Human retroviruses and herpesviruses: problems and solutions in safety testing of biologicals.

Contamination by retroviruses and herpesviruses is a major concern when evaluating the safety of biological products, particularly when human cell or human-derived products are used. Both virus groups are associated with oncogenic disease, and other serious immunosuppressive or degenerative conditions. Their capacity to remain as latent infections within the cell enhances the concerns in safety testing. A testing regime must take account of the known human retroviruses and herpesviruses, unknown or variant viruses and the possibility that recombinants or pseudotypes can be formed between human and animal retroviruses. To cover these possibilities the Master Cell Bank and Manufacturer's Working Cell Bank should be screened by DNA hybridisation for known viruses. At each stage of the production process culture techniques should be utilised to detect known and variant viruses which might not be detected by hybridisation. PCR has a particular value in screening the final product but this technique requires rigorous quality control procedures.