[Federal Register: January 26, 2005 (Volume 70, Number 16)]
[Notices]               
[Page 3712-3714]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr26ja05-85]                         

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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of Management and Budget Review; Comment Request; Draft Guidance for 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 
February 25, 2005.

ADDRESSES: The Office of Management and Budget (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.

[[Page 3713]]


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.
    Title: Draft Guidance for Industry on Formal Dispute Resolution: 
Scientific and Technical Issues Related to Pharmaceutical CGMP
    Description: The draft guidance is intended to provide information 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 
draft guidance provides procedures that will encourage open and prompt 
discussion of disputes and lead to their resolution. The draft guidance 
describes procedures for raising such disputes to FDA's Office of 
Regulatory Affairs and center levels and for requesting review by the 
dispute resolution (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 before 
the issuance of the Form FDA 483, the manufacturer can formally request 
DR and can use the formal two-tiered DR process described in the draft 
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.
    If a manufacturer disagrees with the scientific or technical basis 
for an observation listed by an investigator on a Form FDA 483, the 
manufacturer can file a written request for formal DR with the 
appropriate ORA unit as described in the draft guidance. The request 
for formal DR should be made within 10 days of the completion of an 
inspection, and should include all supporting documentation and 
arguments for review, as described in the following paragraphs. If a 
manufacturer disagrees with the tier-one decision in the formal DR 
process, the manufacturer can file a written request for formal DR by 
the DR Panel. The manufacturer should provide the written request for 
formal DR 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 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 draft guidance and include the 
following:
     Cover sheet that clearly identifies the submission as 
either a request for tier-one DR or a request for tier-two DR;
     Name and address of manufacturer inspected (as listed on 
Form FDA 483);
     Date of inspection (as listed on Form FDA 483);
     Date the Form FDA 483 issued (from the Form FDA 483);
     FDA Establishment Identification (FEI) Number, if 
available (from Form FDA 483);
     FDA employee names and titles that conducted inspection 
(from Form FDA 483);
     Office responsible for the inspection, e.g., district 
office, as listed on the Form FDA 483;
     Application number if the inspection was a preapproval 
inspection;
     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 DR that may have occurred before the issuance of 
the Form FDA 483.
    Identify possible solutions.
    State expected outcome.
     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 DR under the draft 
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 draft 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 DR. FDA also estimates that approximately five manufacturers 
will appeal approximately five of these requests to the DR Panel 
(request for tier-two DR).
    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 DR and approximately 8 
hours to prepare and submit each request for a tier-two DR.
    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 DR and requests for a 
tier-two DR under the draft guidance.

                                      Estimated Annual Reporting Burden\1\
----------------------------------------------------------------------------------------------------------------
                   No. of        No. of Responses  per      Total Annual        Hours per
                Respondents            Respondent            Responses           Response         Total Hours
----------------------------------------------------------------------------------------------------------------
Requests             25                               1                 25                 30                750
 for Tier-
 One
 Dispute
 Resolution
----------------------------------------------------------------------------------------------------------------

[[Page 3714]]


>Requests                    5                        1                  5                  8                 40
 for Tier-
 Two
 Dispute
 Resolution
----------------------------------------------------------------------------------------------------------------
Total                                                                                                        790
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection.

    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 notice requested comments on the information 
collection estimates within 60 days. 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 draft guidance.
    The draft guidance was drafted as part of FDA's 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 
DR 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 DR process and met with stakeholders in 
December 2002 to seek their input.
    The draft 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 draft guidance describes a formal 
two-tiered DR process that provides a formal mechanism for requesting 
review and decision on issues that arise during inspections:
     Tier-one of the DR process provides a mechanism to raise 
scientific or technical issues to the ORA and center levels.
     Tier-two of the DR process provides a mechanism to raise 
scientific or technical issues to the agency's DR Panel for Scientific 
and Technical Issues Related to Pharmaceutical CGMP (DR Panel).
    The draft guidance also covers the following topics:
     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.
     Instructions on how to submit requests for formal DR and a 
list of the supporting information that should accompany these 
requests.
     Public availability of decisions reached during the DR 
process to promote consistent application and interpretation of drug 
quality-related regulations.

    Dated: January 18, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-1396 Filed 1-25-05; 8:45 am]

BILLING CODE 4160-01-S