1955 – The Polio Vaccine – The Cutter Incident
On April 12, 1955, Cutter Laboratories was one of several companies that the United States government licensed to produce the Salk polio vaccine.
In what became known as the “Cutter Incident,” some lots of the Cutter vaccine (despite passing required safety tests) contained live polio virus in what was supposed to be an inactivated-virus vaccine. Cutter withdrew its vaccine from the market on April 27th after vaccine-associated cases of polio were reported. This tragedy resulted in 10 deaths and 51 children being paralyzed.
Several possible reasons for this incident were identified, including:
- An inconsistent viral inactivation process
- Quick scale-up of production without proper validation of the inactivation steps – essentially Cutter Labs was trying to meet market demands without adequate process controls and Quality Control in place.
- And a scale-up of heat inactivation step which may not have been sufficiently robust to ensure virus inactivation.
So, what GMP lessons can we learn from this?
One of the obvious solutions would have been the introduction of robust process validation particularly associated with virus inactivation. Process validation was not a formalized concept at this time, as it is today, compared with the current standards. If you are not familiar with process validation, it is defined as the collection and evaluation of data, from the process design stage throughout production, which establishes scientific evidence that a process is capable of consistently delivering quality products. Now, equipment must be qualified, and processes must be validated before drug products can be commercially distributed. The FDA published their guidance on process validation in January 2011, requiring that firms take a lifecycle approach.
As a result of this incident, The Food, Drug and Cosmetic act of 1938 was established thus giving the United States Food and Drug Administration (FDA) the authority to act and inspect manufacturing facilities. Firms were required to demonstrate that drugs were safe and must submit a New Drug Application requesting approval to commercialize the drug in the US. With the continued sporadic repeat of this event, in 2007 the FDA published guidance requiring the testing of glycerin for the presence of di-ethylene glycol.
