Cao S, Jiao N, Jiang Y, Mire-Sluis A, Narhi L O
Process and Product Development, Thousand Oaks, CA 91320, U.S.A.
Pharmeur Bio Sci Notes. 2009 Oct;2009(1):73-9.
Biologics represent a large and growing segment of the therapeutic medicinal market. Sub-visible particles present in these products are a product quality attribute and a potential patient safety concern yet to be fully explored. Early and consistent particle quantitation and control throughout the product life cycle of these drugs from development to commercial lot release is critical in mitigating any concerns. This requires appropriate analytical methods which can be applied to biopharmaceuticals across a large variety of protein concentrations and modes of administration. The compendial light obscuration method for quantitating sub-visible particles in small volume parenterals is not ideally suited for therapeutic biologics. Approaches to modify the current compendial method so that it is applicable to biologics, including appropriate sample preparation, reduced assay sample volume, increased sizing information, and development of an appropriate sampling plan, are presented in this article. Successful applications of a modified light obscuration method to therapeutic protein products are demonstrated, and a strategy to utilise complimentary methods and techniques at different phases of product development is discussed.
生物制品在治疗性药物市场中占据着很大且不断增长的份额。这些产品中存在的亚可见颗粒是一种产品质量属性，也是一个尚未得到充分探索的潜在患者安全问题。在这些药物从研发到商业批量放行的整个产品生命周期中，尽早且持续地进行颗粒定量和控制对于缓解任何担忧至关重要。这需要合适的分析方法，这些方法可应用于各种蛋白质浓度和给药方式的生物制药产品。用于定量小容量注射剂中亚可见颗粒的药典光阻法并不完全适用于治疗性生物制品。本文介绍了修改当前药典方法以使其适用于生物制品的方法，包括适当的样品制备、减少测定样品体积、增加粒度信息以及制定合适的取样计划。文中展示了改进的光阻法在治疗性蛋白质产品上的成功应用，并讨论了在产品开发的不同阶段使用补充方法和技术的策略。
