An Assessment of biological Potency and Molecular Characteristics of Different Innovator and Noninnovator Interferon-Beta Products

Abstract

Approved innovator products and their noninnovator ‘‘copy’’ versions are likely to vary in their quality, eg, physicochemical characteristics and biological activity, with important implications for clinical efficacy and safety. Therefore, it is important to study and thoroughly evaluate the noninnovator products in comparison with approved products at the preclinical and clinical stages. We have obtained 4 noninnovator interferon (IFN)- b-1a products currently marketed in Latin America and Iran and compared these with approved IFN-b-1a products (Avonex and Rebif) obtained from the same geographical regions with respect to biological potency, estimated by in vitro bioassays, and molecular characteristics, assessed by immunoblotting and high-performance liquid chromatography. In this article, we present our data showing that the noninnovator IFN-b-1a products can vary considerably in their biological potency. In addition, we showed that all IFN-b-1a products formulated with human serum albumin contained variable amounts of higher-molecular-weight aggregates of IFN-b-1a and adducts with human serum albumin, these being more prevalent in 2 noninnovator IFN-b-1a products where biological potency was reduced compared with approved IFN-b-1a products. Additionally, significant lot-to-lot variability was observed for one of the noninnovator products. Taken together, the results of this study highlight the need for not only thorough in vitro characterization, but also preclinical and clinical assessment to ensure patient safety and efficacy.