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FDA's clinical efficacy standard for approving therapeutics may be getting a second look from the agency's Center for Biologics Evaluation & Research (CBER). Donald Burlington, MD, head of the biological INDs division declared the agency's interest in "reexamining" the standard for proving efficacy during a presentation at the Regulatory Affairs Professionals Society annual meeting on Sept. 28. Among the policy issues being considered by FDA, Burlington reported, is the question of whether clinical outcome or biological activity is the most accurate determinant of efficacy. Burlington asked: "Is the proper standard of efficacy one of clinical benefit. . . ? Or is the proper standard of efficacy one of biological activity?" Noting that the benefit standard is "certainly the position that the agency has been pursuing recently," he urged industry input on the direction the agency should take. The FDAer also addressed the regulatory distinction between drugs and biologics and the question of which center handles which review at FDA. "When you have a new product or a new class of products and you want to know where it goes, you can either take a flier and send it someplace and see if it sticks, or you can ask us," he said. However, Burlington cautioned, the agency cannot make such distinctions "months and months in advance because it takes a lot of our time and effort and the situation might be different when you've actually got a product ready to put before us." He added that if a company takes "a flier and just sends it in, there is a risk that it may be reassigned." Xoma VP Medical and Regulatory Affairs Samuel Ackerman, MD, pointed out what he views as "the central dilemma of biological product development" -- the lack of "synchrony between the clinical development and the manufacturing development." Ackerman was previously the head of IND reviews for FDA's biologicals review effort. The Xoma exec observed that "it is difficult, if not impossible, to avoid manufacturing changes along the way." He said Xoma attempts to avoid major disruptions during clinicals when making manufacturing changes by having "a fully characterized product as soon as" possible. Ackerman advised trying to accomplish "the manufacturing changes . . . at a time that's not going to be critical in terms of your clinical trials. Burlington noted that FDA is continuing to "struggle" with how the agency should interpret the export provision for partially processed biological materials contained within the Drug Export Act of 1986. In order to interpret the provision, FDA must first define "partially processed biologicals," he said. "Our current approach and consideration is that it should be something that requires additional significant manufacturing to put it into a form that would be analogous to a purified drug substance." The material should require "additional purification, chemical alteration, inactivation, or some other substantive manufacturing step before it gets to that purified substance," Burlington said. FDA continues "to discuss this and needs the input of industry in formulation of this policy," he added. FDA Commissioner Young, at an Industrial Biotechnology Association meeting last October, said that FDA's definition of "partially processed biologicals" will be part of a package of agency guidelines on the export of intermediate biologicals ("The Pink Sheet" Nov. 9, 1987, T&G-3).