[Federal Register: January 17, 2006 (Volume 71, Number 10)]
[Notices]
[Page 2552-2554]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr17ja06-61]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2005D-0286]
Draft Guidance for Industry on Investigational New Drugs;
Approaches to Complying with Current Good Manufacturing Practice During
Phase 1; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of a draft guidance for industry entitled ``INDs--
Approaches to Complying with CGMP During Phase 1.'' This draft guidance
is intended to assist persons producing drug and biological products
(investigational drugs) for use during phase 1 development in complying
with relevant current good manufacturing practice (CGMP) as required by
the Federal Food, Drug, and Cosmetic Act (the FD&C Act). Controls for
producing an investigational new drug (IND) for use in a phase 1 study
are primarily aimed at ensuring subject safety. This guidance is being
issued concurrently with a direct final rule and companion proposed
rule published elsewhere in this issue of the Federal Register, which,
if finalized, will specify that the particular requirements in the
regulations need not be met for most investigational drugs manufactured
for use during phase 1 development. Instead, the agency recommends the
approaches outlined in this guidance for complying with the FD&C Act.
DATES: Submit written or electronic comments on the draft guidance by
March 20, 2006. General comments on agency guidance documents are
welcome at any time.
[[Page 2553]]
ADDRESSES: Submit written requests for single copies of the draft
guidance to the Division of Drug Information (HFD-240), Center for Drug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, or the Office of Communication, Training and
Manufacturers Assistance (HFM-40), Center for Biologics Evaluation and
Research (CBER), Food and Drug Administration, 1401 Rockville Pike,
Rockville, MD 20852-1448. Send one self-addressed adhesive label to
assist that office in processing your requests. Submit written comments
on the draft guidance to the Division of Dockets Management (HFA-305),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.
See the SUPPLEMENTARY INFORMATION section for electronic
access to the draft guidance document. The guidance may also be
obtained by mail by calling CBER at 1-800-835-4709 or 301-827-1800.
FOR FURTHER INFORMATION CONTACT: Monica Caphart, Center for Drug
Evaluation and Research (HFD-320), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-827-9047, or Christopher
Joneckis, Center for Biologics Evaluation and Research (HFM-1), 1401
Rockville Pike, Rockville, MD 20852, 301-435-5681.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``INDs--Approaches to Complying with CGMP During Phase 1.''
The FD&C Act specifies that drugs must be manufactured, processed,
packed, and held in accordance with CGMP, or they are deemed to be
adulterated. In September 1978, FDA implemented revised CGMP
regulations for drug and biological products (see parts 210 and 211 (21
CFR parts 210 and 211)). These regulations were written primarily with
commercial manufacturing in mind. Although the agency stated at the
time that the regulations applied to all types of pharmaceutical
production,\1\ we indicated in the preamble to the regulations that we
were considering proposing additional regulations governing drugs used
in investigational clinical studies. This guidance makes
recommendations for complying with CGMPs for certain phase 1 products.
---------------------------------------------------------------------------
\1\Preamble to the 1978 CGMP regulation (43 FR 45076, September
29, 1978), comment 49, ``The Commissioner finds that, as
stated in Sec. 211.1, these CGMP regulations apply to the
preparation of any drug product for administration to humans or
animals, including those still in investigational stages. It is
appropriate that the process by which a drug product is manufactured
in the development phase be well documented and controlled in order
to assure the reproducibility of the product for further testing and
for ultimate commercial production. The Commissioner is considering
proposing additional CGMP regulations specifically designed to cover
drugs in research stages.''
---------------------------------------------------------------------------
This guidance applies to investigational new human drug and
biological products (including finished dosage forms used as placebos)
intended for human use during phase 1 development. Examples of
investigational biological products covered by this guidance include
investigational recombinant and nonrecombinant therapeutic products,
vaccine products, allergenic products, in vivo diagnostics, plasma
derivative products, blood and blood components, gene therapy products,
and somatic cellular therapy products (including xenotransplantation
products) that are subject to the CGMP requirements of section
501(a)(2)(B) of the FD&C Act. The guidance applies to investigational
products whether they are produced in small- or large-scale
environments because such studies are typically designed to assess
tolerability or feasibility for further development of a specific drug
or biological product. However, if an investigational drug has already
been manufactured by an IND sponsor for use during phase 2 or phase 3
studies or has been lawfully marketed, manufacture of such a drug must
comply with the appropriate sections of part 211 for the drug to be
used in any subsequent phase 1 investigational studies, irrespective of
the trial size or duration of dosing.
This guidance does not apply to human cell or tissue products
regulated solely under section 361 of the Public Health Service Act;
clinical trials for products regulated as devices; or already approved
products that are being used during phase 1 studies (e.g., for a new
indication).
This guidance (once finalized) and the regulation it complements
(once finalized) represent the agency's effort to proceed with its
plans to formally lay out an approach to aid manufacturers in
implementing manufacturing controls that are appropriate for the stage
of development. The use of this approach recognizes that some controls
and the extent of controls needed to achieve appropriate product
quality differ not only between investigational and commercial
manufacture, but also among the various phases of clinical studies.
Consistent with the agency's CGMP for the 21st Century initiative,\2\
where applicable, manufacturers are also expected to implement controls
that reflect product and production considerations and evolving process
and product knowledge and manufacturing experience.\3\
---------------------------------------------------------------------------
\2\See http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/gmp/.
\3\We are considering issuing additional guidance and/or
regulations to clarify the agency's expectations with regard to
fulfilling the CGMP requirements when producing investigational
drugs for phase 2 and phase 3 clinical studies.
---------------------------------------------------------------------------
The draft guidance describes FDA's current thinking regarding
controls for special production situations (e.g., a laboratory setting,
exploratory studies, multiproduct and multibatch testing) and specific
product types (e.g., biological/biotechnology products, aseptically
processed products) of IND products manufactured for use during phase 1
clinical trials as described in the scope section of the guidance. As
the new rule will specify if finalized, the particular requirements in
part 211 need not be met for most exploratory products manufactured for
use during phase 1 clinical trials.
When finalized, this guidance will replace the 1991 ``Guideline on
the Preparation of Investigational New Drug Products (Human and
Animal)'' for the production of IND products for phase 1 clinical
trials described in the scope section of the guidance. Phase 2 and 3
production will continue to be subject to those portions of parts 210
and 211 that are applicable.
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 how to
comply with CGMP during certain phase 1 clinical studies. 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. Paperwork Reduction Act of 1995
This draft guidance refers to collections of information that have
been approved by the Office of Management and Budget (OMB) under the
Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). OMB approved the
collection of information under OMB control number 0910-0139.
III. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this document.
Submit a single copy of electronic
[[Page 2554]]
comments or two paper copies of any mailed comments, except that
individuals may submit one paper 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.
IV. Electronic Access
Persons with access to the Internet may obtain the document at
http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/index.htm, http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cber/guidelines.htm, or http://www.fda.gov/ohrms/dockets/default.htm.
ets/default.htm.
Dated: January 9, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 06-352 Filed 1-12-06; 8:45 am]
BILLING CODE 4160-01-S