[Federal Register Volume 72, Number 232 (Tuesday, December 4, 2007)]
[Proposed Rules]
[Pages 68111-68113]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-23271]


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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DATES: The proposed rule is withdrawn on December 4, 2007.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://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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