Analytical Method Validation for Biopharmaceuticals

Method validation has a long and productive history in the pharmaceutical and now, biopharmaceutical industries, but it is an evolving discipline which changes with the times. Though much has been written about method validation for conventional, small molecule (SM) pharmaceuticals, less has appeared providing an overview of its application for complex, high molecular weight (MW) biopharmaceuticals (or biotechnology) products. This appears to be satisfyingly changing with the times, and this particular chapter has been designed to address this area of method validation. We hope to address herein the important issues of where do analytical method validation guidelines and directives stand today for biopharmaceutical (protein or related) products. Due to the recognized differences and complexity of biopharmaceuticals relative to small molecule drugs, regulatory agencies have accepted that what is expected of all SM, single molecule entities (even enantiomers), cannot be required for complex protein biopharmaceuticals, such as antibodies. While it is quite a simple matter, in most instances, to characterize and validate methods for SM drug substances, this is not always the case for complex biopharmaceuticals. Biotechnology products will always be heterogeneous mixtures of product-related species.