[Federal Register Volume 71, Number 10 (Tuesday, January 17, 2006)]
[Notices]
[Pages 2552-2554]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 06-352]


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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Draft Guidance for Industry on Investigational New Drugs; 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.

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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availability of a draft guidance for industry entitled ``INDs--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 This draft guidance 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DATES: Submit written or electronic comments on the draft guidance by 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.

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ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information (HFD-240), Center for Drug 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on the draft guidance to the Division of Dockets Management (HFA-305), 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://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.
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    \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.''
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    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\
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    \2\See 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.
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    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

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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://www.fda.gov/cder/guidance/index.htm, http://www.fda.gov/cber/guidelines.htm, or http://www.fda.gov/ohrms/dockets/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