One of the greatest challenges in drug development is performing adequate assessment of biological and microbiological risks that can compromise patient safety. Discovery of new infectious diseases, which occurs on average one to two times every year, influences how we view food and drug safety as well as hygiene.1 The measures taken to contain and evaluate the risks of bovine spongiform encephalopathy (BSE or "mad cow disease") illustrate how new risks are evaluated to determine when potential changes to regulations, practices, and disclosures to consumers are needed. The lessons apply to both the pharmaceutical and biopharmaceutical industries, where risk assessment and mitigation is a regulatory requirement.
The advent of BSE and the discovery of similar transmissible spongiform encephalopathies (TSEs) in several other animal species forced the reevaluation of risks for organ and tissue grafts, vaccines, and drugs. CJD was already known in humans-as both a spontaneously arising disease and as an iatrogenic infection from human tissues and pituitary-derived growth hormone. However, little was known about how TSEs are transmitted, diagnostic tests were not available, and conventional thinking assumed high barriers to zoonosis.2-4RELATIVE RISK Given existing knowledge and prevailing scientific opinion from 1986 to 1991, we can examine how the risks and unknowns were managed, starting with the following questions:
Prior to 2003, the regulatory bodies and TSE scientific advisory committees that assess BSE risk in different countries placed the US and Canada in an intermediate category not assumed "BSE-free."4-12,15 During 2003, officials discovered a BSE-infected animal in Canada and one in the US.18,19 In April 2004, FDA announced that — against USDA regulations — a cow with central nervous system symptoms similar to BSE was slaughtered and rendered for use in animal feed without being tested for BSE.20 The rendered protein was seized, and an ongoing investigation will determine whether it will be used solely for swine feed or destroyed.
What factors led to the emergence of BSE in North America? One hypothesis is that it developed spontaneously, independent of events in the UK. Another hypothesis suggests BSE occurs naturally in animal populations but it previously was not diagnosed.
Records show that 173 cattle imported into the US from the UK during the 1980s entered the food chain. There is a high probability that some were BSE positive.13-15
Two TSEs already existed in North America, one in deer and one in elk. Perhaps one of these TSEs crossed the species barrier, infecting cattle.