FDA Notifications

FDA approves half-strength Kaletra

On Nov. 9, 2007, the FDA approved a new half-strength Kaletra tablet formulation. Each film-coated tablet contains 100 mg lopinavir and 25 mg ritonavir. The major changes to the label include clear instructions regarding the importance of accurate calculation of the dose of Kaletra to minimize the risk for medication errors and overdose or under dose, and the addition of tablet dosing to section 2.2 Pediatric Patients, as described in the pdf attachment.

Kaletra is a combination protease inhibitor product containing lopinavir and ritonavir, manufactured by Abbott Laboratories. The original formulation was approved on September 15, 2000.

FDA's final guidance on HIV resistance testing

The FDA is publishing its final "Guidance for Industry on the Role of HIV Resistance Testing in Antiretroviral Drug Development."

This final guidance discusses the nonclinical studies (mechanism of action; antiviral activity in vitro; cytotoxicity/therapeutic index; and the effects of serum protein binding on antiviral activity) the agency recommends be completed prior to the initiation of phase I clinical studies in HIV-infected patients. In addition, the guidance addresses the use of resistance testing in the 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.

The guidance also discusses the role of resistance testing in initial activity and dose-finding, for study enrollment criteria, for background regimen selection, and to establish an indication.

The guidance represents the agency's current thinking on the role of HIV resistance testing in antiretroviral drug development. As with all FDA guidance for industry, 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.

A copy of the final guidance document is attached. You may find this and other Guidance for Industry on the FDA web site at www.fda.gov

FDA's tentative approval for generic Tenofovir

On Nov. 30, 2007, FDA granted tentative approval for a generic version of Tenofovir Disoproxil Fumarate Tablets, 300 mg, manufactured by Matrix Laboratories Limited, of Hyderabad, India. The application was reviewed under the expedited review provisions of the President's Emergency Plan for AIDS Relief (PEPFAR).

"Tentative Approval" means that FDA has concluded that a drug product has met all required quality, safety, and efficacy standards, even though it is not yet eligible to be marketed in the United States because of existing patents and/or exclusivity rights. However, this tentative approval does make the product eligible for consideration for purchase under the PEPFAR program.

This is a generic version of Viread Tablets, 300 mg, manufactured by Gilead Sciences, Inc,, which is subject to existing patent protection.

Effective patent dates can be found in the agency's publication titled Approved Drug Products with Therapeutic Equivalence Evaluations, also known as the "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 prior to granting approval or tentative approval to these applications to evaluate the ability of the manufacturer to produce a quality product and to assess the quality of the bioequivalence data supporting the application.

Tenofovir is a nucleoside reverse transcriptase inhibitor (NRTI) indicated for treatment of HIV infection in adults and adolescents in combination with other antiretroviral agents.

FDA approval for generic lamivudine/zidovudine

On Nov. 29, 2007, FDA granted tentative approval for a generic formulation of combination lamivudine/zidovudine tablets, 150 mg/300 mg, manufactured by Matrix Laboratories, Inc. of Hyderabad, India, under expedited review provisions developed for the President's Emergency Plan for AIDS Relief (PEPFAR).

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

This is a generic formulation of Combivir Tablets, 150 mg/300 mg, marketed by GlaxoSmithKline, which is subject to existing patent and pediatric exclusivity protections.

Effective patent dates and additional marketing exclusivities can be found in the agency's publication titled Approved Drug Products with Therapeutic Equivalence Evaluations, also known as the "Orange Book."

Lamivudine and zidovudine are both Nucleoside Reverse Transcriptase Inhibitors (NRTI) indicated for used in combination with other antiretroviral agents in the treatment of HIV infection.