[Federal Register: July 22, 2005 (Volume 70, Number 140)]
[Notices]               
[Page 42346]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr22jy05-63]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2002D-0492] (formerly Docket No. 02D-0492)

 
Guidance for Industry on Estimating the Maximum Safe Starting 
Dose in Initial 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 guidance for industry entitled ``Estimating the 
Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics 
in Adult Healthy Volunteers.'' This guidance provides a description and 
basis for a process by which to select a maximum recommended starting 
dose (MRSD) for a first-in-human clinical trial of a therapeutic in 
adult healthy volunteers.

DATES: Submit written or electronic comments on agency guidances at any 
time.

ADDRESSES: Submit written requests for single copies of this 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 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 guidance document.

FOR FURTHER INFORMATION CONTACT: Lois M. Freed, Center for Drug 
Evaluation and Research (HFD-120), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-594-2647.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Estimating the Maximum Safe Starting Dose in Initial 
Clinical Trials for Therapeutics in Adult Healthy Volunteers.'' This 
guidance provides a description and basis for a process by which to 
select an MRSD for a first-in-human clinical trial of a new molecular 
entity in adult healthy volunteers. In the Federal Register of January 
16, 2003 (68 FR 2340), FDA published a notice making available a draft 
guidance entitled ``Estimating the Safe Starting Dose in Clinical 
Trials for Therapeutics in Adult Healthy Volunteers.'' The notice gave 
interested persons an opportunity to submit comments. As a result of 
the comments, certain sections of this guidance were reworded to 
improve clarity. The guidance outlines a recommended standardized 
approach (including common conversion factors for calculating human 
equivalent doses) and vocabulary for selecting an MRSD based on animal 
data, and discusses factors to be considered in determining reasonable 
safety margins. This approach is applicable to a first-in-human trial 
of a new drug or biological therapeutic, regardless of intended 
clinical use. The guidance also discusses alternative approaches and 
provides some examples of circumstances under which alternative 
approaches for selection of an MRSD should be considered. Dose 
escalation is not addressed.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
agency's current thinking on estimating the 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 Division of Dockets Management 
(see ADDRESSES) written or electronic comments on the guidance at any 
time. 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 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.

III. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=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: July 14, 2005.

Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-14456 Filed 7-21-05; 8:45 am]

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