[Federal Register: December 4, 2007 (Volume 72, Number 232)]
[Proposed Rules]
[Page 68111-68113]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr04de07-23]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 210 and 211
[Docket No. 1995N-0362]
Current Good Manufacturing Practice; Amendment of Certain
Requirements For Finished Pharmaceuticals; Withdrawal
AGENCY: Food and Drug Administration, HHS
ACTION: Proposed rule; withdrawal.
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SUMMARY: The Food and Drug Administration (FDA) is announcing the
[[Page 68112]]
withdrawal of a proposed rule published in the Federal Register of May
3, 1996 (61 FR 20103) (the May 1996 proposed rule). The May 1996
proposed rule would have amended certain requirements of the current
good manufacturing practice (CGMP) regulations for finished
pharmaceuticals. These proposed changes would have clarified certain
manufacturing, quality control, and documentation requirements and
would have updated the requirements for process and methods validation.
In light of more recent scientific and technical advances and evolving
quality systems and risk management concepts, FDA concludes that, at
this time, it is appropriate to withdraw the May 1996 proposed rule and
newly evaluate the issues raised in that proposal.
DATES: The proposed rule is withdrawn on December 4, 2007.
FOR FURTHER INFORMATION CONTACT:
Mary Malarkey, Center for Biologics Evaluation and Research (HFM-
600), Food and Drug Administration, 1401 Rockville Pike, Rockville, MD
20852-1448, 301-827-6190, or
Dennis Bensley, Center for Veterinary Medicine (HFV-140), Food and
Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 301-827-
6956, or
Frederick Blumenschein, Center for Drug Evaluation and Research
(HFD-326), Food and Drug Administration, 11919 Rockville Pike,
Rockville, MD 20852, 301-827-9022.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of May 3, 1996 (61 FR 20103), FDA proposed
to amend certain requirements of the CGMP regulations for finished
pharmaceuticals in parts 210 and 211 (21 CFR parts 210 and 211) to
clarify certain manufacturing, quality control, and documentation
requirements so that the regulations would more accurately reflect the
prevailing CGMP. FDA received approximately 1,500 comments on the
proposed rule. (See section III of this document, Comments on the May
1996 Proposed Rule).
After publication of the May 1996 proposed rule, FDA began to
reconsider its approach to regulation of CGMP, consistent with changes
occurring in other industries and in other countries. This change in
approach is summarized in the following paragraphs.
In August 2002, FDA announced a significant new initiative to
enhance and modernize regulation of pharmaceutical manufacturing
quality, the Pharmaceutical CGMPs for the 21st Century initiative (21st
Century initiative). As a part of the 21st Century initiative, FDA
created a CGMP Harmonization Analysis working group to analyze internal
and external CGMP requirements, including those related to quality
systems. The working group performed a formal analysis of parts 210 and
211 compared with other regulations, such as the FDA Medical Device
Quality System Requirements, the FDA Food Hazard Analysis and Critical
Control Points requirements, and the drug GMPs of the European Union,
to identify the differences and consider the value of adding or
changing the current regulations in light of these more recently
developed and related product manufacturing standards.
Based on the working group's analysis, the agency decided that a
different approach to revising the CGMP regulations was appropriate,
and has decided to withdraw the proposed rule.
II. New Approach to Revising FDA's CGMP Regulations
The emphasis of the new approach to CGMP arising from the 21st
Century Initiative will be to encourage timely detection of and
response to emerging adverse trends or indications that product quality
has been compromised, to provide further clarity and modernize the
regulations, and to harmonize various aspects of parts 210 and 211 both
internationally and with other agency regulations.\1\
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\1\See Pharmaceutical CGMPs for the 21st Century--A Risk Based
Approach; Final Report, September, 2004; available at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/gmp/gmp2004/GMP_finalreport2004.htm
.
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The agency has determined that the current CGMP regulations (parts
210 and 211) provide a degree of flexibility that will permit the
agency to continue to modernize its approach to regulation of CGMP. The
agency has also concluded that, as stated in the final report on the
21st Century initiative, given this new approach to regulation of
pharmaceutical CGMP, it would be preferable to revise the CGMP
regulations in an incremental fashion, rather than using the
comprehensive approach taken in the May 1996 proposed rule. After
careful consideration, FDA concludes that at this time, it is
appropriate to withdraw the May 1996 proposed rule and newly evaluate
the issues raised in that proposal in the context of more recent
scientific and technical advances and quality systems and risk
management concepts.
We plan to revise the CGMP regulations using a more incremental
approach. As part of the FDA's incremental approach to revising our
CGMP regulations, we are publishing a direct final rule (and a
companion proposed rule) elsewhere in this issue of the Federal
Register that will, when finalized, clarify and modernize certain
provisions in parts 210 and 211. That direct final rule and proposed
rule include some of the minor changes to CGMP that were originally
proposed in 1996.
III. Comments on the May 1996 Proposed Rule
FDA received approximately 1,500 comments on the May 1996 proposed
rule from 116 pharmaceutical companies, attorneys, consultants, trade
associations, and generic companies. The most significant topics on
which FDA received comments are summarized as follows:
Approximately 298 comments addressed the proposed new
section on process validation (Sec. 211.220). The volume and variety
of comments and suggestions indicated to FDA that the new section, as
proposed, did not provide the clarification intended.
Approximately 102 comments were directed at the proposed
changes to Sec. 211.110 on sampling and testing of in-process
materials and drug products, which would have added new in-process
sampling and validation requirements with respect to blend uniformity.
The bulk of these comments questioned the need for additional testing
and sampling requirements in Sec. 211.110, because other sections of
the current rule already require scientifically sound sampling plans
and representative samples.
Approximately 112 comments discussed proposed revisions to
Sec. 211.192 on the production, control, and laboratory review, and
investigation of discrepancies. The May 1996 proposed rule required
written procedures to be established for the review of certain records
and investigation of unexplained discrepancies. Many of these comments
recommended that these investigations and reviews should be used to
proactively prevent (potential) future problems rather than being used
only to retroactively identify manufacturing discrepancies.
A number of comments to the rule were submitted by the
compressed medical gas industry, which communicated concerns regarding
the applicability to the compressed medical gas industry of the
proposed changes to CGMP.
[[Page 68113]]
Approximately 70 comments were received regarding the
proposed new Sec. 211.240 on control of chemical and physical
contaminants. Many of the comments stated that the rule should be
revised to better describe how contaminants will be identified and to
provide allowances for threshold levels or limits of contaminants.
Overall, the comments were constructive, informative, and addressed
nearly every area of the May 1996 proposed rule. Although we do not
plan to publish specific responses to each of these comments, we will
take these comments into account as we proceed to make incremental
changes to parts 210 and 211.
IV. Withdrawal of the Proposed Rule
For the reasons described in this document, FDA is withdrawing the
proposed rule published on May 3, 1996 (61 FR 20103).
Dated: November 26, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-23271 Filed 12-3-07; 8:45 am]
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