The whole world wants more antiretroviral medicines (ARVs), particularly fixed-dose combination drugs (FDCs), which are easier
for sick people in developing nations to use correctly. US, European, and international organizations are pledging billions
of dollars to treat five million AIDS patients over the next few years, and the President's Emergency Plan for AIDS Relief
(PEPFAR) plans to spend $15 billion over five years to treat two million individuals—huge leaps from the mere thousands now
receiving ARVs in developing nations. US initiatives have drawn considerable attention, along with criticism, about reinventing
the wheel and wasting resources on pricey branded medicines.
A crucial first step is to ramp up the availability of treatment services and medical supplies. That will be a challenge,
but it also offers pharmaceutical manufacturers a great opportunity to demonstrate their ability to provide affordable, effective
treatments. Generic drug makers are already playing an important role in these efforts—a role they are poised to expand if
innovator firms shy away. Meanwhile, the industry has to formulate effective combination products, meet worldwide regulatory
standards, and obtain ingredients—an assignment that will stress pharma on all sides. Bristol-Myers Squibb, for example, reported
in March that it might not meet demand for Zerit (stavudine) and Sustiva (efavirenz).
Supply problems were aggravated this past year when the World Health Organization (WHO) delisted several important generic
FDCs from the agency's prequalification program for drugs to treat AIDS, malaria, and tuberculosis. The issue: discrepancies
in bioequivalence (BE) data. WHO, which began inspecting BE contract labs in 2004, discovered that the facilities did not
meet international standards. What is more, some manufacturer BE data did not match information in applications. It has taken
months for the manufacturers to get their drugs back on the WHO list.
Growing Anti-Malarial Ingredients
The delisting raised questions about the reliability of WHO's prequalification system, a skepticism shared by US health officials.
Even though WHO maintains that the incident demonstrates its ability to maintain high standards, PEPFAR requires drugs purchased
with US dollars to be approved by FDA, ostensibly to fend off charges that America foists lower-quality treatments on poor
Critics of the US position believe PEPFAR's real goal is to protect pharma patents. A commitment to purchasing FDA-approved
products translates into a commitment to buying more high-cost brand-name drugs—ultimately limiting the number of patients
treated. FDA's solution is to grant "tentative approval" to generic drugs that meet regulatory standards (and thus are eligible
for purchase by PEPFAR programs) but cannot be marketed in the United States for patent reasons. A May 2004 FDA guidance spells
out how manufacturers can develop and gain expedited review of FDCs and co-packaged ARVs.
Although many observers still regard FDA's approach as costly and unnecessary, the prospect of qualifying for purchase by
PEPFAR is attracting applicants, and the accelerated-review policy has helped bring new AIDS therapies to market quickly.
In January, Aspen Pharmacare of South Africa received the first tentative approval for a co-packaged drug regimen that includes
two tablets each of generic versions of Glaxo's Combivir (lamivudine/zidovudine) and Boehringer's Viramune (nevirapine). A
generic version of Combivir from India's Aurobindo Pharma gained tentative approval in July. FDA has also okayed many individual
generic AIDS treatments, including lamivudine, zidovudine, nevirapine, efavirenz, and stavudine—and a dozen applications are
in the review pipeline.
FDA has been able to approve PEPFAR applications in four to eight weeks. FDA deputy commissioner Murray Lumpkin says that
is because the Office of Generic Drugs (OGD) is providing a lot of hand-holding to generics companies, especially those unfamiliar
with agency policies. Speedy approvals require quality applications and early inspection of BE data and manufacturing facilities."