In vitro Adventitious Virus Assays
Manufacturers of biopharmaceutical products derived from cell lines of human or animal origin are required to test their products at appropriate stages of production for the absence of contaminating infectious viruses. Such testing is required on master cell banks, working cell banks, cells at the limit of in vitro cell age, and unprocessed bulk harvest material. Similar testing is also required for virus vector and vaccine seed stocks, although there may be difficulties in detecting contaminating viruses in the presence of a live virus vector, and a customised approach to testing may be required for such products. (ICH Q5A; FDA PTC 1993; Ph.Eur. 2.6.16).

In vitro assays involve inoculating a test sample onto various indicator cell lines, capable of detecting a wide range of human and relevant animal viruses. The choice of indicator cell lines depends on the species of origin of the cell bank to be tested (or cell line used to produce the virus/vector), as well as the history of the cell line, and should reflect the virus contaminants that could possibly be present. In general, a minimum of three cell lines is required, including a human diploid cell line, a monkey kidney cell line, and a cell line of the same species and tissue type as that used in the production of the manufacturers’ product. The assays are designed to detect both cytopathic and haemadsorbing viruses.

The following validated in vitro assays for the characterisation of products derived from rodent or human cell lines are available.

• 14 day invitro assays using a customised combination of cell lines MRC-5, Vero, CHO-K1, HeLa, HEK293, Murine, etc.
• 28 day invitro assays using a customised combination of cell lines MRC-5, Vero, CHO-K1, HeLa, HEK293, Murine, etc.

Indicator lines suitable for use in the testing of other products, or to extend the host range of the indicator panel, may be available on request. We are able to design complex and customised assays to meet specific product requirements.

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