Back to In Vivo Testing

The 1993 Points to Consider in the 'Characterization of Cell Lines Used to Produce Biologicals' (FDA/CBER 1993) guideline notes that human epithelial cell lines and all cells used for live virus vaccine production should be tested for tumorigenicity. Moreover, some special cases that involve somatic cell or gene therapy products could also require tumorigenicity testing. In contrast, rodent cells need not be tested for tumorigenicity because virtually all continuous cell lines of rodent origin have been shown to be tumorigenic. Using the in vivo testing model can assess tumorigenic potential of a cell line. Several in vivo systems are used for tumorigenicity testing, according to the 1993 PTC: BioReliance uses the nude mice model for the in vivo tumorigenicity testing. The International Committee on Harmonization (ICH) guideline Q5D, 'Derivation and Characterization of Cell Substrates Used for Production of Biotechnological / Biological Products', also requires tumorigenicity testing for products for which the presence of live cells cannot be excluded or products that have little downstream purification (e.g., conventional live virus vaccines). For highly purified products that contain no cells, tumorigenicity testing may not be necessary, provided that residual host cell DNA limits are established and met by process validation studies or lot release testing. Similarly to 1993 PTC, the ICH guideline Q5D does not require tumorigenicity testing for cell lines that have previously been shown to be tumorigenic. However, new or previously uncharacterized diploid cell lines should be evaluated for their tumorigenic potential by using cells from the master cell bank (MCB).