Concerns about BSE contamination of pharmaceuticals became serious in the early 1990s when the first cases of vCJD were discovered.
At one point, the European Parliament considered banning the use of all raw materials derived from animals. At the time, more
than 90% of approved pharmaceuticals contained such materials, notably gelatin and stearate derivatives. To remove these pharmaceuticals
from use without a single case of transmission to humans appeared excessively cautious. Instead, regulators issued guidance
documents urging firms to evaluate animal-derived raw materials for suitability and safety, and a list of high-risk tissues
was developed.5-12
Many firms devoted significant process-development resources to replacing high-risk, animal-derived raw materials with items
perceived to be safer. Serum, serum-derived proteins, even tallow-derived compounds (such as polysorbate 80, glycerol, and
stearates), and bovine insulin (replaced with recombinant insulin produced in bacteria), were replaced in many pharmaceutical
products.
For biological products, such as vaccines or proteins produced in cell culture, a clear distinction is made between one-time
risks and recurrent additive risks.8,9
One-time risks include the exposure of the original master cell bank to serum or other raw materials, while repeated risks
involve using specified risk materials in each production lot. Based on the current data, blood and blood-derived products,
although a potential concern, appear lower in risk than human organs or tissues for CJD and probably for vCJD as well. To
date only one person has developed vCJD after exposure to donor blood of a person who later developed vCJD.30
It cannot be determined whether the transfusion caused the infection.
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The risk of TSEs in pharmaceuticals is thought to lie in the use of high-risk, animal-derived raw materials, such as brain,
spinal cord, and some other organs. These raw materials have been used as excipients, starting materials, or in-process materials
that are not present in the final product.29-31
Accordingly, the industry has been mandated since the 1990s to reduce or eliminate exposure to high-risk materials. Risk
is assessed according to an animal's country of origin, tissue or organ sourced, and the proximity of the raw material to
the patient.31
Table 2 lists some of the most commonly used raw materials and excipients in the pharmaceutical industry, and their relative
TSE risk as currently understood.4-12 Ruminants and primates are the highest-risk species, while TSEs have not been detected in poultry and pigs, so they are
assumed to be safer. Brain and spinal cord tissue has the highest risk, based on tissue infection studies. Country of origin
of the animals is another key risk factor having four categories, ranging from no BSE detected (not necessarily BSE-free),
low incidence of BSE suspected, low incidence of BSE known, and highly infected with BSE. Sourcing raw materials from low-risk
countries is one approach to reducing BSE risk. As the recent cases of BSE in North America do not significantly change the
risk classification of the US or Canada, little direct impact is expected on most pharmaceutical products at this time. However,
dietary supplements made using high-risk tissue such as bovine brains could be greatly affected. Similarly, firms with mature
product lines, especially certain vaccines that require high-risk materials for growth, may have more serious regulatory concerns.
Substituting complex, biologically active raw materials for "safer" materials may affect product quality and it requires significant
process development. Relying on sourcing from a "safer" country of origin also can be risky, as the status of a country may
change at any time and supplies are limited.
In contrast to the conservative steps applied to pharmaceutical products, dietary supplements were not placed under similar
regulation until February 2004.
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