Higher order structure of proteins in biopharmaceutical development

The higher order structure (HOS) of proteins is important to characterize and understand during the process of biologic drug development. Although a wide range of analytical techniques is used for HOS characterization, there are no public guidelines or best practices for the application of physicochemical techniques to characterize specific HOS properties. The timing is now advantageous for developing guidelines or best practices that would facilitate the development and characterization of biologics. These guidelines would inform research and development efforts, promote process understanding, and ensure drug product quality. To this end, in December 2016, U.S. Pharmacopeia (USP) hosted a roundtable attended by invited scientists and regulators with expertise in HOS techniques and applications. As participants in this roundtable, we discussed many practical issues and raised questions for further consideration. We reached consensus on the current applications, strengths, and weaknesses of many of the analytical techniques for HOS characterization (Table 1). USP, especially through its informational chapters, is uniquely positioned to facilitate these efforts as an independent, scientific, nonprofit standardssetting organization. Comments, suggestions, and opinions are actively sought from all stakeholders on the content expressed here, and on the appropriate next steps as we seek to make the analysis of HOS more consistent in practice and the results more definitive, so that more meaningful comparisons across labs and molecules can occur.