Using X-Ray Crystallography to Simplify and Accelerate Biologics Drug Development
Abstract
Every major biopharmaceutical company incorporates a protein crystallography unit that is central to its structure-based drug discovery efforts. Yet these capabilities are rarely leveraged toward the formal higher order structural characterization that is so challenging but integral to large-scale biologics manufacturing. Although the biotech industry laments the shortcomings of its favored biophysical techniques, x-ray crystallography is not even considered for drug development. Why not? We suggest that this is due, at least in part, to outdated thinking (for a recent industry-wide survey, see Gabrielson JP, Weiss IV WF. Technical decision-making with higher order structure data: starting a new dialogue. J Pharm Sci. 2015;104(4):1240-1245). We examine some myths surrounding protein crystallography and highlight the inherent properties of protein crystals (molecular identity, biochemical purity, conformational uniformity, and macromolecular crowding) as having practicable commonalities with today's patient-focused liquid drug products. In the new millennium, protein crystallography has become essentially a routine analytical test. Its application may aid the identification of better candidate molecules that are more amenable to high-concentration processing, formulation, and analysis thereby helping to make biologics drug development quicker, simpler, and cheaper.
Department
Molecular, Cellular and Biomedical Sciences
Publication Date
2-1-2017
Journal Title
Journal of Pharmaceutical Sciences
Publisher
Elsevier
Digital Object Identifier (DOI)
Document Type
Article
Recommended Citation
Brader ML, Baker EN, Dunn MF, Laue TM, Carpenter JF (2017) “Using X-ray Crystallography to Simplify and Accelerate Biologics Drug Development” J. Pharm. Sci 106:477-494.