[Federal Register Volume 71, Number 201 (Wednesday, October 18, 2006)]
[Notices]
[Pages 61483-61484]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-17324]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004D-0228]


Guidance for Industry on Fixed Dose Combinations, Co-Packaged 
Drug Products, and Single-Entity Versions of Previously Approved 
Antiretrovirals for the Treatment of HIV; 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 ``Fixed Dose 
Combinations, Co-Packaged Drug Products, and Single-Entity Versions of 
Previously Approved Antiretrovirals for the Treatment of HIV.'' The 
guidance is intended to encourage sponsors to submit to FDA 
applications for fixed dose combination (FDC), co-packaged, and single-
entity versions of antiretroviral drugs for the treatment of human 
immunodeficiency virus (HIV). The availability of a wide range of safe 
and effective antiretroviral products may help facilitate a wider 
distribution of anti-HIV drugs to better meet the demands of the global 
HIV/AIDS pandemic.

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

[[Page 61484]]


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. 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.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled, ``Fixed Dose Combinations, Co-Packaged Drug Products, and 
Single-Entity Versions of Previously Approved Antiretrovirals for the 
Treatment of HIV.'' This guidance is intended to encourage the 
development of various configurations of previously approved 
antiretroviral products for the treatment of HIV. The guidance 
addresses the agency's current thinking regarding the types of 
information that should be provided in an application seeking approval 
for FDC, co-packaged, or single-entity products for the treatment of 
HIV.
    The draft version of this guidance, entitled ``Fixed Dose 
Combination and Co-Packaged Drug Products for Treatment of HIV,'' was 
issued in May 2004. The guidance has been updated to address public 
comments to the draft version. Significant changes to the draft are as 
follows: (1) The inclusion of single-entity versions, in addition to 
combination products, in the expedited FDA review pathway; (2) the 
addition of tables that supply references supporting the clinical 
efficacy and safety of antiretroviral combinations; and (3) 
clarification on the amount and type of data that should be submitted 
in a drug application to support approval or tentative approval.
    Combination therapy is essential for the treatment of HIV/AIDS. At 
least three active drugs, usually from two different classes, are 
required to suppress the virus, allow recovery of the immune system, 
and reduce the emergence of HIV resistance. In the United States and 
developing countries, the availability of a wide range of 
antiretroviral drug products, including simplified HIV regimens in the 
form of co-packaged drugs (such as blister packs) or FDCs may 
facilitate distribution of antiretroviral therapies and improve patient 
adherence to the regimens.
    Although there are more than 20 unique antiretroviral drugs 
approved in the United States, only a few are approved for use as FDC 
products, and none are approved as co-packaged products. Some 
antiretrovirals should not be combined because of overlapping 
toxicities and potential viral antagonism. Other antiretrovirals should 
not be used in pregnant women and other special populations. Therefore, 
it is important that possible combinations of these products be 
evaluated for safety and efficacy in the populations that may have need 
of them.
    Recently, newer FDCs and single-entity products that have not been 
approved by FDA have received attention, and some are being promoted 
for use in resource poor nations where HIV/AIDS has reached epidemic 
proportions. These products may offer cost advantages or allow 
simplified dosing. However, the safety, efficacy, and quality of many 
of these products have not been evaluated by FDA. Products whose 
safety, efficacy, and quality do not conform to expected standards may 
pose a threat to individual patients by increasing the chances of 
substandard performance, which may lead not only to treatment failure, 
but also to the development and spread of resistant virus.
    FDA is prepared to move swiftly to evaluate such products when 
applications for them are submitted for approval. This guidance 
clarifies what regulatory requirements would be applied to such 
applications, what issues might be of concern, and how these should be 
addressed. Different considerations apply depending on whether a 
sponsor owns or has a right of reference to all of the data required to 
support an application or whether a sponsor plans to rely on literature 
or FDA's findings of safety and effectiveness for an approved drug. 
Where appropriate, this guidance addresses the issues associated with 
these different situations.
    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 FDC, co-packaged, and single-entity 
products for treating HIV infection. 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 regarding this document. 
Submit a single comment 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.

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: October 11, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6-17324 Filed 10-17-06; 8:45 am]
BILLING CODE 4160-01-S