Abstract

Biosimilars are biotherapeutic products with similar efficacy, safety, and quality to a licensed bio-originator. Biosimilars include monoclonal antibodies, soluble receptors, growth factors, and hormones. The manufacture of biosimilars is a sophisticated multi-step process; factors at each stage, such as production cell line, culture conditions, and formulation, may each alter the final product through post-translational modifications. A vial of a therapeutic antibody contains multiple species with distinct glycosylation profiles (microheterogeneity), which are responsible, for example, for complement activation, pharmacokinetics, and structural stability. Whereas the focus for the manufacturer of the bio-originator is to show safety and efficacy in clinical trials, biosimilar development focuses predominantly on in-depth analyses to confirm that the product is identical to the originator in terms of structure, composition, and in vitro activity. Therefore, the critical quality attributes of a biological drug that influences clinical safety and efficacy should be carefully assessed. At least one clinical study is required to compare pharmacokinetics of bio-originator and biosimilar, and at least one sufficiently large randomised controlled trial to demonstrate clinical equivalence. Once biosimilarity is confirmed, regulators may allow extrapolation to other licensed bio-originator indications, provided efficacy relies on a similar mechanism of action in each one. Consequently, a biosimilar may be approved in all indications for which the bio-originator has been approved, without multiple clinical trials.