Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
Regul Toxicol Pharmacol. 2013 Feb;65(1):157-61. doi: 10.1016/j.yrtph.2012.08.002. Epub 2012 Aug 17.
Cleaning validation programs are developed to demonstrate acceptable carryover of drug substances/products when multiple drug substances are manufactured in shared process equipment. The International Society of Pharmaceutical Engineers (ISPE) developed a guidance document in 2010 describing the Risk-Based Manufacture of Pharmaceutical Products (referred to as RiskMAPP) (ISPE, 2010). This guidance document developed the concept of an acceptable daily exposure (ADE), which is the toxicologically acceptable daily dose for the first drug substance used in processing drug equipment (DS(A)) without prior knowledge of the subsequent drug substance (DS(B)). This paper discusses an extension of the ADE methodology called the product-specific ADE (PSADE) which is derived when DS(B) is known. Four case studies demonstrate examples in which the PSADE can be scientifically supported in lieu of the ADE and highlight some limitations in its application. The PSADE approach can be used to justify higher acceptance limits for cleaning validation when the ADE based acceptance limits are below the process capability limit of the cleaning process or limit of quantitation of the analytical method.
清洁验证方案旨在证明当多种药物在共用的生产设备中制造时，药物物质/产品的可接受的残留。国际制药工程师协会（ISPE）于 2010 年制定了一份指导文件，描述了基于风险的药物产品制造（简称 RiskMAPP）（ISPE，2010）。本指导文件提出了可接受的每日暴露量（ADE）的概念，即对于在处理药物设备中使用的第一种药物物质（DS(A）），在没有随后的药物物质（DS(B））的事先知识的情况下，其毒理学可接受的日剂量。本文讨论了一种 ADE 方法的扩展，称为特定于产品的 ADE（PSADE），当 DS(B）已知时，就可以得出该方法。四个案例研究展示了当 ADE 基于的接受标准低于清洁过程的过程能力极限或分析方法的定量极限时，PSADE 如何在科学上支持清洁验证的更高接受标准，并强调了其应用的一些局限性。PSADE 方法可用于证明清洁验证的接受标准更高，而 ADE 基于的接受标准低于清洁过程的过程能力极限或分析方法的定量极限。
