Guidance on Immunogenicity Assessment and Testing (FDA & EMA)

 Immune responses to therapeutic protein products may pose problems for both patient safety and product efficacy. Immunologically based adverse events, such as anaphylaxis, cytokine release syndrome, and cross-reactive neutralization of endogenous proteins mediating critical functions, have caused sponsors to terminate the development of what otherwise may have been efficacious therapeutic protein products. Unwanted immune responses to therapeutic protein products may also neutralize their biological activities and result in adverse events not only by inhibiting the efficacy of the therapeutic protein product but also by cross-reacting to an endogenous protein counterpart, leading to loss of its physiological function (e.g., neutralizing antibodies to therapeutic erythropoietin cause pure red cell aplasia by also neutralizing the endogenous protein). 

The regulatory agencies including FDA& EMA have outlined and recommended the risk-based approach to evaluating and mitigating immune responses to or adverse immunologically related responses associated with therapeutic protein products that affect their safety and efficacy. The sponsors are recommended to follow these guidelines while developing immunogenicity assessment strategies and assays. Details can be found at 

Food and Drug Administration Guidance:

• Immunogenicity Assessment for Therapeutic Protein Products
• Immunogenicity Testing of Therapeutic Protein Products — Developing and Validating Assays for Anti-Drug Antibody Detection

EMA Guidelines

• Guideline on Immunogenicity assessment of therapeutic proteins