'The working cell bank as a starting cell substrate for drug production should be tested for adventitious viruses either by direct testing or by analysis of cells at the limit of in vitro cell age, initiated from the WCB. When appropriate non-endogenous virus tests have been performed on the MCB and cells cultured up to or beyond the limit of in vitro age have been derived from the WCB and used for testing for the presence of adventitious viruses, similar tests need not to be performed on the initial WCB. Antibody production tests (MAP, RAP, or HAP) are usually not necessary for the WCB. An alternative approach in which full tests are carried out on the WCB rather than on the MCB would also be acceptable. ' 'The limit of in vitro cell age used for production should be based on data derived from production cells expanded under pilot-plant scale or commercial-scale conditions to the proposed in vitro cell age or beyond. Generally, the production cells are obtained by expansion of the WCB; the MCB could also be used to prepare the production cells. Cells at the limit of in vitro cell age should be evaluated once for those endogenous viruses that may have been undetected in the MCB and WCB. The performance of suitable tests (e.g. in vitro and in vivo) at least once on cells at the limit of in vitro cell age used for production would provide further assurance that the production process is not prone to contamination by adventitious virus. If any adventitious viruses are detected at this level, the process should be carefully checked in order to determine the cause of the contamination, and completely redesigned if necessary.'