Immunogenicity of locally acting large molecule products: An overview.

Locally acting large molecule drug products, including biologics, are designed for site-specific pharmacological action with minimal systemic exposure. Immunogenicity is generally assessed to the same extent in the clinical development programs for these locally acting large molecule drug products as for biological products given systemically. However, it is uncertain whether the local route of administration bears the same clinical immunogenicity concerns relative to systemic administration. This overview examines the immunogenic potential of locally acting large molecules, summarizing the anti-drug antibody incidence and its impact on pharmacokinetics, safety, and efficacy, and highlighting the specific immunogenicity risk profiles for these locally acting drugs and biologics.