Jenke Dennis
Trial Scientific Solutions, LLC, 181 Peregrine Lane, Hawthorn Wood, IL 60047
PDA J Pharm Sci Technol. 2023 Jul-Aug;77(4):329-338. doi: 10.5731/pdajpst.2021.012671. Epub 2023 Mar 31.
Drug products and medical devices can contain leachable impurities that could adversely affect patient health during their clinical use. To establish patient exposure to leachables, drug products and packaging, manufacturing system, or medical device extracts are analytically screened for leachables or extractables. For organic extractables/leachables, the screening process typically involves a chromatographic separation coupled with an information-rich detection method. Information contained in the detector response (e.g., the chromatographic peak) is processed to establish quantities and to elucidate identities for the detected compounds. Organic extractables and leachables screening methods and procedures have proliferated with little, if any, attempt at standardization, creating the situation in which virtually every testing laboratory has their own analytical testing and data processing methodology. This raises the possibility that two different labs screening the same extract or drug product would report extractables or leachables profiles that differ in the number of compounds reported, the identities of the reported compounds, and the extracted (or leached) amounts of the identified compounds. Although standardization of the screening methods and procedures themselves would reduce lab-to-lab variation, such an approach would be difficult to implement. Thus, standardization of the screening outputs by setting quality standards for the outputs is considered. For example, the method's ability to detect a broad cross-section of potential extractables/leachables is established by testing a test mixture of representative compounds. Additionally, this author proposes that reported compound identities should be confident to be used in safety risk assessment; use of lower quality identities requires that the lower quality be accounted for in the assessment, perhaps by use of an uncertainty factor. Similarly, it is proposed that reported concentrations should be semi-quantitative to be used in safety risk assessment; use of lower quality concentrations requires that the lower quality be accounted for in the safety risk assessment, perhaps by use of an uncertainty factor.
药品和医疗器械可能含有可浸出杂质，这些杂质在临床使用过程中可能会对患者健康产生不利影响。为了确定患者对可浸出物的接触情况，需要对药品及其包装、生产系统或医疗器械提取物进行可浸出物或可提取物的分析筛选。对于有机可提取物/可浸出物，筛选过程通常包括色谱分离和信息丰富的检测方法。处理检测器响应（例如色谱峰）中包含的信息，以确定所检测化合物的数量并阐明其身份。有机可提取物和可浸出物的筛选方法和程序大量涌现，但几乎没有（如果有的话）标准化的尝试，导致几乎每个检测实验室都有自己的分析测试和数据处理方法。这就增加了一种可能性，即两个不同的实验室对同一提取物或药品进行筛选时，报告的可提取物或可浸出物谱在报告的化合物数量、报告化合物的身份以及已鉴定化合物的提取（或浸出）量方面会有所不同。尽管筛选方法和程序本身的标准化会减少实验室之间的差异，但这种方法难以实施。因此，考虑通过为输出设置质量标准来实现筛选输出的标准化。例如，通过测试代表性化合物的测试混合物来确定该方法检测潜在可提取物/可浸出物广泛范围的能力。此外，本文作者建议，报告的化合物身份应具有足够的可信度，以便用于安全风险评估；使用质量较低的身份时，需要在评估中考虑较低的质量，可能通过使用不确定因子来实现。同样，建议报告的浓度应为半定量，以便用于安全风险评估；使用质量较低的浓度时，需要在安全风险评估中考虑较低的质量，可能通过使用不确定因子来实现。
