Comments from the food and drug administration

Abstract

From the Office of Scientific Coordination, Bureau of Drugs, Food and Drug Administration, Rockville. Maryland 20852. Requests for reprints should be addressed to Dr. John G. Harter. Presented at the New York Heart Association Conference on Pharmacological and Clinical Control of Cardiovascular Drugs-Controversies in Cardiology, The Waldorf-Astoria, New York, New York, January 22, 1974. *Present address: Division of CardiivascularRenal Drug Products, PKLN 188-45 (HFD110). 5800 Fishers Lane, Rockville, Maryland 20852. The New York Heart Association played an active role in helping the FDA decide what to do about the digoxin problem, which was discovered by members of the New York Heart Association 2 years ago. The USP also cooperated with the FDA. In November 1974 the USP published an Interim Revision which established dissolution rate standards for digoxin products. As you will see, this cooperation is an essential part of our program to deal with digoxin. On January 14, 1974, about 610,000 copies of the FDA Bulletin were mailed out to each of you-doctors, pharmacists, dentists and other health professionals. In addition, we had a meeting with the manufacturers of digoxin (there are about 30) and told them about the new requirements for digoxin. These requirements were published in the Federal Register today, so it is appropriate that we discuss them. The Federal Register notice is some nine triple column pages. There are 150 references. The FDA has taken longer to act than many of our critics have thought we should, but our goal was not to try to initiate simple recalls to take poor products off the market, but to develop a plan to accomplish Withering’s objectives as outlined by Dr. Butler [I]that is to bring uniformity to digoxin products. We thought that initiating recalls, with manufacturers reformulating to suit their commercial needs, would create more confusion and hazard to you and to your patients than if we came to grips with the problem on a more comprehensive medical basis. We have created a precedent of sorts with our action in the Federal Register by taking a pre-1938 drug which manufacturers can make and distribute without telling us how they make it, its inactive ingredients, manufacturing and quality control procedures, etc., and we have said, “This needs to be a new drug because of its potential for toxicity and its need for relabeling and, it now comes under the new drug regulations. Manufacturers will now have to file and tell us the ingredients and the manufacturing process and let us know when they change them.” We have set a number of requirements that they will have to meet in order to market the drug. One of these is that bioavailability testing is required on all oral digoxin products. Another is that the dissolution test will be used by the FDA for certification of each batch of digoxin tablets before it can be released, and that the digoxin tablets will be divided into essentially three categories for regulatory purposes. As an aside, one of the questions most frequently raised by manufacturers was why bioavailability testing and not just the dissolution test since the dissolution test only costs about $50, whereas the bioavailability test costs about $5,000?