Approval Standards for Alfa Interferon Subtypes

Abstract

The quality and potency of recombinant proteins is peculiarly dependent on numerous factors in the manufacturing process. The producing strain, the plasmid, and the production process from fermentation to final purification have a profound influence on the impurities in the drug substance as well as on the structure of the compound, particularly its tertiary structure, which has implications for receptor-binding, mechanism of action and, ultimately, clinical safety and eflcacy. The molecule produced from a defined strain and process must also be fully characterized to determine whether impurities or compounds related to the encoded protein may be present that can affect quality, safety, efficacy, and antigenicity. Even when a new product meets specifications comparable to those of an approved reference product, however; the active substance and the profile of impurities will probably differ since both the nature of the active substance and the impurity profile are process-dependent. Since many variables can affect biologic activity as well as clinical safety and eflcacy, controlled clinical trials must be conducted to establish safety and efficacy. This review describes scientific issues regarding production, characterization, quality assurance, biologic activity, and clinical safety and efficacy, which relate specifically to recombinant alfa interferons but also have broader application for approval standards for other recombinant proteins produced by a new manufacturer using a completely different manufacturing process.