Concerns about the economic viability of biosimilars center on their high development cost relative to small-molecule generics, along with (and partly because of) the difficulty in demonstrating bioequivalence for these complex molecules. Immunogenicity is a particular area of increasing vigilance at both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) (1, 2). Unwanted immunogenicity is an underlying cause of multiple deleterious effects for all protein-based therapeutics — including loss of efficacy, altered pharmacokinetics, and reduced stability (3,4,5,6,7,8) — and it poses a major risk for product failures and recalls.
Failure to demonstrate equivalent or (ideally) lower immunogenicity for a biosimilar is both costly and risky. Development of an unsatisfactory or inconsistent immunogenicity profile during development — or much worse, during postmarket surveillance — may be economically disastrous. It can even lead to costly reformulation work and additional clinical studies. Complicating the problem further, immunogenicity may sometimes arise only after repeated administration over an extended period. So it is imperative that all potential sources of unwanted immunogenicity be dealt with stringently as part of a risk-management plan during development to ensure a predictable, stable, and acceptable immunogenicity profile during manufacturing and storage through lot expiry.