[Federal Register: March 15, 2005 (Volume 70, Number 49)]
[Notices]
[Page 12697-12699]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr15mr05-99]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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to correct the title from ``Draft Guidance for Industry on Formal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\
----------------------------------------------------------------------------------------------------------------
No. of No. of Responses Total Annual Hours per
Respondents per Respondent Responses Response Total Hours
----------------------------------------------------------------------------------------------------------------
Requests for Tier- 25 1 25 30 750
One Dispute
Resolution
----------------------------------------------------------------------------------------------------------------
Requests for Tier- 5 1 5 8 40
Two Dispute
Resolution
----------------------------------------------------------------------------------------------------------------
Total 790
----------------------------------------------------------------------------------------------------------------
\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