[Federal Register Volume 72, Number 210 (Wednesday, October 31, 2007)]
[Notices]
[Pages 61656-61657]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-21403]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004D-0484]


Guidance for Industry on the Role of Human Immunodeficiency Virus 
Resistance Testing in Antiretroviral Drug Development; 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 ``Role of HIV 
Resistance Testing in Antiretroviral Drug Development.'' This guidance 
is intended to assist sponsors in the clinical development of drugs for 
the treatment of human immunodeficiency virus (HIV) infection. 
Specifically, this guidance addresses the agency's current thinking 
regarding the role of HIV resistance testing during antiretroviral drug 
development and postmarketing. This guidance discusses important 
nonclinical studies that are recommended before the initiation of phase 
1 clinical studies in HIV-infected patients. In addition, this guidance 
addresses the use of resistance testing in clinical phases of drug 
development and recommends the type of information that should be 
collected and the types of analyses that should be conducted to 
characterize an antiretroviral's resistance profile. This guidance 
finalizes the draft guidance published on November 29, 2004.

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://www.fda.gov/dockets/ecomments or http://www.regulations.gov. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Jeffrey Murray, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, rm. 6360, Silver Spring, MD 20993-0002, 301-
796-1500, or
    Kimberly Struble, Center for Drug Evaluation and Research, Food and 
Drug Administration, 10903 New Hampshire Ave., Bldg. 22, rm. 6374, 
Silver Spring, MD 20993-0002, 301-796-1500.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Role of HIV Resistance Testing in Antiretroviral Drug 
Development.'' This guidance is intended to assist sponsors in the 
clinical development of drugs for the treatment of HIV infection. 
Specifically, this guidance addresses the agency's current thinking 
regarding the role of HIV resistance testing during antiretroviral drug 
development and postmarketing. This guidance discusses the nonclinical 
studies (mechanism of action, antiviral activity in vitro, the effects 
of serum protein binding on antiviral activity, cytotoxicity and 
therapeutic index, and in vitro combination activity) that should be 
completed before the initiation of phase 1 clinical studies in HIV-
infected patients. In addition, this guidance

[[Page 61657]]

addresses the use of resistance testing in clinical phases of drug 
development and recommends the type of information that should be 
collected and the types of analyses that should be conducted to 
characterize an antiretroviral's resistance profile. This guidance also 
is intended to serve as a focus for continued discussions among the 
Division of Antiviral Products, pharmaceutical sponsors, the academic 
community, and the public.
    This guidance is based on a 2-day session of the Antiviral Drug 
Product Advisory Committee convened on November 2 and 3, 1999, to 
address issues relating to HIV resistance testing, the division's 
experience with reviewing resistance data for antiretroviral drugs, and 
input from pharmaceutical sponsors and the HIV community.
    This guidance has been updated to address public comments on the 
draft version. The following significant changes were made to the 
guidance: (1) The inclusion of more details and clarification on the 
recommendations about the amount and type of nonclinical studies that 
should be conducted before phase 1 clinical studies, (2) the inclusion 
of more details and clarification regarding data collection and types 
of analyses for treatment-na[iuml]ve and treatment-experienced 
patients, (3) the inclusion of additional details regarding exposure-
response analyses, and (4) updated guidance for submitting HIV 
resistance data.
    The guidance reviews the role of resistance testing in initial 
activity and dose-finding studies, for study enrollment criteria, and 
background regimen selection. The guidance also reviews the use of 
resistance data to establish an indication. This guidance includes an 
appendix that provides recommendations on how to submit HIV resistance 
data to FDA.
    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 the role of HIV resistance testing in 
antiretroviral drug development. 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 guidance refers to previously approved collections of 
information found in FDA regulations. These collections of information 
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 
collections of information in 21 CFR part 312 have been approved under 
OMB control number 0910-0014.

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 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. Received comments may be seen 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://www.fda.gov/ohrms/dockets/default.htm.

    Dated: October 24, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-21403 Filed 10-30-07; 8:45 am]
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