"I. Introduction
We, FDA, are providing you, manufacturers of viral vaccines, guidance for the characterization and qualification of cell substrates, viral seeds, and other biological materials used for the production of viral vaccines for human use...
III. Characterization and Qualification of Cell Substrates, Viral Seeds, Biological Raw Materials and Vaccine Intermediates
... The regulations, in 21 CFR 610.13, state in part that 'Products shall be free of extraneous material except that which is unavoidable in the manufacturing process described in the approved biologics license application.' In 21 CFR 600.3(r), purity is defined as the 'relative freedom from extraneous matter in the finished product, whether or not harmful to the recipient or deleterious to the product'...
IV. Description of Test Methods
The tests described in this Section may be used to address the considerations discussed in Section III. Advances in science and technology are likely to yield additional information that could lead to modification or replacement of some of these tests, and except where prohibited by regulation, manufacturers may use alternative test methods, where scientifically justified. Manufacturers should consider how they can replace, refine, or reduce their use of in vivo tests...
2. Testing for Residual Cellular DNA: ... Residual DNA might be a risk to your final product because of oncogenic and/or infectivity potential. There are several potential mechanisms by which residual DNA could be oncogenic, including the integration and expression of encoded oncogenes or insertional mutagenesis following DNA integration. Residual DNA also might be capable of transmitting viral infections if retroviral proviruses, integrated copies of DNA viruses, or extrachromosomal genomes are present."