Emerging Analytical Technologies for Biotherapeutics Development

LEVEL: INTERMEDIATE A major goal of pharmaceutical development is to characterize pathways of chemical and physical instability and then to develop strategies to minimize them. Deamidation and oxidation are examples of the former, aggregation a result of the latter. The potential for the presence of multiple variants in protein-based pharmaceuticals highlights a need for analytical methods capable of reliably and accurately identifying and measuring those variants. The ideal analytical method would be sensitive, accurate, linear over a broad range, resistant to sample-matrix interference, capable of measuring all possible structural variants of a protein, and would allow for high throughput. Needless to say, such a method does not yet exist. So multiple methods are used to study the different characteristics of each protein. Chromatography and electrophoretic techniques have traditionally been the analytical “work horses” for measuring and monitoring protein quality. They are used in all stages of research and development including formulation development, comparability assessment, and commercial-product quality testing (release and stability). Although several of these methods have long been common in biotechnology product development, motivation for continued advancement stems from the desire to improve their sensitivity, accuracy, and specificity and adapt them to changing sample characteristics (e.g., highconcentration formulations) as well as higher throughput. We focus here on methods to detect, measure, and/or characterize protein aggregates and particles as well as advances in highthroughput technologies.