The World Health Organization’s process for approving generic HIV drugs for use in developing countries is under intense criticism from a gay member of the Bush Administration, after 18 already-approved drugs were removed from the WHO prequalified list since May over inadequate bioequivalence data.

Abner Mason, a gay Republican member of the Presidential Advisory Council on HIV/AIDS, said the removal of those drugs from the WHO list of approved medicines validates a resolution passed by PACHA in March. The measure stipulated that generic drugs purchased with U.S. tax dollars must be approved by the Food & Drug Administration or meet a “standard of comparable scientific rigor.”

The resolution, which was drafted by Mason and approved unanimously by the 35-member advisory council, was intended to ensure that drugs purchased by the U.S. for use in other countries meet the same safety standards as drugs used by Americans, Mason said.

“What [the removal of the drugs] says is that we were certainly right to be cautious,” Mason said. It was “a terrible failure of oversight” by WHO to allow the drugs to be approved and used by patients in the first place, he said.

But some AIDS activists, who continue to discount Mason as “a lapdog of the pharmaceutical industry,” say the 18 drugs were de-listed because of “paperwork” glitches involving contractors who were hired to conduct bioequivalence tests to verify the data generic drug manufacturers presented to WHO.

The decision to remove the drugs from the approved medicines list actually highlights the vigilance and reliability of the WHO approval process, said Paul Davis, domestic policy director for Health GAP, an AIDS advocacy group that focuses on increasing global access to life-saving medicines.

“The drugs that were de-listed have n ot been shown to be of substandard quality [compared to their brand-name counterparts],” Davis said. “Even though the drugs actually work, WHO is stringent enough to de-list these products, so it sounds like evidence the process is working.”

‘Short-term pain’
The first two drugs that were yanked off the WHO list in May — generic versions of AZT and 3TC, both manufactured by India-based Cipla Ltd. — were reinstated Nov. 30 after new tests and inspections revealed that the generic drugs had the same bioequivalence as their brand-name versions, said Lembit Rago, WHO coordinator of Quality, Safety & Efficacy of Medicines.

Bioequivalence trials use healthy patients to find out if the concentration of a generic drug in the blood of a patient is equivalent to that of the original product, said Rago, who added that WHO dealt with the de-listing controversy in an “extremely transparent way.”

“This has been short-term pain with much more long-term gain because this is quite a rigorous process we are using now in terms of assessing bioequivalence,” Rago said during a telephone interview from his Switzerland office last week.

When announcing the de-listing of the generic HIV medications, the WHO said that “in principle” patients should cease using the de-listed medications, but added that “the risk of withholding treatment is higher than that of providing medicines whose bioequivalence is not proven, but which have demonstrated quality and safety.”

String of drugs de-listed
Established in 2001, the WHO Prequalification Project created a list of vital HIV medications for use in developing countries that met WHO safety standards.

AIDS activists credit the prequalification process with expediting the delivery of life-saving drugs to those most in need, and helping drive the cost of HIV medications down by giving generic drugs the WHO stamp of approval.

“Certainly thousands of people would have died had [the WHO] not made these drugs available,” said Rachel Cohen, U.S. director of Doctors Without Borders’ Campaign for Access to Essential Medicines.

A drug is added to the WHO prequalified list after the agency inspects the sites where the it is manufactured and evaluates the drug’s quality based on data provided to WHO by pharmaceutical companies.

Companies are also required to submit data from independent contractors verifying their bioequivalence results. Prior to May 2004, WHO reviewed the data from these contractors, but did not inspect the sites at which the trials were conducted, according to WHO’s Rago.

Less than 10 percent of European countries used to require inspections of the contractors conducting bioequivalence studies, which is why WHO did not originally make these inspections a requirement for a drug to a listed as an approved medicine, Rago said.

But on May 1, a directive from the European Commission went into effect requiring countries to carry out such inspections, which WHO began doing immediately.

On May 27, WHO removed the two Cipla drugs from its list of approved medicines after inspections of contractors’ labs revealed “serious discrepancies between the original results compiled by the [contractors] and the results presented to WHO by the manufacturers.”

Since the WHO could not accept the contractors’ data to verify the drugs’ bioequivalence, the drugs no longer met prequalification requirements and had to be de-listed, Rago said.

Two months later, on Aug. 4, the WHO removed three generic HIV drugs manufactured by India-based Ranbaxy Laboratories Ltd., for the same reason.
On Nov. 9, Ranbaxy voluntarily withdrew all seven of its remaining antiretroviral drugs from the WHO list so that it could review and resubmit its data on the drugs’ bioequivalence.

India-based Hetero Drugs Ltd., also voluntarily withdrew its six antiretrovirals from the WHO list on Nov. 19 so that it could review and resubmit its data.
Inspection of the labs where independent contractors conduct bioequivalence studies is now a standard requirement for a drug to be prequalified by WHO, Rago said.

‘A moral and a money issue’
But critics of WHO said the de-listing of the 18 drugs is indicative of a lack of safeguards in the WHO approval process, and harshly accused the health body of wasting money on unproven medicines and putting the lives of poor people at risk.

“The WHO told the entire world these drugs were prequalified, so the question is why would they be doing studies now on the bioequivalence,” said Carol Adelman, a physician who serves as director of the Center for Science & Public Policy at the Hudson Institute, a conservative think tank based in Washington D.C.

With U.S. taxpayers being the largest contributor to the Global AIDS Fund, which is used to buy HIV drugs for developing countries, they have a right to know if their money is be

email   password The following comments were posted by our readers and were not edited by SOVO.  We ask that you treat others with respect; any post deemed offensive will be removed.