[Federal Register: January 5, 2007 (Volume 72, Number 3)]
[Notices]
[Page 574-576]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr05ja07-46]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2006N-0525]
Supplements and Other Changes to an Approved Application; Public
Meeting
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of public meeting.
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SUMMARY: The Food and Drug Administration (FDA) is announcing a public
meeting to solicit comments on issues that FDA should consider when
developing revisions to its regulations regarding chemistry,
manufacturing, and controls (CMC) supplements and other changes to
approved marketing applications for human drugs. FDA is evaluating how
it could revise its regulations to allow for consideration of risk-
based approaches based on manufacturing process understanding,
including prior knowledge of similar products, and overall quality
systems to provide an enhanced risk-based approach to the CMC
regulatory process, which would reduce the number of supplements. We
will consider the input from the public meeting and comments on the
issues presented in this document as we consider whether to revise our
regulations.
DATES: The public meeting will be held on February 7, 2007, from 8:30
a.m. to 3:30 p.m. Anyone who wishes to speak at the meeting must
register and submit a summary of the presentation by January 24, 2007,
and submit an electronic copy of the presentation by January 31, 2007.
See section III of the SUPPLEMENTARY INFORMATION section of this
document for details on how to register. Submit written or electronic
comments by March 7, 2007.
ADDRESSES: The public meeting will be held at the Food and Drug
Administration, Center for Drug Evaluation and Research Conference
Room, 7519 Standish Pl., third floor, rm. A, Rockville, MD 20855. There
is parking near the building. Photo identification is required to clear
building security.
Submit written comments to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. Submit electronic comments 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: David J. Cummings, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 21, rm. 3525, Rockville, MD 20993-0002, 301-796-
2400, e-mail: David.Cummings@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of June 28, 1999 (64 FR 34608), FDA
published a proposed rule to implement section 116 of the Food and Drug
Administration Modernization Act (FDAMA)\1\ by amending certain
regulations including Sec. 314.70 (21 CFR 314.70) regarding
supplements and other changes to approved human new drug and
abbreviated new drug marketing applications. In the Federal Register of
April 8, 2004 (69 FR 18728), FDA published the final rule (final rule)
implementing these changes. Section 314.70, as amended, requires
manufacturers to assess the effects of manufacturing changes on the
identity, strength, quality, purity, and potency of a drug as those
factors relate to the safety or effectiveness of the product, and
categorizes all changes beyond the established variations in an
approved NDA or ANDA into one of three groups--major, moderate, or
minor. Major changes require an applicant to submit and receive FDA
approval of a supplement before distribution of the product made with
the manufacturing change. Moderate changes require an applicant to
submit a supplement at least 30 days before distribution of the product
or, in some cases, submit a supplement at the time of distribution.
Minor changes require an applicant to notify FDA of the changes in an
annual report.
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\1\ Section 116 of FDAMA (Public Law 105-115) amended the
Federal Food, Drug, and Cosmetic Act (FDCA) by adding section 506A
(21 U.S.C. 356a), which describes requirements and procedures for
making and reporting manufacturing changes to certain approved
marketing applications, including new drug applications (NDAs) and
abbreviated new drug applications (ANDAs).
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In August 2002, FDA introduced the Pharmaceutical Current Good
Manufacturing Practices (CGMPs) for the 21st Century Initiative (CGMP
Initiative, available on the Internet at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/gmp/index.htm
) to enhance and modernize the regulation of pharmaceutical
manufacturing and product quality. In September 2004 (after publication
of the final rule), FDA published a final report on ``Pharmaceutical
CGMPs for the 21st Century--A Risk-Based Approach'' (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
). As explained in
the report, FDA regulates pharmaceutical manufacturing to ensure that
the drug supply in the United States is of consistently high quality.
Because of critical public health implications of drug manufacturing,
FDA traditionally has exercised extensive control over virtually every
aspect of the manufacturing process. This regulatory approach has
contributed to pharmaceutical companies being reluctant to change their
manufacturing processes and equipment. In recent years, significant
advances in pharmaceutical manufacturing science, modern quality
management systems, and risk management approaches have taken place.
This has yielded new tools that
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can be used to help ensure manufacturing quality. The new tools enable
manufacturers to detect, analyze, correct, and prevent problems and
continuously improve their manufacturing processes. It has been the
goal of the CGMP Initiative to create a regulatory paradigm that will
encourage pharmaceutical manufacturers to use these new tools to
facilitate their decision making and implementation of manufacturing
processes to reliably produce pharmaceuticals of high quality. Under
the new paradigm, as under the current scheme, pharmaceutical
manufacturers are ultimately responsible for ensuring the quality of
their products subject to FDA regulatory oversight.
The current Sec. 314.70 categorizes postapproval CMC changes and
their associated reporting requirements without consideration of the
applicant's risk management activities or internal quality systems and
practices; therefore, Sec. 314.70 reflects a rules-based, or
prescriptive, approach to regulating postapproval manufacturing
changes. The current Sec. 314.70 may create regulatory burdens and
costs that discourage beneficial manufacturing changes and may not
support a desirable level of innovation, modernization, and flexibility
for the industry as described in the CGMP Initiative.
