DRUG DEVELOPMENT Immunogenicity: anticipating and avoiding issues for biopharmaceutical development

an immune response in the recipient: this may be the intended effect, as in the case of vaccines, or unintended. Depending on the nature and magnitude of the response, unintended immunogenicity can impact negatively on overall clinical benefit and risk. All biopharmaceutical products have an intrinsic immunogenic potential by virtue of molecular features that can stimulate cells of the adaptive and innate immune systems. However, this does not imply that immunogenicity will have a negative influence on treatment outcome – rather, the challenge for the regulator is to understand the scale of the immune response in relation to risk of adverse events and/or reduced efficacy for the population to be treated. Accordingly, the critical question to address for developability and approvability is whether manifestations of an unintended immune response to the drug product are of a sufficient scale – taking into account the rate of occurrence and the severity of consequences – to affect the overall clinical benefit and risk balance. In the vast majority of cases, unintended immunogenicity does not represent a roadblock for successful clinical development and registration. Moreover, sponsors can effectively de-risk biopharmaceutical development by anticipating and mitigating immunogenicity-related risks.