Akhunzada Zahir S, Hubert Mario, Sahin Erinc, Pratt James
BMS via PPD, DPST, Material Science & Engineering, New Brunswick, New Jersey 08903, United States.
One Squibb Drive, New Brunswick, New Jersey 08903, United States.
Curr Pharm Biotechnol. 2019;20(3):232-244. doi: 10.2174/1389201020666190214100840.
The presence of subvisible particles (SVPs) in parenteral formulations of biologics is a major challenge in the development of therapeutic protein formulations. Distinction between proteinaceous and non-proteinaceous SVPs is vital in monitoring formulation stability.
The current compendial method based on light obscuration (LO) has limitations in the analysis of translucent/low refractive index particles. A number of attempts have been made to develop an unambiguous method to characterize SVPs, albeit with limited success.
Herein, we describe a robust method that characterizes and distinguishes both potentially proteinaceous and non-proteinaceous SVPs in protein formulations using Microflow imaging (MFI) in conjunction with the MVAS software (MFI View Analysis Suite), developed by ProteinSimple. The method utilizes two Intensity parameters and a morphological filter that successfully distinguishes proteinaceous SVPs from non-proteinaceous SVPs and mixed aggregates.
The MFI generated raw data of a protein sample is processed through Lumetics LINK software that applies an in-house developed filter to separate proteinaceous from the rest of the particulates.
生物制品注射用制剂中存在亚可见颗粒（SVPs）是治疗性蛋白质制剂开发中的一项重大挑战。区分蛋白质类和非蛋白质类SVPs对于监测制剂稳定性至关重要。
当前基于光阻法（LO）的药典方法在分析半透明/低折射率颗粒方面存在局限性。人们已多次尝试开发一种明确的方法来表征SVPs，但成效有限。
在此，我们描述了一种稳健的方法，该方法使用微流成像（MFI）结合ProteinSimple公司开发的MVAS软件（MFI视图分析套件），对蛋白质制剂中潜在的蛋白质类和非蛋白质类SVPs进行表征和区分。该方法利用两个强度参数和一个形态学过滤器，成功地将蛋白质类SVPs与非蛋白质类SVPs及混合聚集体区分开来。
通过Lumetics LINK软件处理蛋白质样品的MFI生成的原始数据，该软件应用自行开发的过滤器将蛋白质类颗粒与其他颗粒分开。
