Analytic characterization of biosimilars.

Purpose: The biosimilar development process, comparability for biological agents, and analytic characterization of biosimilars are described.

Summary: Healthcare providers must understand the requirements for biosimilar approval, including the science behind biosimilar development and testing that contributes to the totality of evidence. The foundation of development is to demonstrate that a biosimilar is highly similar to the reference product through analytic characterization. Advances in analytic techniques enable scientists to extensively characterize biological products to identify potential product differences compared with the reference product that may affect the purity, safety, and efficacy of the biosimilar candidate. When developing a biosimilar, the clinical efficacy of the biological product has been proven with trials from the reference biological product; therefore, analytic testing on the molecular structure and biological function becomes the focus. In addition, nonclinical studies in animals are performed, including toxicology and immunogenicity testing. In humans, clinical pharmacology studies are performed to evaluate the safety and the pharmacokinetic and pharmacodynamic properties of the proposed biosimilar. If there is any residual uncertainty about the proposed biological product after this testing, the developer should use guidance from the Food and Drug Administration to determine what additional clinical studies may be needed to adequately address that uncertainty.

Conclusion: Requirements for the approval of a biosimilar product include analytic characterization, which tests for similarity in primary amino acid structure, analysis of higher-order structure using circular dichroism and nuclear magnetic resonance spectroscopies, detection of posttranslational modifications, assessment of optimal target binding, and testing for impurities and optimal potency.