FDA Notifications

FDA grants tentative approval of generic efavirenz tablets

On Dec. 20, 2007, the FDA granted tentative approval for a generic formulation of efavirenz tablets, 600 mg, manufactured by Emcure Pharmaceuticals of Pune, India The application was reviewed under the expedited review provisions of the President's Emergency Plan for AIDS Relief (PEPFAR).

As with all generic applications, the 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.

However, although tentatively approved generic products meet required standards, they cannot yet be fully approved and sold in the United States because of existing patents and/or exclusivity rights. But the tentative approval does make the product eligible for consideration for purchase, under the PEPFAR program, for use in nations where PEPFAR is active.

This product is a generic formulation of Sustiva tablets, 600 mg, made by Bristol Myers Squibb Co., which is subject to existing patents, as listed in the agency's publication titled, "Approved Drug Products with Therapeutic Equivalence Evaluations," also known as the "Orange Book."

Efavirenz is a Nonnucleoside Reverse Transcriptase Inhibitors (NNRTI) indicated for treatment of HIV infection in combination with other antiretroviral agents.

Fosamprenavir label is updated

The fosamprenavir (Lexiva) label was recently updated to include new drug-drug interaction information regarding phenytoin (an anticonvulsant) and paroxetine (an antidepressant).

Details of the newly added information are contained at the following Web site address: www.fda.gov.

Final rule is out on OTC vaginal contraceptives and spermicides

The FDA issued a final rule on December 18, 2007, requiring that manufacturers of over-the-counter (OTC), stand-alone vaginal contraceptive and spermicidal products containing the chemical ingredient nonoxynol 9 (N9) include a warning stating that the chemical N9 does not provide protection against infection from HIV (the virus that causes AIDS) or other sexually transmitted diseases (STDs).

Stand-alone spermicides include gels, foams, films, or inserts containing N9 that are used by themselves for contraception. Consumers can protect themselves from the transmission of STDs and HIV by practicing abstinence, being in a monogamous relationship where neither partner is infected, and using condoms consistently and correctly.

The FDA is issuing the rule in an effort to correct misconceptions that N9 protects against sexually transmitted diseases, including HIV infection.

Nonoxynol 9 is approved as a vaginal contraceptive that works by damaging the cell membrane of sperm. It has been shown in laboratory studies to damage the cell walls of certain organisms that cause STDs and to be active against some STD-causing bacteria and viruses. Over the years, many consumers have come to believe that N-9 could reduce the potential for transmission of HIV and other STDs. The FDA believes that the membrane-damaging effect can harm the cell lining of the vagina, cervix and rectum, thereby increasing the risk of HIV and STD transmission.

The FDA is requiring that the labels warn consumers that the chemical N9 in stand-alone vaginal contraceptives and spermicides can irritate the vagina and rectum, which may increase the risk of contracting HIV/AIDS from an infected partner.

In January, 2003, the FDA proposed new warning statements and other labeling information for these products after results from a major clinical study in Africa and Thailand showed that women using a contraceptive gel product containing N9 were not protected against HIV and other STDs and were, in fact, at higher risk for HIV infection than women using a placebo gel. Because these and other studies have shown that use of products containing N9 cause vaginal and rectal irritation that can heighten the chance of becoming infected with HIV from an infected partner, the FDA believes the warning will empower consumers to make more informed decisions about the use of these products and better protect public health.

This rule is being finalized following a public comment period and a thorough analysis of information and views from consumers, health care providers, academicians, and industry. The FDA is requiring that labeling of OTC vaginal contraceptive/spermicidal products containing N9 bear the following warnings:

- For vaginal use only

- Not for rectal (anal) use

- Sexually transmitted diseases (STDs) alert: This product does not protect against HIV/AIDS or other STDs and may increase the risk of getting HIV from an infected partner

- Do not use if you or your sex partner has HIV/AIDS. If you do not know if you or your sex partner is infected, choose another form of birth control.

- When using this product, you may get vaginal irritation (burning, itching, or a rash). Stop use and ask a doctor if you or your partner get burning, itching, a rash, or other irritation of the vagina or penis.

Other information in the new labeling includes:

- Studies have raised safety concerns that products containing the spermicide nonoxynol 9 can irritate the vagina and rectum. Sometimes this irritation has no symptoms. This irritation may increase the risk of getting HIV/AIDS from an infected partner.

- You can use nonoxynol 9 for birth control with or without a diaphragm or condom if you have sex with only one partner who is not infected with HIV and who has no other sexual partners or HIV risk factors

- When used correctly every time you have sex, latex condoms greatly reduce, but do not eliminate the risk of catching or spreading HIV, the virus that causes AIDS.

Use a latex condom without nonoxynol 9 if you or your sex partner has HIV/AIDS, multiple sex partners, or other HIV risk factors

- Ask a health professional if you have questions about your best birth control and STD prevention methods

The FDA is issuing the final rule to provide a clear, consistent message that N9 is not effective in preventing HIV transmission, and that N9 may actually facilitate transmission of the disease for those who are at risk for HIV/AIDS. The final rule is consistent with FDA's draft guidance for N9 use with condoms.

The full text of the final rule is available at www.fda.gov

FDA proposes to revise/update regulations regarding blood and plasma

The FDA proposes to revise and update the regulations applicable to blood and blood components, including Source Plasma and Source Leukocytes, to add donor requirements that are consistent with current practices in the blood industry, and to more closely align the regulations with current FDA recommendations. The FDA is taking this action to help ensure the safety of the national blood supply and to help protect donor health by requiring establishments to evaluate donors for factors that may adversely affect the safety, purity, and potency of blood and blood components, or the health of a donor during the donation process.

Through the years, the FDA has issued a number of guidance documents containing recommendations intended to assure a safe, pure, and potent blood supply. The Notice of Proposed Rulemaking discusses the recommendations contained in current guidance that fall under the proposed regulation, including donor eligibility and screening for HIV and certain other transfusion-transmitted infections. The FDA believe the proposed rule will more explicitly describe donor eligibility standards and will clarify the relationship between the regulations and the applicable recommendations.

The proposed rule, among other things, provides for the establishment of minimum criteria for the assessment of donor eligibility and the suitability of the donation of blood and blood components. The rule is expected to have a minor net impact on blood establishments because it is already usual and customary business practice in the blood industry to assess donors for eligibility and donations for suitability. The FDA believes the primary impact of the rule will be the one-time review of current SOPs that the proposed rule would require each blood collecting establishment to conduct.

Written or electronic comments on the proposed rule, identified by Docket No. 2006N- 0221, may be submitted to the agency until February 6, 2008 through any of the following methods:

Electronic Submissions: Submit electronic comments in the following ways:

- Federal eRulemaking Portal: http://www.regulations.gov/search/index.jsp. Follow the instructions for submitting comments.

- Agency Web site: http://frwebgate.access.gpo.gov. Follow the instructions for submitting comments on the agency Web site.

Written Submissions: Submit written submissions in the following ways: FAX: 301-827-6870. Mail/Hand delivery/Courier [For paper, disk, or CD-ROM submissions]: Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.