21世纪的清洁验证原料药的清洁接受标准-InternationalSocietyfor.PDFVIP

21 世纪的清洁验证：原料药的清洁接受标准 本文讨论了如何从临床和毒理学研究建立真正的以科学为基础的限度，以风险分析为基础的方法来评估清 洁验证数据，从此数据为基础数据设置统计过程控制限额。 Introduction Part I of this article1 discussed the history of Cleaning Validation Acceptance Limits for Active Pharmaceutical Ingredients and where the currently used industry limits came from, analyzed the current approaches to setting acceptance limits, and discussed some of the problems and weaknesses of these approaches. Part II will discuss how to establish true science-based limits using data from clinical and toxicological studies, a risk-based approach to evaluating cleaning validation data, and guidance on setting statistical process control limits from that data. 介绍 本文的第一部分讨论了原料药的清洁验证验收标准的历史和现行的行业限度出处，分析了目前设置验收标 准的做法，并讨论了这些方法的问题和不足。第二部分将讨论如何从临床和毒理学研究建立真正的以科学 为基础的限度，以风险为基础的方法来评估清洁验证数据，从数据统计过程控制限度的指导数据。 Establishing Science-Based Limits As discussed at the end of Part I, setting cleaning validation limits based on all available safety data is much preferred over an approach that considers only one factor (therapeutic dose). ISPE’s recently published Risk-MaPP Baseline Guide2 goes into great detail in describing how to set health-based limits using all the toxicological and clinical data available. Although Risk-MaPP is new and is structured to align with the principles described in the recent ICH Q9 document, much of its contents are based on long-existing principles and long-used procedures in toxicology. The following discussion will summarize some of the guidance on determining health-based limits provided in the Risk-MaPP Guide. 建立以科学为基础的限度 在第一部分最后的讨论中，设置清洁限度时基于所有可用的安全数据比只应用一个因子（治疗剂量）要好 得多。ISPE 的最近公布的基线指南2 风险MaPP 到非常详细的描述如何使用所有可用的毒理和临床数据设置 基于健康基础的限制。虽然风险MAPP 是ICH Q9 在新的最近的文件中结构调整后所述的原则，但是其内容 多是在毒理学上基于长期存在的原则和长期使用的程序。下面的讨论中会总结一些指导，确定风险 MAPP 指南提供的基于健康的限度。 Before attempting to set limits of any kind, it is impo