Changes in biological source material

A change in source (or raw) material can be radical, e.g. changing the derivation of a therapeutic protein from human plasma to recombinant DNA manufacture, or the change may be more subtle, e.g. the change from a non-inactivated bovine serum growth supplement to an inactivated serum. The former type of change is usually driven by manufacturing strategy and has vast consequences for the regulation of the product concerned. The latter type of change is usually driven by a need to increase the assurance of viral safety and the regulatory implications for the product are significantly less severe. In this latter example, inadvertent alterations to the product may result from changes in cell metabolism brought about by the change in its growth conditions and these need to be addressed in comparability studies. Ultimately, the implication of any slight change in the fine structure of a biotech medicinal product on its efficacy and/or immunogenicity will have to be dealt with on a case-by-case basis.