Development of new analytical tools is a key opportunity for innovation amongst biopharmaceutical researchers. In this case study, we describe novel methods for analysis of critical quality attributes of a follow-on biologic product. A reverse phase ultra performance liquid chromatography (RP-UPLC) method is described, which is used to analyze content, potency, and related protein impurities. As compared to an existing high performance liquid chromatography (HPLC) method, the RP-UPLC method features improved robustness and leverages a smaller particle size in the stationary phase to obtain a greater separation efficiency, while also achieving a lower limit of quantitation. We also describe an improved high performance size exclusion chromatography (HP-SEC) method for determination of high molecular weight proteins for the same follow-on biologic. Furthermore, we present an approach that was employed successfully to establish equivalency of these methods to the methods described in product-specific compendial monographs. An increasing number of mature biopharmaceutical products have official compendial monographs, such as those published by the United States Pharmacopeia, which provide the acceptable limits for quality attributes and describe the analytical methods used to measure these attributes. Often, compendial monograph methods are provided by the innovator, and at the time of monograph elaboration these methods may no longer represent state-of-the-art analytical technology. Pharmacopeia allow for equivalent alternate methods to be used, but do not specify the exact requirements for demonstrating equivalence. In this case study, we present the methodology that was successfully used to establish equivalence between improved RP-UPLC and HP-SEC methods and the corresponding monograph methods for a follow-on biologic. The methods described will be of interest to biologics researchers, and the method equivalence strategy provides a roadmap for researchers seeking to introduce alternate or superior analytical methods for any biopharmaceutical drug product with an elaborated monograph. 

Improved analytical methods for a follow-on biologic: Method development and strategy to establish equivalency to monograph methods

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

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