APIC 2^01405原料药厂清洁验证指南：4.0可接受标准.docVIP

APIC 201405原料药厂清洁验证指南：4.0可接受标准（上）（中英文） 注：本文件是由 CEFIC 的 APIC 内的清洗验证工作组制定。欧洲化学工业委员会(cefic,europeanchemicalindustrycouncil)4.0 Acceptance Criteria 可接受标准 4.1. Introduction 概述 Companies must demonstrate during validation that the cleaning procedure routinely employed for a piece of equipment limits potential carryover to an acceptable level. That limit established must be calculated based on sound scientific rational. 公司在验证时要证明各设备日常所用的清洁程序能将带入下一产品的潜在残留限制在一个可以接受的水平。所建立的限度必须进行科学合理的计算。 This section provides practical guidance as to how those acceptance criteria can be calculated. It is important that companies evaluate all cases individually. There may be specific instances where the product mix in the equipment requires further consideration. 本部分提供实用的指南，指导如何计算这些可接受标准。公司对各案进行各案评估是非常重要的。有时还需要考虑产品从哪步开始混入设备中。 The acceptance criteria preferably should be based on the Acceptable Daily Exposure (ADE) calculations whenever this data is available. The Acceptable Daily Exposure defines a limit at which a patient may be exposed every day for a lifetime with acceptable risks related to adverse health effects. Calculations of Acceptable Daily Exposures of API’s and intermediates are usually done with involvement of industrial hygienists and toxicologists, who review all available toxicology and clinical data to set the limits. The justification of the calculation should be documented. 如果可以获得可接受日暴露（ADE）值，最好依据其计算可接受标准。可接受日暴露限度定义的是患者终身每天暴露于该浓度，但对健康的不良影响仍处于可接受风险水平。原料药和中间体的ADE一般由企业的卫生学家和毒理学家来制订，他们会审核各种可以获得的毒性和临床数据来设定限度。计算的合理性要进行记录。 In many cases Occupational Exposure Limits (OEL) will be defined for API’s, Intermediates and Industrial Chemicals by Industrial Hygienists and toxicologists and the OEL data is then used to define containment measures such that operators are adequately protected while working with the chemicals. 在很多情况下，会由行业卫生学家和毒理学家对原料药、中间体和工业级化学品的职业暴露限度（OEL）值进行界定，这时应使用OEL数据来制订限制措施，例如，操作人员在操作化学物质时需要受到充分保护。 The OEL data can also be used to calculate the ADE for cleaning of eq