[Federal Register: September 5, 2003 (Volume 68, Number 172)]
[Notices]               
[Page 52777-52779]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr05se03-69]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2003D-0386]

 
Draft Guidance for Industry on Formal Dispute Resolution: 
Scientific and Technical Issues Related to Pharmaceutical Current Good 
Manufacturing Practice; Availability

AGENCY:  Food and Drug Administration, HHS.

ACTION:  Notice.

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SUMMARY:  The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance for industry entitled ``Formal Dispute 
Resolution: Scientific and Technical Issues Related to Pharmaceutical 
CGMP.'' In the draft guidance, the agency describes a formal, two-
tiered dispute resolution process intended to resolve disputes of 
scientific and technical issues relating to current good manufacturing 
practice (CGMP) that arise during FDA inspections of pharmaceutical 
manufacturers.

DATES: Submit written or electronic comments on the draft guidance by 
March 3, 2004. General comments on agency guidance documents are 
welcome at any time. Submit written or electronic comments on the 
collection of information by November 4, 2003.

ADDRESSES:  Submit written requests for single copies of the draft 
guidance to the Division of Drug Information (HFD-240), Center for Drug 
Evaluation and Research, Food and Drug Administration, 5600 Fishers 
Lane, Rockville, MD 20857; the Office of Communication, Training and 
Manufacturers Assistance (HFM-40), Center for Biologics Evaluation and 
Research, 1401 Rockville Pike, Rockville, MD 20852-1448; or 
Communications Staff (HFV-12), Center for Veterinary Medicine, 7519 
Standish Pl., Rockville, MD 20855. Send one self-addressed adhesive 
label to assist that office in processing your requests. See the 
SUPPLEMENTARY INFORMATION section for electronic access to the draft 
guidance document.
    Submit written comments on the draft guidance and on the collection 
of information to the Division of Dockets Management (HFA-305), Food 
and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 
20852. Submit electronic comments on the draft guidance and the 
collection of information to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments.

FOR FURTHER INFORMATION CONTACT: Mary Jane Mathews, Center for Drug 
Evaluation and Research (HFD-3), Food and Drug Administration, 1451 
Rockville Pike, Rockville, MD 20852, 301-594-2847.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Formal Dispute Resolution: Scientific and Technical Issues 
Related to Pharmaceutical CGMP.'' 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 the Office of Regulatory Affairs (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 dispute 
resolution process and met with stakeholders in December 2002 to seek 
their input.

[[Page 52778]]

    The draft 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 draft guidance 
describes a formal two-tiered dispute resolution process that provides 
a formal mechanism for requesting review and decision on issues that 
arise during inspections.
    [sbull] Tier-one of the dispute resolution process provides a 
mechanism to raise scientific or technical issues to the ORA and center 
levels.
    [sbull] Tier-two of the dispute resolution process provides a 
mechanism to raise scientific or technical issues to the agency's 
Dispute Resolution Panel for Scientific and Technical Issues Related to 
Pharmaceutical CGMP (DR Panel).
    The draft guidance also covers the following topics:
    [sbull] 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.
    [sbull] Instructions on how to submit requests for formal dispute 
resolution and a list of the supporting information that should 
accompany these requests.
    [sbull] Public availability of decisions reached during the dispute 
resolution process to promote consistent application and interpretation 
of drug quality-related regulations.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the agency's current thinking on ``Formal 
Dispute Resolution: Scientific and Technical Issues Related to 
Pharmaceutical CGMP.'' It does not create or confer any rights for or 
on any person and does not operate to bind FDA or the public. An 
alternative approach may be used if such approach satisfies the 
requirements of the applicable statutes and regulations.

II. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments on the draft guidance. 
Two copies of mailed 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. The 
draft guidance and received comments are available for public 
examination in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday.

III. The Paperwork Reduction Act of 1995

    Under the Paperwork Reduction Act (44 U.S.C. 3501-3520) (the PRA), 
Federal agencies must obtain approval from the Office of Management and 
Budget (OMB) for each collection of information they conduct or 
sponsor. ``Collection of information'' is defined in 44 U.S.C. 3502(3) 
and 5 CFR 1320.3(c) and includes agency requests or requirements that 
members of the public submit reports, keep records, or provide 
information to a third party. Section 3506(c)(2)(A) of the PRA (44 
U.S.C. 3506(c)(2)(A)) requires Federal agencies to provide a 60-day 
notice in the Federal Register concerning each proposed collection of 
information before submitting the collection to OMB for approval. To 
comply with this requirement, FDA is publishing notice of the proposed 
collection of information set forth in this document.
    With respect to the following collection of information, FDA 
invites comments on the following topics: (1) Whether the proposed 
collection of information is necessary for the proper performance of 
FDA's functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's 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 on respondents, including 
through the use of automated collection techniques, when appropriate, 
and other forms of information technology.
    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 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 
the ORA and center levels and for requesting review by 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 the Form FDA 483, the manufacturer can formally 
request dispute resolution and can use the formal two-tiered dispute 
resolution process described in the draft 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 a Form FDA 483, the 
manufacturer can file a written request for formal dispute resolution 
with the appropriate ORA unit as described in the draft guidance. The 
request for formal dispute resolution should be made within 10 days of 
the completion of an inspection, and should include all supporting 
documentation and arguments for review, as described. 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 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 draft guidance and 
include the following:
    [sbull] Cover sheet that clearly identifies the submission as 
either a request for tier-one dispute resolution or a request for tier-
two dispute resolution;
    [sbull] Name and address of manufacturer inspected (as listed on 
the Form FDA 483);
    [sbull] Date of inspection (as listed on the Form FDA 483);

[[Page 52779]]

    [sbull] Date the Form FDA 483 issued (from the Form FDA 483);
    [sbull] Firm establishment inventory (FEI) number, if available 
(from the Form FDA 483);
    [sbull] Names and titles of FDA employees who conducted inspection 
(from the Form FDA 483);
    [sbull] Office responsible for the inspection, e.g., district 
office, as listed on the Form FDA 483;
    [sbull] Application number if the inspection was a preapproval 
inspection;
    [sbull] Comprehensive statement of each issue to be resolved:
     [sbull] Identify the observation in dispute.
     [sbull] Clearly present the manufacturer's scientific position or 
rationale concerning the issue under dispute with any supporting data.
     [sbull] 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 Form FDA 483.
     [sbull] Identify possible solutions.
     [sbull] State expected outcome.
    [sbull] 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 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 dispute resolution. FDA also estimates that approximately five 
manufacturers will appeal approximately five 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 draft guidance. 
FDA requests comments on this analysis of information collection 
burdens.

                                                     Table 1.--Estimated Annual Reporting Burden\1\
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                                                                              Number of Responses per    Total Annual      Hours per
                                                      No. of Respondents            Respondent            Responses         Response       Total Hours
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Requests for Tier-One Dispute Resolution                                25                         1               25               30              750
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Requests for Tier-Two Dispute Resolution                                 5                         1                5                8               40
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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.

IV. Electronic Access

    Persons with access to the Internet may obtain the draft guidance 
document at either http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/index.htm or http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/default.htm
http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cber/guidelines.htm
    Dated: August 27, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 03-22575 Filed 9-3-03; 10:00 am]

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