1.1 本规程提供了用于确定残留物目视检测限值的统计有效程序，以及检验人员对药品制造设备表面和医疗器械进行残留物目视检查的资格。 1.2 本规程适用于药品（包括活性药物成分（API）；剂型；以及非处方、兽医、生物制剂和临床用品）和医疗器械。本规程也适用于其他健康、化妆品和消费品。 1.3 本规程适用于许多类型的化学残留物（包括原料药、中间体、清洁剂、加工助剂、加工油等），这些残留物可能残留在经过所有制造步骤（包括清洁）的制造设备表面或医疗器械上。 1.4 本规程仅适用于通过质量风险管理计划证明具有可接受危害分析、具有可重复和验证的清洁过程以及可依靠目视检查确定设备清洁度达到HBEL证明的残留限值的设备或装置。 1.5 国际单位制（SI）单位中规定的数值应视为标准值。本标准不包括其他测量单位。 1.6 本标准并不旨在解决与其使用相关的所有安全问题（如有）。本标准的使用者有责任在使用前建立适当的安全、健康和环境实践，并确定监管限制的适用性。 1.7 本国际标准是根据世界贸易组织技术性贸易壁垒（TBT）委员会发布的《国际标准、指南和建议制定原则决定》中确立的国际公认标准化原则制定的。 =====意义和用途====== 4.1 本实践中描述的方法应用指南中介绍的基于科学、基于风险和基于统计的概念和原则 第3106页 和 第219页 . 4.2 本规程中所述方法的应用提供了一种基于科学、风险和统计的方法，用于根据21 CFR 211.67（b）（6）对设备进行清洁度检查，并符合FDA过程验证指南生命周期方法。 4.3 本规程中所述方法的应用提供了一种基于科学、风险和统计的方法，用于根据欧洲药品管理局（EMA）附件15对设备的清洁度进行目视检查。 4.4 本规程中所述方法的应用提供了一种基于科学、风险和统计的方法，用于根据EMA的问答指南（问答#7和#8）对设备的清洁度进行目视检查 ( 2. ) . 4.5 目视检查，如中所述 4.4 应仅在VRL和MSSR之间有适当的安全裕度以及VRL处的鲁棒可检测性的情况下使用。 4.6 本实践中所述方法的应用适用ICH Q9中介绍的基于风险的概念和原则。 如ICH Q9中所述，验证（包括清洁验证）的工作水平、形式和文件编制也应与风险水平相称。 4.7 本实践中所述方法的应用提供了一种基于科学、风险和统计的方法，用于释放制造设备和制造的医疗器械或清洁度，该方法符合美国FDA工业指南，PAT–创新药物开发、制造和质量保证框架。 4.8 关键概念- 本实践应用了以下关键概念:( 1. )目视检查( 2. )质量风险管理( 3. )基于科学的方法( 4. )基于统计的方法，以及( 5. )过程知识和理解。

1.1 This practice provides statistically valid procedures for determining the visual detection limit of residues and the qualification of inspectors to perform the visual inspection of pharmaceutical manufacturing equipment surfaces and medical devices for residues. 1.2 This practice applies to pharmaceuticals (including active pharmaceutical ingredients (APIs); dosage forms; and over-the-counter, veterinary, biologics, and clinical supplies) and medical devices following all manufacturing and cleaning. This practice is also applicable to other health, cosmetics, and consumer products. 1.3 This practice applies to many types of chemical residues (including APIs, intermediates, cleaning agents, processing aids, machining oils, and so forth) that could remain on manufacturing equipment surfaces or medical devices that have undergone all manufacturing steps including cleaning. 1.4 This practice applies only to equipment or devices that have been justified through a Quality Risk Management program to have an acceptable hazard analysis, have cleaning processes that are repeatable and validated and where Visual Inspection can be relied upon to determine the cleanliness of the equipment at the residue limit justified by the HBEL. 1.5 The values stated in International System of Units (SI) units are to be regarded as standard. No other units of measurement are included in this standard. 1.6 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use. 1.7 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee. ====== Significance And Use ====== 4.1 Application of the approach described within this practice applies the science-based, risk-based, and statistics-based concepts and principles introduced in Guides E3106 and E3219 . 4.2 Application of the approach described within this practice provides a science-, risk-, and statistical-based approach for qualifying the inspection of equipment for cleanliness in accordance with 21 CFR 211.67(b)(6) and is in accordance with FDA Process Validation Guidance Life Cycle approach. 4.3 Application of the approach described within this practice provides a science-, risk-, and statistical-based approach for qualifying the visual inspection of equipment for cleanliness in accordance with European Medicines Agency (EMA) Annex 15. 4.4 Application of the approach described within this practice provides a science-, risk-, and statistical-based approach for qualifying the visual inspection of equipment for cleanliness in accordance with the EMA’s Q&A Guidance (Q&A’s #7 and #8) ( 2 ) . 4.5 Visual Inspection used as described in 4.4 should only be used in situations where there is a suitable safety margin between the VRL and MSSR and robust detectability at the VRL. 4.6 Application of the approach described within this practice applies the risk-based concepts and principles introduced in ICH Q9. As stated in ICH Q9, the level of effort, formality, and documentation for validation (including cleaning validation) should also be commensurate with the level of risk. 4.7 Application of the approach described within this practice provides a science-, risk-, and statistical-based approach for releasing manufacturing equipment and manufactured medical devices or cleanliness that is compatible with the U.S. FDA Guidance for Industry, PAT – A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance. 4.8 Key Concepts— This practice applies the following key concepts: ( 1 ) visual inspection, ( 2 ) quality risk management, ( 3 ) science-based approach, ( 4 ) statistics-based approach, and ( 5 ) process knowledge and understanding.