Small-Angle X-ray Scattering as a Powerful Tool for Phase and Crystallinity Assessment of Monoclonal Antibody Crystallites in Support of Batch Crystallization

• DOI: 10.1021/acs.molpharmaceut.4c00418
• Publication Date: 2024-07-03T13:24:46Z
• Authors: Patrick Larpent; Lorenzo Codan; Jameson R. Bothe; Luca Iuzzolino; Suzette Pabit; Sudipta Gupta; Thierry Fischmann; Yongchao Su; Paul Reichert; Dirk Stueber; Aaron Cote
• Keywords: Small-angle X-ray scattering; Wide-angle X-ray scattering

Crystalline suspensions of monoclonal antibodies (mAbs) have great potential to improve drug substance isolation and purification on a large scale be used for delivery via high-concentration formulations. mAb are expected enhanced chemical physical properties relative solutions delivered intravenously, making them attractive candidates subcutaneous delivery. In contrast small molecules, the development protein crystalline is not widely approach in pharmaceutical industry. This mainly due challenges finding hits suboptimal resulting crystallites when found. Modern advances instrumentation increased knowledge crystallization have, however, resulted higher probabilities discovering crystal forms improving their particle characterization. this regard, physical, analytical characterization plays central role initial steps understanding later optimizing mAbs requires careful selection appropriate tools. contribution describes novel structure antibody pembrolizumab demonstrates usefulness small-angle X-ray scattering (SAXS) characterizing its suspensions. It illustrates advantages SAXS (i) confirm crystallinity phase produced batch mode; (ii) under various conditions detect variations phases, enabling fine-tuning crystallizations control across multiple batches; (iii) monitor response stability suspension with regard filtration washing; (iv) upon drying. Overall, work highlights how an essential tool