The approach used to establish the safety of veterinary vaccines produced in the BHK 21 cell line.

A unique feature of the BHK 21 system is that the hamster provides a readily available and extremely sensitive (5, 13) assay system for process validation assays (Table IV outlines a production control scheme) since only between 5 and 100 cells are needed for tumors to form. While it was argued on theoretical grounds that a transforming agent active in a target species would not necessarily induce transformation in hamsters, clinical evidence has shown that the tumorigenicity of BHK 21 cells is a whole cell phenomenon. The main points to be drawn from the work with BHK 21/13 cells are as follows: 1. Cell culture technology now allows standardized, safe, effective, economical, large-scale vaccine production. 2. Although intact BHK 21 cells have been shown to be tumorigenic in hamsters, which is the species of origin for the cell line, no tumorigenic activity has been demonstrated in a variety of other aspects. 3. Even in hamsters, BHK 21 cells must be intact to cause tumor growth, a condition which can easily be avoided in biologicals production. 4. Decisions on the acceptability of a cell like the BHK 21 line were made on the basis of multiple species studies and validation of the manufacturing process to show that the final product was free of biologically active contaminants.