[Ip-health] Post Prequalification Rigor at the WHO

[B.Baker@neu.edu]

Post Prequalification Rigor at the WHO
Brook K. Baker, Health GAP
June 16, 2004

The New York Times reports today (Altman and McNeil, U.N. Agency Drops 2
Drugs for AIDS Care Worldwide) that two generic antiretrovirals produced by
Cipla of India, namely lamivudine (4TC) 150 mg tablets and the fixed-dose
combination of lamivudine and zidovudine (AZT) have been removed from the
WHO list of prequalified medicines.  Cipla had commissioned a Contract
Research Organization (CRO) in India to conducts its bioequivalence test on
these two products, and a subsequent review by the WHO found that the CRO's
documents did not meeting the standards for Good Clinical Practices and
Good Laboratory Practices.   Although it is quite likely that Cipla's
products are in fact bioequivalent to their brand name counterparts (one of
them has been separately approved by the FDA), the WHO suspended
prequalification until Cipla resubmits new data, which it intends to do by
the end of July.

Although the U.S. and its think-tank proxies might try to argue that
suspension confirms concerns about the rigor of the WHO Prequalification
Project, the opposite is true.  WHO conducted inspections of the
independent testing lab, decertified products when the lab's record-keeping
was substandard, and notified the relevant public via its website.  This is
evidence of a global public health agency that takes its mandate seriously.

Similarly, this is not a wholesale indictment of the quality, safety, and
efficacy of Cipla's ARVs or of other Indian generic products, but rather
the importance of dotting every "i" twice when selecting subcontractors for
laboratory services.  Cipla has many other products which are still
prequalified at the WHO based on unquestioned bioequivalence studies
analyzed at other labs, including Cipla's WHO-recommended triple-fixed
dose-combination, Triomune.  Moreover, one of the products temporarily
suspending, lamivudine, has received tentative approval from the FDA based
on alternative bioequivalence studies conducted in the U.S.  Likewise, ARVs
from two other Indian companies, Hetero and Rambaxy, are still on the WHO
list.  Thus, generic ARVs can continue to provide standard quality
medicines at the lowest cost and should be procured accordingly

Both of the challenged medicines are still registered by national drug
regulatory agencies in many developing countries and thus may still be
lawfully prescribed for in-country use.  Nonetheless, careful health
providers may temporarily suspend product use until the medicines are
re-listed at the WHO, so long as therapeutically equivalent products are
available and patient treatment is not interrupted.  Similarly, delisting
does not automatically require a change of medicines for projects receiving
funding from the Global Fund to Fight AIDS, TB, and Malaria, but would do
so as of Jan. 1, 2005.

Although substandard procedures and record-keeping at CROs is regrettable,
it happens in the U.S. as well as at the WHO, and it has affected brandname
as well as generic drugs.  The lapse here seems to have been innocent
enough, but in other contexts drug companies developing high-stakes
innovative products have been known to cook the books.  Thus, in a
companion article in the Times today, the American Medical Association has
joined other medical groups in calling for dissemination of information
concerning all clinical trials, including those with unfavorable results.
In this regard, GlaxoSmithKline, the world's major producer of proprietary
HIV medicines, has just been sued in New York for having failed to publish
reports on concerning adverse effects in clinical trials, including suicide
among adolescents taking its anti-depressant, paroxetine. Paroxetine
generated $533 million dollars in sales in the first quarter of 2004 alone,
showing just how profitable monopoly-priced, patent-protected can be.