a Research Center Pharmaceutical Engineering GmbH , Graz , Austria.
b Baxter AG , Vienna , Austria.
Pharm Dev Technol. 2019 Jul;24(6):739-750. doi: 10.1080/10837450.2019.1585449. Epub 2019 Apr 3.
An undesirable characteristic in lyophilized parenteral products is the potential presence of particulate matter in the final product, which may affect patient safety. In this study, quality risk management tools described in the International Conference on Harmonization Guideline Q9 were used to estimate the risks for a pharmaceutical manufacturing line, based on three critical quality attributes: (1) visible particulate matter; (2) lyo-cake collapse traces; and (3) lyo-cake melt-back traces. Together with a Process Failure Mode Effect Analysis (PFMEA), an input-output analysis of the individual unit operations identified seven major material classes of extrinsic particulate matter. In addition to the process assessment, an experimental investigation of the location of impurities in lyophilized products was performed. To that end, intentionally contaminated vials were examined to locate the particulate matter and its possible migration. The results emphasize the importance of a full transmission mode release testing since the particles may enter the interior of the lyo-cake. A theoretical explanation of the observed impurity locations is provided.
在冻干的注射产品中，一个不理想的特性是最终产品中可能存在微粒物质，这可能会影响患者的安全。在这项研究中，使用了国际协调会议指南 Q9 中描述的质量风险管理工具，根据三个关键质量属性（1）可见微粒物质；（2）冻干蛋糕塌陷痕迹；和（3）冻干蛋糕回熔痕迹，来评估制药生产线的风险。结合过程失效模式影响分析（PFMEA），对各个单元操作的输入-输出分析确定了七种主要的外来微粒物质的材料类别。除了工艺评估之外，还对冻干产品中杂质的位置进行了实验研究。为此，对故意污染的小瓶进行了检查，以确定微粒物质及其可能的迁移位置。结果强调了进行全传输模式放行测试的重要性，因为这些颗粒可能会进入冻干蛋糕的内部。对观察到的杂质位置提供了理论解释。
