[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Draft Guidance for Industry on Formal Dispute Resolution: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availability of a draft guidance for industry entitled ``Formal Dispute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 In the draft guidance, the agency describes a formal, two-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DATES: Submit written or electronic comments on the draft guidance by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ADDRESSES: Submit written requests for single copies of the draft
guidance to the Division of Drug Information (HFD-240), Center for Drug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SUPPLEMENTARY INFORMATION section for electronic access to the draft
guidance document.
Submit written comments on the draft guidance and on the collection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 Submit electronic comments on the draft guidance and the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://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://www.fda.gov/cder/guidance/index.htm or http://www.fda.gov/ohrms/dockets/default.htm
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]
BILLING CODE 4160-01-S