Comparative testing and pharmacovigilance of biosimilars.

Unlike traditional generic pharmaceuticals, biosimilars (also called 'follow-on biopharmaceuticals' in the USA) aim to copy a complex recombinant, three-dimensional protein structure with high molecular weight. Small changes in the manufacturing process can alter the product's effect and safety. According to the guidelines of the European Agency for the Evaluation of Medicinal products (EMEA), extensive comparability testing will be required to demonstrate that the biosimilar has a comparable profile in terms of quality, safety and efficacy as the reference product. Various analytical assays are available to compare physicochemical and biological properties between production batches of a potentially similar biopharmaceutical (comparability) and in comparison with a reference product (similarity). It is important to recognize the limits of existing assays so that the results can be accurately interpreted for market authorization. This article examines the quality and limits of such analytical methods. The analytical tests to demonstrate comparability and similarity of a biosimilar product to a reference drug with respect to protein content, activity, physiochemical integrity, stability, impurities and additives, as well as immunogenicity are discussed. Although several assays are available, reliable tests for safety and efficacy still require development. Furthermore, international standards are missing and materials and methods differ from laboratories making the comparison of results very difficult. Clinical trials and post-authorization pharmacovigilance are essential to guarantee the product's safety and efficacy over time. Pharmacovigilance, as part of a comprehensive risk management programme, will need to include regular testing for consistent manufacturing of the drug.