DITORIAL
A Brief History of FDA Compounding Oversight
This issue highlights a series of challenging pediatric dermatology cases organized by Sarah L. Chamlin, MD, an outstanding pediatric dermatologist and the dermatology section editor of Pediatric Annals. Be sure to look at each case and formulate your opinion before finding out the answer!
Fungal Meningitis Outbreak
You’ve likely heard the news about the disastrous outbreak of fungal meningitis associated with the intrathecal injection of methylprednisolone acetate for adults with chronic back pain.1,2 The contaminated lots of steroid were compounded at a Massachusetts facility called the New England Compounding Center (NECC) and shipped to a wide area of the US.3 The vast majority of the more than 500 patients (including 36 deaths) in 19 states were infected with the rare fungus Exserohilum rostratum. Fungal contamination of unopened compounded drug vials was documented.2
The US Food and Drug Administration (FDA) has the authority to regulate drug manufacturing, but oversight of the compounding of specific preparations for individual patient use has fallen into a gray area between federal oversight of manufacturing and state oversight of the practice of pharmacy and medicine (thus, we have state medical licenses).3
In 2002, the US Supreme Court ruled unconstitutional a law passed by Congress to enable FDA oversight of large-scale compounding. The FDA was able to salvage many aspects of that law in its policy guide, and it appears that NECC violated some of these policies.3 This entire complex story is recounted in detail in the Nov. 22, 2012 issue of The New England Journal of Medicine3 and in two original reports in the subsequent two issues.1,2
Historical Highlights of Compounding
Originally established in 1906, the FDA has an interesting history. I recently met a very alert and healthy 82-year-old woman who was treated at Chicago’s Children’s Memorial Hospital in 1939 at the age of 8 for severe pneumococcal meningitis, and I was able to review her hospital records from that episode. She was treated with pyridine sulfanilamide and injections of rabbit type-specific pneumococcal antiserum, with an amazingly positive outcome. This is relevant because the FDA had its oversight mandate broadened in direct response to the 1937 Elixir Sulfanilamide disaster. This was the first available antibiotic to be highly effective against some infections, and it was used safely in tablet and powder form. When there was demand for a liquid formulation, the manufacturer, S.E. Massengill Co., developed a pleasant raspberry-flavored product that unfortunately used diethylene glycol, the primary ingredient in antifreeze, as a solvent. In all, there were 105 “elixir”-related deaths across 15 states. (The chemist responsible for the mixture, Harold Watkins, PhD, later committed suicide.)4
At that time, there was no legal requirement that medications be tested for toxicity, and the results were catastrophic. As a result, Congress passed the 1938 Food, Drug and Cosmetic Act, which increased the FDA’s authority to regulate drugs and required them to be safe and properly labeled. Amazingly, proof of drug efficacy was not a requirement until 1962, partly in response to the thalidomide tragedy in which a host of birth defects were linked to the drug.
Hopefully, the current tragedy will lead to tighter controls over the compounding industry, helping to safeguard patients throughout the US.
Source found here