Insulin & Penicillin Standards

Frederick G. Banting, John J.Macleod, Charles H. Best, and James B. Collip from the University of Toronto successfully extracted insulin for therapeutic use in 1922. The University of Toronto's patent was to expire Christmas Eve 1941, but by November a public standard had yet to be developed. To respond to the emergency need for insulin standards, the USP formed an Insulin Advisory Committee. Chaired by FDA's Herbert O. Calvery, this committee announced the development of a USP Reference Standard for insulin on December 1, 1941. USP and the American Medical Association also appealed to Congress to give FDA authority over insulin certification. The committee's efforts were successful. By the December 25th deadline the FDCA had been amended to require FDA certification of each batch of insulin prior to distribution and an official insulin standard was issued in USP's Interim Revision Announcement No. 4.

Penicillin Standard and Antibiotic Certification

Although penicillin was discovered in 1928, scientists were still unable to mass produce the drug in the early 1940s. Hastened by causalities of WWII, Howard Florey and his colleagues at Oxford appealed to the U.S. government and industry to solve this production problem. Mass production methods were soon developed and USP, FDA, National Institutes of Health, and The War Production Board held a series of conferences in 1943 and 1944 to develop penicillin standards. By March 1944, the Subcommittee on Scope approved penicillin standard for admission to the USP, and in 1945, the FDCA was amended to require FDA certification of penicillin. Subsequent amendments extended this certification to encompass all antibiotics. As a result, the regulatory scheme for antibiotics became different from that of other drugs (until essentially merged with the scheme for other drugs with the 1997 FDA Modernization Act). Antibiotics had to pass FDA's batch certification program and be approved batch by batch. They also had to adhere to drug monographs published by FDA, rather than, USP. This process was costly and time consuming for FDA and manufacturers. It also made it redundant for USP to publish full monographs for antibiotics; instead, the USP included brief monographs that contained references to FDA's standards. In 1971, USP's Thomas Macek first proposed that USP develop "better antibiotics tests and standards" than those "now being used in the FDA certification process," and in 1977, Richard Crout of the Bureau of Drugs raised the possibility of USP taking a more active role in antibiotic standardization. The same year William Heller and Joseph Valentino discussed with FDA Compendial Liaison staff the possibility of USP distributing antibiotic reference standards and publishing complete antibiotic monographs.

By 1978, USP had taken over responsibility for creating antibiotic reference standards, previously prepared by FDA. A Joint Committee on Antibiotic Quality was formed to develop and maintain up-to-date standards under the assumption that the dissolution of the certification program was inevitable. In 1982, this was followed by FDA's elimination of its batch certification program in favor of relying on compendial specifications and FDA GMP Regulations and Policies, anticipating the 1997 statutory changes.