Immunogenicity Assessment of Biosimilars

Biosimilar versions of original therapeutic proteins and peptides are approved on the basis of an extensive demonstration of analytical similarity to the originator product, including in-vitro tests for function. Comparative clinical evaluation is also performed in the pre-authorisation phase to confirm that the analytical similarity has led to comparable safety and efficacy, including immunogenicity. This article reviews the regulatory standards applicable to the assessment of relative immunogenicity of biosimilar candidates for marketing authorisation in the European Union and USA. The most critical elements for the design of an effective product-specific strategy to exclude potential incremental immunogenicity are discussed, and case examples are presented to illustrate how data are assessed by regulatory authorities.