ORPHAN DESIGNATION PROCESS WILL BE TIGHTENED TO ELIMINATE "SALAMI-SLICING" OF INDICATIONS FOR DRUGS WITH LARGE POTENTIAL PATIENT POPULATIONS -- FDA’s HAFFNER

FDA plans to tighten its orphan designation process so that products with appropriate "unique" populations are chosen to receive orphan status, FDA Office of Orphan Products Development Director Marlene Haffner, MD, said at a June 7 session of the Drug Information Association's 26th annual meeting in San Francisco. Discussing the orphan products office's future plans, Haffner said: "We feel that the designation process does need to be tightened a bit." She noted that there has been some use of the "the salami-slicing technique" by companies trying to carve a smaller patient population out of a larger one for their product in order to receive the seven-year orphan exclusivity. "Sometimes salami-slicing [to find] a small population is appropriate, but sometimes it's not," Haffner said. "And we're going to be tightening down on that." The FDAer told the DIA audience that "some of you will periodically be getting letters that say -- 'we really think that this population is not a unique population, but is part of a whole population, which can be adequately treated by this drug and therefore your population is greater than 200,000."' The definition of an orphan drug is based on an estimated patient population size of fewer than 200,000 patients. Haffner noted that pending amendments to the Orphan Drug Act would require sponsors of orphan products to make projections of how many persons will be affected by the disease or condition three years from the date of request for orphan designation, rather than of the size of the patient population at the time of the request. The legislation, introduced by Rep. Waxman (D-Calif.) on April 26, will authorize FDA to nullify the exclusivity benefit for any orphan product once the indicated patient population exceeds the threshold 200,000. At present, most of the designated orphan products are targeted at appropriate patient populations "below 50,000," Haffner said. At the end of 1989, "we had 89 products that were designated for populations less than 10,000 patients," she noted. "We do think that we're beginning to see an increase in the other side of that spectrum, but it's a small situation at the present time and not one that has clearly shown a trend." Regarding the continued delays in FDA's issuance of orphan drug regulations, Haffner noted that the agency has had its "difficulties in getting [the regs] through the system and they should be published...very shortly." The regs were originally scheduled to be released two years ago. FDA's latest regulatory agenda calls for their publication in October 1990 ("The Pink Sheet" April 30, p. 9). However, the regs could be delayed even further if Waxman's proposed amendments to the Orphan Drug Act make it through Congress during this session. Haffner added that "part of what is holding us up is a good definition within the agency of what are 'same' drugs and what are 'different' drugs. The real difficulty is in the biologic arena." FDA had tentatively scheduled an advisory committee meeting on June 29 to consider the similarities and differences of the erythropoietin molecules in Amgen's Epogen and Chugai-Upjohn's Marogen to determine whether both products can be marketed under the current orphan regulations. However, FDA is reportedly reconsidering whether to go ahead with that meeting. The Office of Orphan Products Development currently has 16 persons, whereas three years ago it had seven staffers, Haffner said. "So we more than doubled at a time when FDA has overall been shrinking." As of the end of 1989, the office had 446 requests for designation, and of those, 333 have been designated. To date, 46 orphan products have been approved. At the same DIA session, Center for Drug Evaluation and Research-Document Management and Reporting Branch Chief Ann Myers said that "there have been 31 Treatment INDs [applications] received as of the end of March. And of the 31, there have been 20 that have been for orphan drug products; a high percentage have been allowed to proceed." She noted that "four of the 20 orphans that have been submitted have been approved."