Center for Structural Biology and Bioinformatics, Laboratory for the Structure and Function of Biological Membranes, Campus Plaine CP206/02, Université Libre de Bruxelles, B1050 Brussels, Belgium.
Int J Mol Sci. 2022 Oct 7;23(19):11895. doi: 10.3390/ijms231911895.
Quality control of drug products is of paramount importance in the pharmaceutical world. It ensures product safety, efficiency, and consistency. In the case of complex biomolecules such as therapeutic proteins, small variations in bioprocess parameters can induce substantial variations in terms of structure, impacting the drug product quality. Conditions for obtaining highly reproducible grafting of 11-mercaptoundecanoic acid were determined. On that basis, we developed an easy-to-use, cost effective, and timesaving biosensor based on ATR-FTIR spectroscopy able to detect immunoglobulins during their production. A germanium crystal, used as an internal reflection element (IRE) for FTIR spectroscopy, was covalently coated with immunoglobulin-binding proteins. This thereby functionalized surface could bind only immunoglobulins present in complex media such as culture media or biopharmaceutical products. The potential subsequent analysis of their structure by ATR-FTIR spectroscopy makes this biosensor a powerful tool to monitor the production of biotherapeutics and assess important critical quality attributes (CQAs) such as high-order structure and aggregation level.
药品质量控制在制药领域至关重要。它确保了产品的安全性、效率和一致性。在治疗蛋白等复杂生物分子的情况下，生物工艺参数的微小变化会导致结构发生实质性变化，从而影响药物产品的质量。确定了获得 11-巯基十一酸高重现性接枝的条件。在此基础上，我们开发了一种基于衰减全反射傅里叶变换红外光谱（ATR-FTIR）的简单、经济高效且省时的生物传感器，能够在生产过程中检测免疫球蛋白。将免疫球蛋白结合蛋白共价涂覆在用作 FTIR 光谱内反射元件（IRE）的锗晶体上。因此，功能化表面只能结合复杂介质（如培养基或生物制药产品）中存在的免疫球蛋白。ATR-FTIR 光谱对其结构的潜在后续分析使这种生物传感器成为监测生物治疗药物生产和评估重要关键质量属性（CQAs）的有力工具，如高级结构和聚集水平。
