a written 
request for formal dispute resolution by

[[Page 12698]]

the DR Panel. The manufacturer should provide the written request for 
formal dispute resolution and all supporting documentation and 
arguments, as described in the following paragraphs, to the DR Panel 
within 60 days of receipt of the tier-one decision.
    All requests for formal dispute resolution 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:
    1. Cover sheet that clearly identifies the submission as either a 
request for tier-one dispute resolution or a request for tier-two 
dispute resolution;
    2. Name and address of manufacturer inspected (as listed on Form 
FDA 483);
    3. Date of inspection (as listed on FDA 483);
    4. Date the Form FDA 483 issued (from the Form FDA 483);
    5. FEI Number, if available (from FDA 483);
    6. FDA employee names and titles that conducted inspection (from 
FDA 483);
    7. Office responsible for the inspection, e.g., district office, as 
listed on the Form FDA 483;
    8. Application number if the inspection was a preapproval 
inspection;
    9. Comprehensive statement of each issue to be resolved:
     Identify the observation in dispute.
     Clearly present the manufacturer's scientific position or 
rationale concerning the issue under dispute with any supporting data.
     State the steps that have been taken to resolve the 
dispute, including any informal dispute resolution that may have 
occurred before the issuance of the FDA 483.
     Identify possible solutions.
     State expected outcome.
    10. Name, title, telephone and fax number, and e-mail address (as 
available) of manufacturer contact.
    Description of Respondents: Pharmaceutical manufacturers of 
veterinary and human drug products and human biological drug products.
    Burden Estimate: FDA has reviewed the total number of informal 
disputes that currently arise between manufacturers and investigators 
(and FDA district offices) when a manufacturer disagrees with the 
scientific or technical basis for an observation listed on a Form FDA 
483. FDA estimates that approximately 12 such disputes occur annually. 
FDA believes that the number of requests for formal dispute resolution 
under the guidance would be higher because manufacturers have expressed 
reluctance to dispute with the agency scientific or technical issues 
raised in an investigation in the absence of a formal mechanism to 
resolve the dispute. In addition, manufacturers have requested the 
formal mechanisms in the guidance to facilitate the review of such 
disagreements. Therefore, FDA estimates that approximately 25 
manufacturers will submit approximately 25 requests annually for a 
tier-one dispute resolution. FDA also estimates that approximately 5 
manufacturers will appeal approximately 5 of these requests to the DR 
Panel (request for tier-two dispute resolution).
    Based on the time it currently takes manufacturers to prepare 
responses to FDA concerning issues raised in a Form FDA 483, FDA 
estimates that it will take manufacturers approximately 30 hours to 
prepare and submit each request for a tier-one dispute resolution and 
approximately 8 hours to prepare and submit each request for a tier-two 
dispute resolution.
    Based on the methodology and assumptions in the previous 
paragraphs, table 1 of this document provides an estimate of the annual 
reporting burden for requests for a tier-one dispute resolution and 
requests for a tier-two dispute resolution under the guidance.

                                 Table 1.--Estimated Annual Reporting Burden\1\
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                         No. of        No. of Responses     Total Annual        Hours per
                      Respondents       per Respondent       Responses           Response         Total Hours
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Requests for Tier-                25                  1                 25                 30                750
 One Dispute
 Resolution
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Requests for Tier-                 5                  1                  5                  8                 40
 Two Dispute
 Resolution
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Total                                                                                                        790
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    In the Federal Register of September 5, 2003 (68 FR 52777), FDA 
announced the availability of a draft guidance for industry entitled 
``Formal Dispute Resolution: Scientific and Technical Issues Related to 
Pharmaceutical CGMP.'' The document requested comments within 60 days 
on the information collection estimates. No comments were received on 
the information collection estimates. This document requests comments 
on the information collection burden that FDA estimates will result 
from the final guidance.
    The guidance was drafted as 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, the Center for Biologics 
Evaluation and Research, and the Center for Veterinary Medicine. The 
working group met weekly on issues related to the dispute resolution 
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 dispute resolution 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 dispute resolution processes, the guidance 
describes a formal two-tiered dispute resolution process that provides 
a formal mechanism for requesting

[[Page 12699]]

review and decision on issues that arise during inspections:
     Tier-one of the dispute resolution process provides a 
mechanism to raise scientific or technical issues to the ORA and center 
levels,
     Tier-two of the dispute resolution process provides a 
mechanism to raise scientific or technical issues to the agency's DR 
Panel.
The guidance also covers the following topics:
     The suitability of certain issues for the formal dispute 
resolution process, including examples of some issues with a discussion 
of their appropriateness for the dispute resolution process,
     Instructions on how to submit requests for formal dispute 
resolution and a list of the supporting information that should 
accompany these requests, and
     Public availability of decisions reached during the 
dispute resolution process to promote consistent application and 
interpretation of drug quality-related regulations.

    Dated: March 9, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-5027 Filed 3-14-05; 8:45 am]
BILLING CODE 4160-01-S