FDA’s first ‘political’ drug approval

Mifeprex: FDA’s first ‘political’ drug approval

Dickinson, James G

EXECUTIVE SUMMARY:

It was, like all FDA approval decisions, based in sound science and not in politics. That was the TV newsclip of sober-faced FDA Commissioner Jane Henney on the night the agency’s approval of RU-486, or Mifeprex (mifepristone) was announced. Her Director of Drugs, Janet Woodcock, held inflexibliy to the same line in ensuing weeks.

Clinton himself told reporters they should treat the approval “as the scientific and medical decision it was, and we should respect the fact that it was a nonpolitical inquiry.”

Although there has never been any suggestion that politicians with authority over the FDA have ever directed an approval (or non-approval) decision, this was probably the FDAs first “political” drug approval, orchestrated behind the scenes by the Clinton Administration and engaging the agency both as a banned import and a new drug through 12 years of political minefields.

No drug can be more political than one labeled as an abortifacient, and no advanced country could present a more political climate for a labeled abortifacient than the United States.

Unlike any drug before it, RU-486 made its most visible and energetic contacts with the agency in the context of presidential election campaign —

* in 1988, as France-based Roussel Uclaf’s (the RU in RU-486) fought for market status there, mifepristone became transatlantic contraband and an FDA-banned import, making an investigational new drug application here seem a politically unlikely project for Roussel Uclaf;

* in 1993, the incoming Clinton Administration, which was elected with strong support from prochoice activist groups, persuaded the RU-486 patent holder, then Hoechst-Roussel, to donate the patent to the Population Council and told FDA to lift an import alert that it had placed on it at the direction of the Bush Administration;

* in 1996, the Population Council filed the Clinton-sought NDA for RU-486, based on French and U.S. clinical studies in 2,100 women conducted by the Population Council; within three months, the FDA convened an advisory committee meeting on the drug and it was recommended for approval; three months later, the FDA issued an approvable letter conditional on the Population Council providing additional manufacturing, labeling, and other information in order to obtain final approval – that’s when the council’s contracted manufacturer, Gedeon Richter in Hungary, backed out, opening a four-year hiatus as the Population Council looked for alternative manufacturers and complying with FDA manufacturing requirements;

* in 2000, the FDA approved the NDA in good time for Clinton’s heir, Al Gore, to acclaim it as an election campaign asset (actually, the timing probably had more to do with the Population Council’s filing date and rigid statutory decision deadlines at the FDA than with string-pulling by the Gore campaign).

Another “political” element in the approval could be seen in the unprecedented FDA security shields injected into the official information released on Mifeprex. Because Roussel and others interested in producing RU-486 in the U.S. had been threatened with bombings, executive kidnappings, and other reprisals by anti-abortion fanatics over the years, the FDA agreed to conceal the identity and location of Mifeprex’s actual manufacturer.

That had the effect of shielding the secret manufacturer – rumored to be located in China – from public exposure of its regulatory status, with respect to such technical aspects as good manufacturing practices and product quality issues. No other drug manufacturer enjoys such government shelter from public embarrassment for its production shortcomings.

This prompted some on Capitol Hill and in the media to question Henney’s provocative declaration that the approval was strictly scientific and not political.

Among them, anti-abortion Arkansas Republican Senator Tim Hutchinson wrote Henney, asking her to at least confirm that the drug was being manufactured outside the U.S. and to name the country. “If your response does not provide an explicit answer, please cite the legal authority to withhold the information,” Hutchinson wrote.

His letter also asked Henney to provide information about the extent to which the FDA assisted Roussel Uclaf and the Population Council in locating a manufacturer and a distributor for RU– 486. The manufacturer remains secret, but the distributor is a mysterious company called Danco Laboratories, ostensibly based in New York but with no listed telephone number there.

Hutchinson is co-sponsoring with Rep. Tom A. Coburn (R.-Okla.) a bill under which physicians who offer Mifeprex would have to know how to perform surgical abortions, hold admitting privileges at a hospital no more than an hour from their offices, and meet other conditions. These had been among a raft of restrictions the FDA had earlier considered but then lifted from its final conditions of -approval, which simply limit the drug to administration in the office of any physician who can “accurately determine the duration of a patient’s pregnancy and detect an ectopic (or tubal) pregnancy,” according to an FDA news release. “Physicians who prescribe mifepristone must also be able to provide surgical intervention in cases of incomplete abortion or severe bleeding – or they must have made plans in advance to provide such care through others.”

