FDA Notifications

FDA draft guidance on Hepatitis C/HIV coinfection

The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled "Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Agents for Treatment," which includes coinfection with HIV.

At present, there are a large number of drugs for the treatment of chronic hepatitis C (CHC) in active development. The purpose of this guidance is to assist sponsors in all phases of development of direct-acting antiviral agents (DAAs), defined as agents that interfere with specific steps in the hepatitis C virus (HCV) replication cycle. The guidance outlines the types of nonclinical studies and clinical trials recommended throughout the drug development process, such as early phases of clinical development, phase 3 protocol designs, and endpoints for the treatment of CHC to support approval of treatments for CHC, including patients with compensated and decompensated cirrhosis and those coinfected with HIV. The guidance also addresses pre-approval access in the form of treatment investigational new drug applications (INDs) and intermediate-sized safety protocols (collectively known as expanded access).

Important issues addressed in this guidance include: drug development methods to reduce the emergence of drug resistance, types of trial designs to assess optimal dose and treatment duration, combination therapy with multiple investigational drugs, recommendations on development of drugs to meet unmet medical needs, and use of treatment INDs or other smaller safety protocols to provide early access of multiple DAAs for patients at risk of imminent progression of liver disease.

The draft guidance, when finalized, will represent the agency's current thinking on developing DAAs for treatment of CHC virus infection.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.

The draft guidance is available on the FDA web site at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM225333.pdf.

Although comments are accepted for any guidance at any time, to ensure that the agency considers your comment on this draft guidance before it begins work on the final version of the guidance, please submit written or electronic comments on the draft guidance by November 15, 2010, and include the docket number, FDA-2010-D-0462, in any comment you submit.

You may 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

You may also submit electronic comments at http://www.regulations.gov/search/Regs/home.html#submitComment?R=0900006480b4e9b3.

Fixed combination tablet approved

On Sept. 10, 2010, the FDA granted tentative approval for a fixed dose combination formulation of lamivudine, nevirapine, and stavudine tablets, 150 mg/200 mg/30 mg indicated for use alone or in combination with other antiretrovirals for the treatment of HIV-1 infection. This fixed-dose combination is manufactured by Hetero Drugs Limited of Hyberdad, India.

The FDA's tentative approval means that although a product meets all of the safety, efficacy, and manufacturing quality standards required for marketing in the U.S., existing patents and/or proprietary issues currently prevent marketing of the product in the United States. Tentative approval, however, does qualify the product for consideration for purchase under the President's Emergency Plan for AIDS Relief, or PEPFAR program.

This Fixed Dose Combination product was reviewed for PEPFAR under the FDA guidance titled Fixed Dose Combinations, Co-Packaged Drug Products, and Single-Entity Versions of Previously approved Antiretrovirals for the Treatment of HIV developed to clarify what regulatory requirements apply to such applications, what issues might be of concern, and how these issues should be addressed. The guidance is intended to encourage sponsors to submit applications for combination and co-packaged products, and to facilitate submission of such applications to FDA.

A complete list of all Approved and Tentatively Approved Antiretrovirals in Association with the President's Emergency Plan is available on the FDA web site.

FDA approves generic abacavir

On Sept. 29, 2010, the FDA granted tentative approval for a generic formulation of abacavir sulfate tablets, 300 mg, indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults.

This generic formulation is manufactured by Hetero Drugs Limited, of Hyberdad, India. The application was reviewed under expedited review provisions for the President's Emergency Plan for AIDS Relief (PEPFAR).

Current patent information about approved drugs can be found in FDA's Orange Book.

As with all generic applications, FDA conducts an on-site inspection of each manufacturing facility, and of the facilities performing the bioequivalence studies, to evaluate the ability of the manufacturer to produce a quality product and to assess the quality of the bioequivalence data supporting the application prior to granting approval or tentative approval to these applications.

You can find a complete list of all Approved and Tentatively Approved Antiretrovirals in Association with the President's Emergency Plan on the FDA web site.

This formulation of abacavir sulfate, a Nucleoside Reverse Transcriptase Inhibitors (NRTI) is a generic version of Ziagen® Tablets, 300 mg, a product of VIIV Healthcare Co.