[Ip-health] Tobias FDA-Approval Hoopla

[B.Baker@neu.edu]

As reported on April 28, 2004, Ambassador Andrew Tobias, U.S. Global AIDS
Coordinator, has chosen Africa to continue his disinformation campaign
against generic AIDS drugs and against the WHO Pre-Qualification Project.
He said:  "Maybe these drug are safe and effective ... Maybe they aren't.
Nobody really knows."  As to the WHO Pre-Qualfication Project, he said that
the U.S. wants a more transparent and stringent review process, maybe at
the FDA and maybe somewhere else.

As a technical matter, generic companies in the U.S. cannot lawfully obtain
final marketing approval for generic medicines under FDA
abbreviated-new-drug-registration regulations until the end of the period
of patent protection.  However, the so-called Bolar provision in U.S. drug
registration law allows a generic company to formulate a new bio-equivalent
generic drug and to amass a drug registration portfolio during a patent and
even to seek pre-approval at the FDA.  (The E.U. has no such Bolar
provision).  However, in seeking such regulatory approval, the generic
company must certify its knowledge of conflicting patents and must
ordinarily acknowledge that it will not be seeking final marketing approval
until patent expiration.  (In the rare case, some generics choose to
challenge an Orange Book patent listing which results in an automatic
30-month stay while the patent challenge is being litigated).

Generic companies have rarely bothered to seek pre-approval and to register
their products in the U.S. until the very end of the patent term.  This is
a matter of economic practicality.  Developing technologies for efficient
drug formulation at high quality can be expensive.  Likewise, testing is
required to demonstrate the bio-equivalence and uniform potency of the new
generic.  Finally, it costs thousands of dollars in attorney's fees (est.
$100,000) to usher even an abbreviated application through the labyrinth
FDA process.

As a simple matter, generic companies have not been willing to make this
investment early in the life of a patent, even if the five-year data
exclusivity period has expired, because of the economic uncertainty that
the generic entrant will be economically viable in the distant future.
After all, a new break-through could completely undermine the existing
therapy.  Or an originator's ever-greening strategy might involve a minor
improvement that nonetheless extends the patent bar.  Most companies simply
agree that it's better to wait to the end, at least with respect to the
U.S. market.

U.S. PEPFAR officials know all this and they know that none of the
manufacturers of generic ARVs have considered it economically viable to
seek pre-approval in the U.S.  These same officials know that it is totally
illegal to seek such pre-approval before actual patent expiration in the
E.U.

Moreover, until the recently devised U.S. PEPFAR policy was announced,
there was no need for a generic company to obtain regulatory approval from
the U.S. (or from stringent European, Canadian, or Japanese drug
registration agencies) in order to register and sell its product in a
developing country.  Of course, the PEPFAR FDA rule changes all of that.

A Wall Street Journal article quotes an anonymous FDA official about
possible expedited pre-approvals at the FDA that might take as little as
1-2 months.  However, the U.S. has previously announced that it will not
even set up its parallel process (at the FDA or elsewhere with a private
contractor) until September.  In addition, the U.S. and the U.S. drug
industry continue to espouse that clinical trials may be necessary to
confirm the longer-term efficacy of a generic FDC, which miraculously, even
though bio-equivalent, might somehow promote more resistance than an
identical three-drug regime of single-dose products.

At the end of the day, the U.S. is still slandering the WHO
Pre-qualification Project - its stringency and its transparency.  It has
not, to our knowledge, formally asked for access to the underlying evidence
of bio-equivalence and GMP.  Although it alleges that it is in on-going
negotiations with the WHO, the process drags on and on at the same time
that PEPFAR recipients are being required to procure and utilize FDA
approved, brandname drugs only.

PEPFAR's pseudo-science of quality continues to confound a coordinated and
proportionate response to the pandemic.  Shame once again on ex-drug
company exec, Randall Tobias, who should and does know much better.

Brook