Manufacturers unsuccessful in arguing to the Food and Drug Administration that a generic drug is not equivalent to their brand product are increasingly carrying their arguments outside the agency. In the suit that preceded the successful outcome for Serono Laboratories, Somerset Pharmaceuticals, failed in court to block a generic selegiline(Drug information on selegiline) form of Eldepryl and according to a staff person at the FDA generics office, other manufacturers have sued and lost, including Bristol-Myers Squibb over cholestyr-amine (Questran); Glaxo Wellcome over clobetasol(Drug information on clobetasol) (Temovate); Fisons Corporation over cromolyn (Intal); and Schering Corporation, which brought four actions, a separate suit and appeal in each of two districts, over albuterol (Proventil).
In another tack, Coumadin (warfarin) manufacturer Dupont Pharma targeted state legislatures one year before the FDA approved a generic warfarin(Drug information on warfarin) in July, providing start-up funding for a multisponsored alliance to lobby against substitution without prescriber notification and for increased standards of bioequivalence for products having a narrow therapeutic index (NTI) (Dupont Pharma appears to be closely monitoring the market entry of the generic warfarin product from Barr Laboratories, and in August transmitted an unprecedented fax nationally to practitioners and pharmacies critical of educational materials prepared by Barr Laboratories, to which Barr issued its own nationally distributed fax response-Ed.)
Douglas Sporn, director of the FDA office of generic drugs, related the view of some long-term staffers in his office that this lobbying effort was "an aggressive approach" against generic competition. Roger Williams, Ph.D., Sporn's predecessor as director of the office of generic drugs, recently described this lobbying to Associated Press reporter Jim Drinkard as, "in the class of an economic challenge" rather than a scientific one.
Rick Glaub, of the Washington public relations firm Goddard Claussen, which launched the lobby as the Health Alliance for NTI Patient Safety, dismissed characterizations of the alliance as engaged in a battle between brand and generic drug manufacturers. He explained to Psychiatric Times that the alliance, whose sponsors include the American Psychiatric Association among other medical associations, does not contest the "prescribabilty" of NTI generic drugs as much as their "switchability." The list of approximately 30 generic medications having a narrow therapeutic index was compiled by the FDA and includes warfarin, extended release lithium and clonidine(Drug information on clonidine).
Glaub acknowledged that the FDA has been discussing the development of more stringent bioequivalence standards for these drugs within its Medical Policy Coordinating Committee, chaired by Robert Temple, M.D., associate director for medical policy. Glaub commented wryly, however, that the committee progress "has been described as moving with great dispatch, in geological terms."
Each of the manufacturers of reference brand products ("innovator," in the terminology of ANDA [Abbreviated New Drug Applications] approval regulations) that has sought remedies from outside the FDA has been unsuccessful or frustrated in using "citizens petitions," "petitions to stay" or in conferring with FDA staff to criticize ANDA data. In the case of Serono Laboratories, their 1992 citizens petition concerning the 1990 ANDA for Repronex went unanswered for over four years, despite an FDA regulation that requires the Agency to respond within 180 days.
Sporn told Psychiatric Times that the response to Serono Laboratories "was sent after the [Jan. 30, 1997] approval [of Repronex]." He conceded that the mandated response time for citizens' petitions is commonly violated by the agency, remarking that his office is "inundated by citizens' petitions," which he attributes generally to the profit motive of the innovator manufacturer wishing to protect market share rather than to valid concerns about equivalency. "It is fairly common for innovators to try to raise the bar, so to speak," Sporn said, when brand product patents are about to expire.
The protracted period for response is also the result, according to Sporn, of the agency viewing each petition as the basis for a potential lawsuit, and so undertaking extensive deliberations with the agency office of chief counsel. Another reason for delayed response is the lack of manpower, he lamented.
"We are receiving an increased number of [ANDA] applications at the same time as government downsizing, and our priority is review [applications] work before anything else," he went on to say. "It is sapping off resources here to review drug applications. We've had to spend more and more time meeting with attorneys, preparing for lawsuits."