Consistent with the agency's risk-based approach to regulating
pharmaceutical manufacturing described in the CGMP Initiative, FDA is
considering possible revisions to Sec. 314.70. In particular, FDA is
evaluating how it could revise Sec. 314.70 to allow for more
manufacturing changes to be made without prior FDA approval using a
firm's internal change control system. FDA also is evaluating how it
could revise Sec. 314.70 to allow for consideration of risk-based
approaches based on manufacturing process understanding, including
prior knowledge of similar products, and overall quality systems to
provide an enhanced risk-based approach to the CMC regulatory process.
To accomplish this objective, FDA is considering redefining what FDA
considers to be a major manufacturing change, reducing the reporting
burden for certain changes, and creating a new reporting category of
manufacturing changes that do not require notification to FDA. FDA
anticipates that these revisions would reduce the number of
postapproval supplements that are required to be submitted. We
emphasize that under a new regulatory scheme, although the reporting
burdens for certain manufacturing changes would be reduced,
manufacturers will continue to be responsible for ensuring product
quality. FDA also is considering an approach that would retain aspects
of the current regulatory scheme to accommodate those manufacturers who
choose to continue operating within the current regulatory framework.
FDA is announcing this public meeting to solicit comments on issues
that should be considered if FDA decides to propose revisions to Sec.
314.70.
II. Questions for Discussion and Comment
FDA has prepared the following questions to help focus the comments
that will be presented at the public meeting or otherwise communicated
to the agency. Those who comment are invited to address any or all of
these questions, or raise other issues.
1. Is it valuable for the agency to move toward a more risk-based
and quality systems oriented strategy for regulating postapproval CMC
changes outside of the formal application review process? What are the
advantages and/or disadvantages?
2. Would revising Sec. 314.70 as described in this notice provide
the same level of protection to the public as the current regulatory
scheme with respect to ensuring the safety and efficacy of human drugs?
What inspectional approaches might the agency consider to evaluate
manufacturing changes while ensuring public safety?
3. Would revising Sec. 314.70 as described in this notice change
the regulatory burden on the pharmaceutical industry? If so, how would
the burden change?
4. Would reducing the prescriptiveness of Sec. 314.70 provide
manufacturers with greater regulatory flexibility? Would it encourage
manufacturers to adopt CMC-related risk management strategies? Would
there be disadvantages?
III. Registration, Agenda, and Transcript
Seating is limited and will be available on a first-come, first-
served basis. If you need special accommodations because of a
disability, please inform David J. Cummings.
Registration for Speaking Attendees: If you wish to make an oral
presentation at the meeting, you must register and submit a summary of
your presentation to David J. Cummings by January 24, 2007, via e-mail
to: David.Cummings@fda.hhs.gov. When registering, you must provide the
following information: (1) The specific topic or issue to be addressed;
(2) your name, title, company or organization, address, phone number,
and e-mail address; and (3) the approximate time requested to speak.
FDA encourages persons and groups having similar interests to
consolidate their information for presentation through a single
representative. After reviewing the requests to present, we will notify
each participant by e-mail or telephone of the amount of time allotted
and the approximate time the participant's presentation is scheduled to
begin. Presenters must send electronic copies of their presentations in
Microsoft PowerPoint, Microsoft Word, or Adobe Portable Document Format
(PDF) to David J. Cummings by noon on January 31, 2007.
Agenda and Transcript: The agenda for the public meeting will be
available February 2, 2006, on FDA's Center for Drug Evaluation and
Research (CDER) Web site at: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/meeting/OPS_20070207.htm.
After the meeting, the agenda, presentations, and
transcript will be placed on file in the Division of Dockets Management
(see ADDRESSES) under the docket number found in the heading of this
document and on CDER's Web site identified previously.
You may examine the meeting transcript Monday through Friday
between 9 a.m. and 4 p.m. in the Division of Dockets Management Public
Reading Room (see ADDRESSES) and on the Internet at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/default.htm.
You may also request a copy of the
transcript from the Freedom of Information Office (HFI-35), Food and
Drug Administration, 5600 Fishers Lane, rm. 6-30, Rockville, MD 20857,
approximately 20 working days after the meeting at a cost of 10 cents
per page or on compact disc at a cost of $14.25 each.
IV. Comments
Regardless of attendance at the meeting, interested persons may
submit to the Division of Dockets Management (see ADDRESSES) written or
electronic comments related to the questions and the focus of this
public meeting by March 7, 2007. All relevant data and information
should be submitted with the written comments. Submit a single copy of
electronic comments or two paper copies of any mailed comments, 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 received comments are available for public examination in
the Division of Dockets Management
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between 9 a.m. and 4 p.m., Monday through Friday.
Dated: December 26, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6-22588 Filed 1-4-07; 8:45 am]
BILLING CODE 4160-01-S