This is an intensely political element of the approval, and one on which FDA officials were uncharacteristically reluctant to elaborate in the heat of the election campaign. The original restrictions they had considered, and that are demanded in the Hutchinson-Coburn bill, would “needlessly” limit access to Mifeprex, pro-abortion activists argued.

Question: is it the FDA’s mission to “maximize” or “minimize” chemical abortions? The agency’s charter is to be neutral in such matters, but its decision to eliminate the Hutchinson-Coburn restrictions arguably had the effect of maximizing chemical abortions via Mifeprex – a result desired by the Clinton-Gore machine.

Other lawmakers quickly weighed in, buffeting the agency with political issues. North Carolina Republican Senator Jesse Helms wrote, seeking answers to questions about whether Mifeprex’s secret manufacturer was owned by the Chinese government, used coercive or slave labor, or produced drugs used in the Chinese family planning program.

The chairman of the House Republican Conference, J.C. Watts (R.-Okla.), vowed to launch an investigation into “who is exporting this pill and what it actually contains.”

Mary Pendergast, who was former– Commissioner David Kessler’s senior advisor and deputy, and now works for Elan Pharmaceuticals, says she doubts there has ever been a politically influenced approval at FDA – including this one. The closest political contact with an approval decision she ever saw, she says, is when colleagues called certain lawmakers on Capitol Hill as a courtesy to let them know a few hours in advance that a significant approval had occurred that day.

Other former FDA senior officials are not so sure. Former Associate Chief Counsel for Drugs William W Vodra sees patterns in RU-486’s history, including the issuance of the 1989 import alert by then– Commissioner Frank E. Young in the first months of the Bush Administration, that suggest political influence at the highest levels against the drug.

Hutchinson’s question about how much the FDA was involved in finding a second manufacturer for Mifeprex taps a sensitive issue for an agency that does not want to project a “political” image in drug approvals. The FDA has scouted out potential manufacturers for drug sponsors before, but only under its so-called “orphan drug” statutory authority, in efforts to find sponsors for medically necessary therapies for rare diseases. However, pregnancy is not a rare disease.

Pendergast doubts that the Food and Drug Administration ever did “shop” for entities willing to submit RU-486. Linking parties in the sparse landscape of orphan diseases is something the FDA might well do, she says, but in the turbulent and over-populated world of women’s health activists, the Food and Drug Administration’s efforts would hardly be needed.

The Population Council, which has been highly secretive about the regulatory and manufacturing details of its RU-486 project and declined to participate in research for this article on those aspects, secured U.S. rights to the drug from Hoechst-Roussel (as it was then known) in 1994.

Naive in how to proceed from there, it then found an entrepreneur, Joseph Pike, who it felt could help find a pharmaceutical manufacturer. Danco Laboratories was set up by Pike as a distributor and to contract with manufacturer Gedeon Richter in Hungary. Later, the council discovered that Pike was a disbarred lawyer, and it severed its relationship with him. Although the name Danco Laboratories survived the rupture, council spokesperson Sandra Waldman said the company itself was restructured. The turmoil, however, saw the loss of Gedeon Richter as Danco’s manufacturer of mifepristone, and the Population Council had to begin its search all over again.

The Wall Street Journal reported in September that Danco Laboratories’ chief executive officer now is Roy Karnovsky, a former 20-year Merck employee and marketing executive who does not talk to the media. Financial backing had been in the form of grants and loans from foundations set up by Warren Buffett, George Soros, and the late David Packard, the Journal reported.

Although the Population Council describes Danco Laboratories as a New York-based women’s health pharmaceutical company, it has no telephone listing in that city and its publicity is handled by a company in Seattle, Wash.

The furtiveness, even paranoia, surrounding this drug and its producers may indeed all be justified by prudent security needs. But it also looks a lot like the Food and Drug Administration’s first political drug approval.

Copyright CPS Communications Nov 2000

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