The end product, along with all contaminants, must be analyzed and detailed specifications set before it can be released under controlled conditions. The biological product is thus defined more by the process than the final analysis. The combination of process control and final analysis is the only way FDA and the manufacturer can be assured that a product is sterile, pure, potent, and stable, and still function in precisely the same way it did in pivotal trials. For recombinant products, CBER requires the same control of source material and final product purity, identity, and sterility. In this case, control starts at the level of the Master Cell Bank, as long as all details of the gene insert, cell banking, and adventitious agent identification have been provided.
Control continues through the manufacturing process.
The frequency with which manufacturers send partially processed drug intermediates from place to place before cGMPs apply is unknown in the biologics world. However, recombinant protein technology can deliver high concentrations of an ultra pure final drug substance. While the drug substance remains a population of closely related molecules, the precision with which it can be characterized approaches that of drugs. This Guidance allows for increased reliance on biochemical and biophysical characterization of the final drug substance to test the effects of changes in process, scale, or even manufacturing site. The less comparable the new and old product, the more likely animal or human testing of the new drug product would be needed to demonstrate that the new and old product are essentially the same.