Sartorius Stedim Biotech GmbH, August Spindler-Str. 11, 37079 Goettingen, Germany.
Sartorius Stedim Biotech GmbH, August Spindler-Str. 11, 37079 Goettingen, Germany.
Eur J Pharm Sci. 2021 Aug 1;163:105841. doi: 10.1016/j.ejps.2021.105841. Epub 2021 Apr 20.
Quantitative information on process equipment-related leachables (PERLs) is required for process qualification and within a safety assessment. Extractables data for single-use equipment are suitable and applicable if the extractables study conditions fit or are bracketing the expected conditions of use. It is necessary to extrapolate extractables data when the expected in-use conditions are not covered by the test conditions. Methods for such quantitative extrapolation of extractables data toward potential PERLs are therefore needed. They are comprehensively described in this publication and include: scaling of extractables data for devices of different sizes adjusted to process-volumes, extrapolation to temperatures different from the extraction temperature, extrapolations to different solvent compositions, extrapolation to various contact times, and the combination of extractables data from individual components to assess assemblies. These extrapolation methods yield extractables data as if an extractables study had been performed. The methods presented are consistently derived from basic physicochemical principles. The relevant, underlying physical parameters are obtained from extractables experiments and are compared with published data. The applicability and justification of the proposed calculation methods are discussed and benchmarked against experimental findings.
需要定量的工艺设备相关浸出物（PERLs）信息来进行工艺验证和安全性评估。如果单次使用设备的提取研究条件适合或涵盖了预期的使用条件，则提取数据是适用的。当预期的使用条件不在测试条件范围内时，需要对提取数据进行外推。因此，需要针对潜在的 PERLs 进行这种提取数据的定量外推的方法。本出版物全面描述了这些方法，包括：根据处理体积调整不同尺寸设备的提取数据的缩放、从提取温度外推至不同温度、从不同溶剂组成外推、从不同接触时间外推以及从各个组件的提取数据组合来评估组件。这些外推方法生成了提取数据，就好像已经进行了提取研究一样。所提出的方法均源自基本的物理化学原理。从提取实验中获得相关的基本物理参数，并与已发表的数据进行比较。讨论了所提出的计算方法的适用性和合理性，并与实验结果进行了基准测试。
