THE FDA TEN YEARS AFTER THE KEFAUVER-HARRIS AMENDMENTS LEO E. HOLUSTER* Five years ago I participated in a guest editorial on the impact of the 1962 legislation on the function of the Food and Drug Administration [I]. We concluded: (1) that the new powers given the FDA were beneficial, (2) that no one would seriously propose that the law be repealed, (3) that many of the abuses which the law intended to correct had been corrected, and (4) that the time had come to interpret more liberally those provisions of the law which, as they were currently read, were cumbersome and vexing and possibly impeded the development of new drugs. It would be satisfying to say that during the subsequent 5 years the remaining problems have been eliminated, but unfortunately such is not the case. Problems still remain, but some positive steps are being taken to rectify them. A major drug disaster such as the thalidomide affair, which provided the major impetus for the 1962 legislation, has not occurred. Luckily, adverse effects of thalidomide were slight in the United States as compared with other countries, largely due to good fortune rather than sound laws or sound judgment. The most serious drug disaster of the past 10 years was the epidemic in the United Kingdom of an estimated 3,500 excess deaths, mainly in adolescent asthmatics, over a 6-year period following the introduction of a stronger isoproterenol spray for self-administration as well as for self-prescription [2]. This issue was not faced by the FDA, since there had been no pressure to market this preparation in the United States. However, if this had been the case, one might assume that the new preparation would have been treated as a new drug, undergoing considerable clinical trial prior to approval of a new drug application (NDA), and that these mechanisms would have prevented such an occurrence. While there is no assurance that we are forever safe from future serious misadventures with drugs, we are undoubtedly better off than we were, and possibly better off than many other countries. •Associate professor of medicine, Stanford University School of Medicine, Palo Alto, California 94304. I thank Carl C. Pfeiffer for his most helpful suggestions. 242 I Leo E. Hollister · FDA Amendments One might think that, living under this umbrella of protection, we should all have unstinting praise for the FDA. Rather, the opposite is true. Complaints about the operations of the FDA and their implications for the health of the country continue. Major Complaints 1. Impeding the innovation of new drugs. —The number of new drugs (often equated with new chemical entities) appearing on the American market has declined sharply over the past decade, although a slight decline was evident earlier. To withhold a useful drug unduly may be as injurious to our society as releasing one that is not useful. Is it possible that overassiduous demands for new drugs are holding back many useful ones from the market? The answer is, Yes, if one considers the large number of drugs available elsewhere in the world which most American physicians have never heard of: the ^-adrenergic stimulating drug, salbutamol; the antihypertensives , diazoxide and bethanidine; the antiarrhythmic agent, bretylium ; several new ^-adrenergic blocking drugs, including practolol; the antiinflammatory drug, ibuprofene; the antibacterial, trimethaprim (despite the fact that it was discovered in this country); a new approach to treating bronchial asthma with disodium cromoglycolate; and a treatment for gastric ulcer, carbenoloxone.1 The situation in regard to drugs used by cardiologists is a case in point. When a symposium was proposed on "New Drugs for Heart Disease," the alternative title "Drugs American Cardiologists Would Like to Be Able to Use" seemed more appropriate. Not all drugs unfamiliar to U.S. physicians are necessarily completely proved, and some may turn out not to be desirable. Nor is it always the fault ofthe FDA that these drugs are not promoted for the American market. Still, the formidable impediments to getting a New Drug Application (NDA) approved in this country must certainly be a consideration when a company considers marketing a new drug in the United States. Several of us were asked recently to list therapeutic advances to...