[Federal Register Volume 68, Number 11 (Thursday, January 16, 2003)]
[Notices]
[Pages 2340-2341]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-906]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 02D-0492]


Draft Guidance for Industry and Reviewers on Estimating the Safe 
Starting Dose in Clinical Trials for Therapeutics in Adult Healthy 
Volunteers; 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availability of a draft guidance for industry and reviewers entitled 
``Estimating the Safe Starting Dose in Clinical Trials for Therapeutics 
in Adult Healthy Volunteers.'' This draft guidance outlines a common 
process (algorithm) and terminology for deriving a maximum recommended 
starting dose for ``first in human'' clinical trials of new molecular 
entities in adult healthy volunteers. Described in the guidance is a 
method for using nonclinical data to select a maximum starting dose in 
adult humans that is not expected to result in significant toxicity. 
The goal is to ensure the safety of adult human volunteers in initial 
clinical trials.

DATES: Submit written or electronic comments on the draft guidance by 
March 17, 2003. General comments on agency guidance documents are 
welcome at any time.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information (HFD-240), Center for Drug 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. Send two self-addressed adhesive labels to 
assist that office in processing your requests. Submit written comments 
on the draft guidance to the Dockets Management Branch (HFA-305), Food 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access to the draft guidance document.

[[Page 2341]]


FOR FURTHER INFORMATION CONTACT: Robert E. Osterberg, Center for Drug 
Evaluation and Research (HFD-24), Food and Drug Administration, 1451 
Rockville Pike, Rockville, MD 20852, 301-594-5482 or M. David Green, 
Center for Biologics Evaluation and Research (HFM-579), Food and Drug 
Administration, 1401 Rockville Pike, Rockville, MD 20852, 301-827-5349.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
and reviewers entitled ``Estimating the Safe Starting Dose in Clinical 
Trials for Therapeutics in Adult Healthy Volunteers.'' When selecting 
the starting dose in an initial clinical trial for a new molecular 
entity (NME), one can only rely on the safety data generated in 
nonclinical studies since, by definition, there are no human data. The 
draft guidance describes a method by which a starting dose may be 
selected for an initial clinical trial that is not expected to result 
in significant toxicity, but that will allow reasonably rapid 
attainment of phase I trial objectives (e.g., assessment of the NME's 
tolerability, pharmacodynamic and/or pharmacokinetic profile). The 
draft guidance establishes a consistent terminology for discussing the 
starting dose and a strategy for selecting a maximum recommended safe 
starting dose based on no-observed-adverse-effect levels in animals. 
Common conversion factors for deriving human equivalent doses from 
animal data are provided, and factors to be considered in determining 
reasonable safety margins are discussed in detail. The draft guidance 
also addresses the use of the nonclinical pharmacologically active dose 
and systemic exposure data in selection of a maximum recommended 
clinical starting dose. Comments on dose escalation are outside the 
scope of this draft document.
    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 estimating a 
maximum safe starting dose in initial clinical trials for therapeutics 
in adult healthy volunteers. 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. Comments

    Interested persons may submit to the Dockets Management Branch (see 
ADDRESSES) written or electronic comments on the draft guidance. Two 
copies of mailed comments are to be submitted, 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 draft 
guidance and received comments are available for public examination in 
the Dockets Management Branch between 9 a.m. and 4 p.m., Monday through 
Friday.

III. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http://www.fda.gov/cder/guidance/index.htm or http://www.fda.gov/ohrms/dockets/default.htm.

    Dated: January 8, 2003.
Margaret M. Dotzel,
Assistant Commissioner for Policy.
[FR Doc. 03-906 Filed 1-15-03; 8:45 am]
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