Module 9 2024

03/09/2024

Immunogenicity Assessment

• With the exception of vaccines, the immunogenicity of a biological product is potentially an undesirable attribute

• All therapeutic proteins, even those that share a common structure sequence with endogenous human proteins have an intrinsic potential to induce undesirable immunogenicity in human subjects. • Potential clinical consequences of an unwanted immune response include loss of efficacy, serious acute immune effects such as anaphylaxis. evaluated in the context of its potential or actual impact on both product potency and safety in preclinical and clinical studies • Subtle changes in product quality can have far reaching immunological effects which might (and in some cases have) radically alter the benefit/risk balance adversely • It must be fully characterised and its consequences

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Immunogenicity Lessons Learned

• First therapeutic insulins products in the 1920s were of bovine/porcine origin – leading to fatal anaphylactic reactions. Linked to other contaminating proteins. • Human growth hormone (hGH) derived from pituitary glands of cadavers used to treat children suffering from hypopituitary. For the early products, 50% children developed immune reaction – risk lowered by removing significant presence of aggregated hGH • Humanization of monoclonal antibodies has significantly decreased immunogenicity risk, observed with early murine antibodies. • Patients treated with early gene therapy products suffered severe immune reactions to the viral vector (Gene’s Delivery Vehicle)

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