The registration of follow-on biologics will depend on the availability of data demonstrating comparability with a reference product. It is recognised that measurement of relative immunogenicity will be an important component of the product comparability assessment. The way in which this is done will depend on a multidimensional risk-based approach that considers the probability of generating an immune response relative to the consequences of such a response. This paper presents principles and practical guidance for constructing a risk assessment, building on the experience gained for a variety of biopharmaceutical products. This includes the use of preclinical models and validated bioanalytical methods. Ultimately, post-marketing monitoring will be required to evaluate more fully the risk in representative settings, given the multifactorial nature of the potential immunogenicity of different therapeutic proteins.
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