Evaluation of the human host range of bovine and porcine viruses that may contaminate bovine serum and porcine trypsin used in the manufacture of biological products

Abstract

Current U.S. requirements for testing cell substrates used in production of human biological products for contamination with bovine and porcine viruses are U.S. Department of Agriculture (USDA) 9CFR tests for bovine serum or porcine trypsin. 9CFR requires testing of bovine serum for seven specific viruses in six families (immunofluorescence) and at least 2 additional families non-specifically (cytopathicity and hemadsorption). 9CFR testing of porcine trypsin is for porcine parvovirus. Recent contaminations suggest these tests may not be sufficient. Assay sensitivity was not the issue for these contaminations that were caused by viruses/virus families not represented in the 9CFR screen. A detailed literature search was undertaken to determine which viruses that infect cattle or swine or bovine or porcine cells in culture also have human host range [ability to infect humans or human cells in culture] and to predict their detection by the currently used 9CFR procedures. There are more viruses of potential risk to biological products manufactured using bovine or porcine raw materials than are likely to be detected by 9CFR testing procedures; even within families, not all members would necessarily be detected. Testing gaps and alternative methodologies should be evaluated to continue to ensure safe, high quality human biologicals.

Cell substrates for the production of viral vaccines

“…serum from bovines, trypsin from pigs, etc. [43,44]). The European Commission published a guidance that applied to any material derived from "transmissible spongiform encephalopathy (TSE) relevant animal species", which are used for the preparation of raw and starting materials required for production, including those used to prepare WCB or new MCB [45].…”

The Art of Animal Cell Culture for Virus Isolation

“…A recent compilation of bovine and porcine viruses that may contaminate bovine serum and porcine trypsin is available in ref. 59. As new viruses are discovered, awareness of their possible presence in biologicals like sera and trypsin draws more interest and attention.…”

DsbA-DsbAmut fusion chaperon improved soluble expression of human trypsinogen-1 in Escherichia coli

“…To date, the trypsin used in the lab and industry is mostly extracted from the pancreas of Bos taurus or domesticated swine. However, donor organism might inevitably carry some pathogenic microorganisms [2] which might be left in the subsequent products and greatly increase the potential risk, especially for medicinal field. Thus, biosynthetic trypsin is in urgent need to circumvent this risk by developing a mature approach to obtain trypsin with high safety and quality.…”