Preclinical Safety Considerations for Biosimilars

Abstract

It is now a foregone conclusion that the new frontier of biomedical research lies in biologics, which hold the potential to yield, over time, effective treatments for conditions or diseases hitherto considered incurable or untreatable. On the scale of medical development, biologics are a fairly recent innovation and the majority of them are still under patent protection. The global outlook for biologics is positive and it is estimated that approximately two-dozen biological products with global sales of more than $67 billion will come off patent by 2020. Advances in biotechnology and the end of patent exclusivity have resulted in burgeoning opportunities for cost-effective followon biologics, commonly known as ‘biosimilars’, to enter the market.

Unlike generic chemical drugs, biosimilars are similar but not identical to their respective reference innovator products. Even minor changes to the original manufacturing process may result in alterations to the secondary, tertiary, and quaternary structure of the molecule, which may have an impact on the efficacy and safety of the drug in various therapeutic indications and its safety profile in diverse risk populations may be different from that of the innovator product. The assessment of toxicity and safety of monoclonal antibodies (mAbs) becomes more challenging because of the higher complexity and size of these products, giving rise to higher variability. The manufacturing of biosimilar mAbs can lead to differences in glycosylation pattern, resulting in a high level of micro-heterogeneity. In addition, mAbs often have a complex mode of action as they comprise multifunctional molecules with biological properties involving both their Fab and Fc fragments. Many challenges are associated with the approval process of biosimilar mAbs. Read More...