Problems with bioequivalence are FDA's main reason for rejecting FDC applications, and formulation issues can be difficult to solve. Last December, for example, Gilead Sciences and BMS announced plans to develop an FDC combining Gilead's Truvada (emtricitabine/tenofovir) and BMS' Sustiva (efavirenz) to create a more potent once-daily AIDS treatment. But several test versions failed to achieve bioequivalence to the drugs used separately. Gilead plans to test three more formulations in hope of submitting an application in 2006.

Although FDA approval makes drugs eligible for PEPFAR, manufacturers still have to register the products in each recipient country before they can be distributed to patients. Ironically, African governments also want FDA-approved drugs included on WHO's prequalification list so that they can use the same drugs for all programs. FDA and WHO officials recently signed an agreement that will permit FDA to provide confidential data to WHO to facilitate prequalification.

Managing the Supply Chain

To prevent such problems, donors and health programs seek to establish secure distribution and warehousing systems to manage the fast-expanding quantities of ARVs going to developing countries. PEPFAR and the US Agency for International Development (USAID) are currently designing their own secure supply-chain management system (SCMS) for the program's 15 focus countries. USAID is negotiating a contract, which could amount to $7 billion over five years, to establish a "one-stop shopping point" for medical supplies, which also will negotiate prices, prevent theft and diversion, and verify quality.

Many observers consider the PEPFAR/USAID initiative redundant with similar programs already under development. PEPFAR officials say that local governments and third-party donors will have the option of using their own systems instead of SCMS, but organizations receiving PEPFAR funds may well feel pressure to adopt the US program.

Promoting Innovation

While the immediate goal of AIDS programs is to provide treatment for millions of infected patients, a broader aim is to encourage development of new therapies to meet future needs. The good news is that efforts to deal with current crises do not seem to be curbing innovation. In July, Boehringer Ingelheim announced FDA approval of its new protease inhibitor Aptivus (tipranavir). Massachusetts-based Panacos Pharmaceuticals unveiled early clinical trial results in August indicating high efficacy from a new maturation-inhibitor antiretroviral made from the bark of the European plane tree. New studies are examining whether ARVs may be effective at preventing HIV infection in the first place.

Research also is generating hope for new treatments for malaria and TB. Last year, the Institute of Medicine issued a report calling for major global investment in new artemisinin-based combination therapies (ACTs) due to the drug's positive results. Promising treatments against tuberculosis are being tested, which is important in the United States as drug-resistant TB cases have emerged in California. The resulting new drugs may prevent disease spread and help cure already stricken patients.

Jill Wechsler is Pharm Exec's Washington correspondent. She can be reached at jwechsler@ advanstar.com