Huang Chi-Ting, Sharma Deepak, Oma Peter, Krishnamurthy Rajesh
Acceleron Pharma, 149 Sidney Street, Cambridge, Massachusetts 02139, USA.
J Pharm Sci. 2009 Sep;98(9):3058-71. doi: 10.1002/jps.21575.
The U.S. and European Pharmacopeias require subvisible (> or =10 and > or =25 microm) and visible particulate testing of therapeutics to ensure their safety and suitability for clinical use. The objective of this article is to compare the sizing and counting accuracies of light obscuration, which is the standard technique used to measure subvisible particulate matter, and Micro-Flow Imaging (MFI), a new imaging-based technology. An immunoconjugate was selected as the model protein for this study since it could be induced to form particulate matter in PBS. Light obscuration was performed as described in USP chapter <788> while MFI measurements were conducted per the manufacturer's procedures. The two techniques yielded similar results when polystyrene standards were analyzed. However, the MFI measurements indicated the presence of significantly more particles in the protein-containing solution compared to the light obscuration measurements. The presence of nonspherical protein particles as well as particles that possess a refractive index similar to the solvent that they are in appear to be detected by MFI, but not by light obscuration, leading to the difference in the results. Imaging-based technologies could aid in developing formulations and processes that would minimize the formation of protein particulates.
美国和欧洲药典要求对治疗药物进行亚可见（≥10和≥25微米）和可见微粒检测，以确保其安全性和临床使用的适用性。本文的目的是比较用于测量亚可见微粒物质的标准技术光阻法与一种基于成像的新技术微流成像（MFI）的粒径测定和计数准确性。由于免疫缀合物在PBS中可诱导形成微粒，因此选择其作为本研究的模型蛋白。光阻法按照美国药典第<788>章所述进行，而MFI测量则按照制造商的程序进行。分析聚苯乙烯标准品时，这两种技术得出了相似的结果。然而，与光阻法测量相比，MFI测量表明含蛋白质溶液中的颗粒明显更多。MFI似乎能检测到非球形蛋白质颗粒以及折射率与其所在溶剂相似的颗粒的存在，但光阻法却检测不到，这导致了结果上的差异。基于成像的技术有助于开发能尽量减少蛋白质微粒形成的制剂和工艺。
