Back then, the early FDA could not actually pursue manufacturers or products until they had shown that a problem actually existed either via showing clinical harm or by demonstrating the presence of known dangerous substances. This is similar, by the way (and to the horror of many of us) to the way “nutritional supplements” are regulated (not) today largely thanks to Orin Hatch.
This early approach changed dramatically in 1962 with the passage of the Kefhauver-Harris amendment to the Food and Drugs Act. The impetus for this change was the devastation of birth deformities as the result of the use of thalidomide to control the nausea of pregnancy and the resulting political pressure for change. This amendment required manufacturers to demonstrate not just safety but also efficacy of any proposed therapeutic.
Fast-forward to the early 2000s and clinical trials to prove safety and efficacy of new antibiotics. For years, the Infectious Diseases Society of America and the FDA collaborated in the promulgation of guidelines setting out the requirements for the design of these studies. Starting around 2000, the statisticians at FDA began to balk at the fundamental statistical foundation for the approach that had been used since the days of penicillin. That approach called for studies comparing a new antibiotic to an old, approved and standard of care antibiotic where the new drug had to be shown to be not inferior to the standard treatment. This is quite different than other clinical domains where new therapies are shown to be superior to placebo. As we all know, it is generally not acceptable to treat patients with a life-threatening disease (many if not most bacterial infections) with a placebo when we know that a safe and effective therapy already exists. Hence the so-called non-inferiority approach. The FDA then gradually tightened the statistical margins required resulting in increased costs of trials, lengthened time to market and decreased profits for new antibiotics. Then came the Ketek scandal of 2006 and the major involvement of politics in FDA “business.” Ketek (telithromycin) is an antibiotic developed by Sanofi for the treatment of pneumonia, sinusitis and bronchitis. It was approved in the US in a twisted set of data evaluations by the agency where, virtually uniquely, post-market safety data from Europe where the drug had already been on the market for a period of time was used to help justify the approval. After a year or two on the US market, several cases of severe liver injury were linked to Ketek and the scandal was born. Public Citizen cried foul relying on FDA insiders who objected to the way Ketek was approved to begin with. Public Citizen in turn pressured congress, especially representatives Markey and Grassley, to investigate the FDA. Markey and Grassley threatened the FDA with an investigation. This resulted in FDA panic mode as they feverishly began to assemble all the documents and materials that such an investigation would require. Rather than face the congressional investigations threatened by Markey and Grassley, FDA reacted by essentially carrying out their own investigation in public. There they crucified not only their own officials who led the approval of the drug, but also the clinical trial requirements for antibiotics. The latter response led to a point where it was no longer possible to carry out new antibiotic development and therefore where new antibiotics no longer had a clear path to approval. And all this was clearly based more on politics than the cold hard facts of the science. The FDA lost many dedicated and experienced antibiotic experts as a result of the Ketek scandal. This is all detailed in my book (you can just download the chapter on FDA if you want). As we all know, all’s well that ends well – but that was after at least six years of antibiotic development drought and the loss of hundreds of antibiotic researchers.
Fast forward to covid. OK. Political influence might be erring on the side of less scientific stringency as opposed to more stringency – but there is no doubt that the FDA, as much as they claim to be science based, is susceptible to political pressure. And this is nothing new . . .