[Federal Register: April 14, 2005 (Volume 70, Number 71)]
[Notices]               
[Page 19764-19765]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr14ap05-50]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2005D-0122]

 
Draft Guidance for Industry on Exploratory Investigational New 
Drugs Studies; 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availability of a draft guidance for industry entitled ``Exploratory 
IND Studies.'' This draft guidance clarifies what preclinical and 
clinical issues (including chemistry, manufacturing, and controls 
issues) should be considered when planning exploratory studies in 
humans, including studies of closely related drugs or biologics, under 
an investigational new drug (IND) application. This draft guidance 
emphasizes the concept that limited investigations in humans can be 
initiated with more limited preclinical support because such studies 
present fewer potential risks than do traditional phase 1 studies that 
look for dose-limiting toxicities.

DATES: Submit written or electronic comments on the draft guidance by 
July 13, 2005. General comments on agency guidance documents are 
welcome at any time.

ADDRESSES: Submit written requests for single copies of the 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. 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draft guidance to the Division of Dockets Management (HFA-305), Food 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access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: David Jacobson-Kram, Center for Drug 
Evaluation and Research (HFD-24), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-443-5346.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Exploratory IND Studies.'' In its March 2004 Critical Path 
Report, the agency explained that to reduce the time and resources 
expended during early drug development on candidates that are unlikely 
to succeed, tools are needed to allow developers to distinguish earlier 
in the process those candidates that hold promise from those that do 
not. This guidance describes some exploratory approaches that will 
protect human subjects while providing early information about 
candidate performance in humans.
    Exploratory IND studies have a number of different goals. In some 
cases, an exploratory study can help developers gain an understanding 
of the relationship between a specific mechanism of action and the 
treatment of a disease. In other cases, a study can provide important 
information on pharmacokinetics, including, for example, 
biodistribution of a candidate drug. Whatever the goal of the study, 
exploratory IND studies can help sponsors identify, early in the 
process, promising candidates for continued development.
    Existing regulations allow a great deal of flexibility in terms of 
the amount of data that need to be submitted in an IND application, 
depending on the goals of an investigation, the specific human testing 
being proposed, and the expected risks. Nevertheless, sponsors have not 
always taken advantage of that flexibility and limited, early phase 1 
studies, such as those described in this document, are often supported 
by a more extensive preclinical database than is needed. In many cases, 
a more extensive workup is done because sponsors intend to move 
immediately into a more traditional phase 1 trial if the screening 
results are favorable. Because exploratory studies will typically 
involve administering either subtherapeutic doses of a product, or 
doses expected to produce a pharmacological, but not a toxic effect, 
the potential risk to human subjects is less than for a traditional 
phase 1 study that, for example, seeks to establish a maximally 
tolerated dose.
    This guidance applies to exploratory studies (i.e., early phase 1 
clinical studies), involving investigational new drug and biological 
products, that assess feasibility for further development of a drug or 
biological product. For the purposes of this guidance the phrase 
``exploratory study'' is intended to describe clinical trials that 
occur very early in phase 1, involve very limited human exposure, and 
often have no therapeutic intent.
    Typically, these exploratory studies are conducted prior to the 
traditional

[[Page 19765]]

dose evaluation, safety, and tolerance studies that ordinarily initiate 
a clinical drug development program. Thus, FDA believes that, 
typically, the duration of dosing would be limited (e.g., 7 days). The 
agency is, however, interested in soliciting comment from the public on 
the appropriate duration of dosing for such exploratory studies.
    The amount and type of preclinical information necessary to support 
an exploratory study will depend on the planned nature and extent of 
human exposure relative to the toxicity (or lack thereof) at the 
planned dose. Thus, this guidance emphasizes the concept that limited 
investigations in humans can be initiated with more limited preclinical 
support because such studies present fewer potential risks than do 
traditional phase 1 studies that look for dose-limiting toxicities. The 
studies discussed here ordinarily do not have therapeutic intent. They 
are designed to evaluate whether a particular candidate should be 
entered into a drug development program.
    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 exploratory 
IND 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 contains information collection provisions that 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The 
collection of information in this guidance has been approved under OMB 
control number 0910-0014 and expires on January 31, 2006.

III. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments on the draft guidance. 
Submit a single copy of electronic 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 
either http: //www.fda.gov/cder/guidance/index.htm or http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/default.htm
.


    Dated: April 8, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-7485 Filed 4-13-05; 8:45 am]

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