A cup of vinegar and gall

The US calls the WHO's AIDS drugs approval system into question. Is it about safety or economics?

By Owen Dyer

In a move that leaves a bitter taste, the US government has started openly questioning the quality of a World Health Organisation (WHO) drug approval process that regulates generic AIDS drugs essential to the developing world.

International health charities are accusing the US of trying to wriggle out of commitments President Bush made last year when he announced his $15 billion Presidential Emergency Plan for AIDS Relief (PEPFAR). Rather than spending the money on cheap three-in-one generic formulations, the US Global AIDS Coordinator, Randall Tobias, proposes buying brand-name drugs from the US pharmaceutical industry. The plan, if implemented, would mean that only about a quarter the number of patients could be treated with the available money.

This move seems to fly in the face of the Doha (2001) and World Trade Organization(2002) agreements stipulating that patent rules could be overlooked in the case of AIDS drugs for the developing world, which the US signed up for. But now Mr Tobias, a former CEO of drug giant Eli Lilly, is saying that the WHO prequalification process, which monitors consistency and quality of generic AIDS drugs, doesn't meet the standards of FDA approval.

Addressing Congress on March 18, Mr Tobias said the US government's objections are motivated by concern for the safety of AIDS patients in developing countries. "We have been reading stories lately about some problems with some drugs around the world where people with the best of intentions have made acquisitions of drugs that have turned out to not have the consistency, and the safety and effectiveness that people had hoped," he said.

Health Canada's Health Protection Branch and European drug regulators have played a major role in developing the WHO prequalification program, including lending their staff to carry out inspections of manufacturing facilities. Since the generics contain the same active ingredients as the patented products, the process starts with the assumption that if dosage, consistency and quality meet acceptable standards, the drug should be approved.

Health Canada wouldn't comment on Mr Tobias' stance, but a spokesperson did say that, "Government officials have been hard at work to develop the regulatory proposals that respect the WTO declaration and ensure that medicines exported under this regime meet Canadian standards."

FDA CATCH 22
However, unlike the patented components of AIDS triple therapy, generic fixed-dose combination drugs combine all three medications in a single pill. The US argues that this could produce unexpected results, and says combination pills should be submitted for a full approval process. But since the US has refused to sign a confidentiality agreement that would permit FDA access to the generic drugs' data, the FDA is legally unable to review them. In light of this stalemate, Mr Tobias concludes that the US should spend its money on the individual patented drugs from US pharmaceutical companies.

On March 29, the US convened a special emergency meeting in Gaborone, Botswana to present its concerns to international AIDS and health organizations. Ellen 't Hoen, head of Policy & Research for Médecins Sans Frontières' Campaign for Access to Essential Medicines, attended the meeting and says US PEPFAR officials didn't budge on the issue of generic fixed-dose combination drugs. "In our experience every time we satisfy their concerns it seems they move the goalposts." says Ms 't Hoen. "The US says it needs internationally approved principles before it

can purchase non-FDA-approved drugs, but of course the real problem with these drugs in their eyes is that they aren't manufactured in the US. This was the elephant in the room that nobody could mention. So long as this issue is unresolved, there is a huge risk that parallel programs will develop. This would be a disaster in our eyes."

A QUESTION OF ECONOMICS
The cheapest generic combination pills cost about $183 per person a year under a price agreement negotiated with manufacturers by Bill Clinton. The same combination from brand-name companies costs about $735 per person per year. Moreover, patients would have to take six brand-name pills a day instead of two generics.

Sharonann Lynch, of the US-based AIDS charity Health Global Access Project, says the US government is simply trying to ensure that the money from the AIDS relief plan is spent domestic-ally. "These objections make no sense. The generic drugs are bioequivalent compounds, and the WHO prequalification process uses staff from Canadian and European regulatory bodies that the US recognises. This meeting is completely pointless. It's just filibustering."