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 1986 discovery of BSE in the UK — a previously unknown disease in cattle — set off a chain of events that continues to
affect the food and drug industries.2-12 Despite efforts to impose feeding bans, limit exports from the UK, and destroy at least four million diseased cattle, BSE
prevalence continued to grow for years after protective measures were implemented (see Table 1).13,14 At the peak of the UK BSE epidemic, about 1,000 infected cattle were detected each week. BSE has since appeared in about
30 countries, apparently spread by UK cattle or feed.13,15
In 1994, a new disease, variant Creutzfeld-Jakob disease (vCJD), appeared in humans.16,17 vCJD likely was caused by a cross-species infection, or zoonosis, from BSE-infected cattle parts that entered the human
food chain. It is thought that BSE itself originated from a similar transfer of scrapie infection from goats and sheep to
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.2-4
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:
- What safeguards were appropriate to control BSE incidence in cattle before the first known case of human vCJD?
- What government controls on food are needed after a very rare food-borne risk is identified?
- How do we decide whether raw materials derived from the same animals pose a safety risk when used to manufacture pharmaceuticals?
- How safe is safe enough for food? And for drugs?
- How central a concern is BSE, or vCJD, for food and drug consumers?
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
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,