E-DRUG: US FDA approves South African generic ARV (2)
Aspen's FDA Approval Weak Evidence of the Effectiveness of the FDA
The announcement that Aspen Pharmacare of S. Africa has received approval
for co-packaged Lamivudine/Zidovudine and Nevirparine through the FDA
fast-track marketing approval process represents a glimmer of progress in
what otherwise still remains a duplicative, costly, delayed, and ultimately
flawed U.S. review process.
Mark Dybul, second in charge at the Office of the U.S. Global AIDS
Initiative hopes that this one approval will "silence critics" and that
they will now rally behind a unilateralist effort by the U.S. to be the
final arbiter of quality, safety, and efficacy of medicines used to battle
acquired immune deficiency. For activists, however, this is yet another
example of too little, too late, and too imperial.
The first and still valid criticism of the FDA Fast Track Approval Process
is that it is unnecessarily duplicative. The WHO already had a
prequalification project for listing AIDS medicines of proven safety,
efficacy, and quality and listed qualifying generic medicines as early as
December 2003 - fourteen months before the first U.S. approval of an
on-patent ARV. Before listing a prequalified medicine, the WHO required
manufacturers to prove Good Manufacturing Practices at the particular plant
where the medicines was produced and it also required rigorous, world-class
proof of the bio-equivalence of the generic medicines to its brand name
counterpart (proving bioequivalence means that the active ingredient is
available in the body at the same rate and in the same quantity and quality
for the two products).
Admittedly, the WHO went through a rough-patch of adverse publicity
orchestrated by the U.S. pharmaceutical industry and its chorus of
right-wing ideologues and publicists at the Hudson Institute, American
Enterprise Institute, and the AIDS Responsibility (sic) Project, when
several Indian manufacturers including Cipla, Ranbaxy, and Hetero were
required to delist their ARV products because of poor record keeping
practices as the independent contract research organizations (CROs) that
conducted their bioequivalence studies. Contrary to pro-PhRMA claims,
however, the WHO and the Indian generic producers acted promptly to delist
their products and to undertake new bioequivalency studies. Cipla's
products have already been relisted at the WHO, but of course dishonest
PhRMA shills have neglected to retract their slanders against generic
producers and/or the WHO.
The U.S. went the unilateralist and duplicative route for one reason only -
to reassert the hegemony of its pharmaceutical industry of its captive
agency, the Food and Drug Administration. What is particularly galling in
the present circumstances is that the U.S. could oppose "giving Africans
medicines that haven't been approved for Americans" when in fact the FDA
was not even set up to give such approval until May of last year. And the
FDA's approval process and watchdog status for safeguarding consumer's
interests is hardly squeaky clean in the aftermath of the Vioxx scandal and
its belated black-box warning about suicide risks for youthful consumers of
In addition to being duplicative, the FDA tentative process is unduly
expensive. The U.S. likes to brag that it has been willing to waive the
normal $500,000 filing fee, but foreign generic companies are frequently
required to conduct new and costly bioequivalence studies using U.S.
registered medicines as the reference product instead of identical European
products which they had previously used to gain WHO prequalification.
(U.S. drug companies could allow generic companies to short cut these
duplicative studies if they would give so-called "reference rights" to the
generic producers, confirming the equivalence of the European and U.S.
products, but so far they have frequently refused to do so.) Moreover,
putting together the registration application file is inordinately complex
under picayune FDA regulations and requires not only reams of paper but an
army of specialized lawyers.
Moreover, it's deeply ironic to call the FDA process "fast-track" when
"slow-track" would be a better designation. The U.S. announced it
expedited procedures in May of 2004 and it has taken generic producers over
eight months to amass the necessary paperwork. Mark Dybul is bragging that
the approval process only took two weeks after Aspen submitted its final
dossier, but he neglects to mention the months and months of consultations
and redocumentation that were required to put together an application file
that could finally cut through the red-tape and Byzantine rules at the FDA.
We know for a fact that other generic producers, including Indian giants
like Ranbaxy, have been working since last summer to dot every "i" and
cross every "t" but that they still have not succeeded in getting a U.S.
stamp of approval. It's hard to call this process fast when you're a
person living with AIDS whose CD-4 cell count is plummeting every day.
However, the most deeply troubling aspect of the FDA tentative approval
process is that it is incomplete - that it cannot yet grant even tentative
approvals for the newest AIDS medicines. Because of data-protection rules
in U.S. law, rules that prohibit the FDA for five years from confirming the
safety and efficacy of bioequivalent generic products by even indirect
reference against marketing-approval dossiers submitted by originator
companies, the U.S. Fast Track process grinds to a halt for the newest
medicines like tenofovir.
It's fine that a PhRMA-favored generic company in South Africa has finally
gotten approval for some of the first-line generic medicines needed for
lower cost ARV therapy (Aspen has announced that it will sell at
approximately $200 per year versus nearly $600 for the mostly heavily
discounted brand name equivalents). It is even better that activists in
South African forced GlaxoSmithKline and Boehringer-Ingelheim to grant
broader and cheaper licenses that will permit Aspen to sell its ARVs
regionally throughout Southern Africa. However, Aspen has no plans yet to
market easier-to-use triple-fixed-dose product like those manufactured by
Cipla and Ranbaxy.
Professor Brook K. Baker, Health GAP
Northeastern University School of Law
400 Huntington Ave.
Boston, MA 02124 USA