质量风险管理：检查员在找什么

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ECA新闻--Julia法规翻译

Quality Risk Management:What Inspectors are looking for

质量风险管理：检查员在找什么

ICH Q9 is the major guidelineproviding principles and examples of tools for Quality Risk Management (QRM)that can be applied to different aspects of pharmaceutical quality.

ICH Q9是提供质量风险管理(QRM)原则和工具示例的主要指南，它适用于药物质量的不同方面。

Quality Risk Management itself plays an importantrole in the EU-GMP Guidelines. For example, in Annex 16 to the EU-GMPGuidelines (Certification by a Qualified Person and Batch Release) the term"risk management" is referenced six times. In the current draft ofthe revised Annex 1 (Manufacture of Sterile Medicinal Products) the term"risk management" can be found 4 times and "riskassessment" 25 times! But the main reference lies in the EU-GMPGuidelines, Part 1, chapter 1: "To achieve the quality objectivereliably there must be a comprehensively designed and correctly implementedsystem of Quality Assurance incorporating Good Manufacturing Practice, QualityControl and Quality Risk Management. It should be fully documented and itseffectiveness monitored".  Now, with ICH Q12, a marketingauthorisation holder (MAH) may propose reporting categories for post-approvalchanges based on risk and knowledge gained in pharmaceutical development.

质量风险管理本身在EU GMP指南中有着重要作用。例如，在EU GMP指南附录16中（QP认证和批放行），术语“风险管理”出现了6次。在修订后的附录1（无菌药品生产）草案中，术语“风险管理”出现了4次，“风险评估”出现了25次之多！但主要的引用是在EU GMP指南第1部分第1章里“为可靠达成质量目标，必须全面设计并正确实施质量保证体系，结合CGMP、质量控制和质量风险管理。上述内容应全部记录并有效监控”。现在，有了ICH Q12，上市许可持有人（MAH）可以基于风险和药物开发中所获得的知识来提议报告批准后变更分类。

Other GMP areas where risk management principlesare used are for example:

风险管理原则应用的其它GMP领域有例如：

• Deviation Management and CAPA 偏差管理和CAPA
• Evaluating quality product defects 质量产品缺陷评估
• Change Control 变更控制
• Determination of the scope and extent of qualification and validation activities 确认和验证活动范围和程度确定
• Monitoring and sampling processes 监测和取样程序
• Document reviews 文件审核
• Supplier Qualification 供应商确认
• Material Management 物料管理
• Making justification within "unless otherwise justified" concepts “另有论证者除外”概念内做出论证
• etc.     等等
  
  

And ICH Q9 describes some of the most importanttools to implement respective risk management and assessment principles.Quality risk management activities are usually, but not always, undertaken byinterdisciplinary teams. When teams are formed, they should include expertsfrom the appropriate areas.

ICH Q9阐述了实施相关风险管理和评估原则的最重要工具。质量风险管理活动通常，但并不总是，由多学科团队来执行。团队组成应包括来自适当领域的专家。

But how do competent authorities look at thesesystems in their GMP inspections?

但药监当局在其GMP检查过程中是如何查看这些体系的呢？

If the company explains that ICH Q9 has been usedas basis for establishing the QRM system, it will likely be used by inspectorsas a reference. Independent from that, inspectors might review

如果公司解释说已采用ICH Q9作为基础建立QRM体系，则检查员很可能将其用作参考信息。在此以外，检查人员可能会查看：

• Integration of QRM systems in the Quality System 质量体系中QRM体系整合
• Definition of risk 风险定义
• Appropriate set-up of QRM teams QRM团队组成是否恰当
• Decision making processes and their traceability and transparency 决策流程及其可追溯性和透明度
• Implementation of defined actions  所确定措施的实施
• The link to continual improvement processes 与持续改进程序的关联
  
  

Examples can be seen in the following excerptsfrom FDA Warning Letters:

在以下FDA警告信摘录中可以看到一些例子：

• "You did not provide a risk assessment evaluating the potential effect of your deviations on the quality of API you previously repackaged and released." 你们未提交风险评估，评估你们偏差对你们之前重新包装和放行的API质量的潜在影响
• "Your response is inadequate because you did not provide a risk assessment of the lots tested with the unqualified secondary reference standards." 你们的回复是不充分的，因为你们未提交采用未经确认的二级对照品进行检测的批次的风险评估
• "Your     strategy should include … a comprehensive description of the root causes of your data integrity lapses, including evidence that the scope and depth of the current action plan is commensurate with the findings of the investigation and risk assessment." 你们的策略应包括……一份你们数据完整性受损根本原因的全面描述，包括当前措施计划的范围和程度与检查缺陷相称的程序和风险评估
• "FDA strongly recommends that your management immediately undertake a comprehensive assessment of your operations, including facility design, procedures, personnel, processes, materials, and systems." FDA强烈建议你们管理层立即对你们的操作，包括工厂设计、程序、人员、工艺、物料和体系进行全面评估
• "Provide an assessment of the cross-contamination risks due to your current practices for the material flow of solvents, and any corrective actions resulting from this assessment. Also, provide an assessment of the contamination risk for batches within expiry." 请提交一份由于你们当前溶剂物料流做法引起的交叉污染风险的评估，以及此评估所引出的任何纠正措施。还请提交一份仍在有效期内的批次污染风险的评估
• "In response to this letter, provide the following: (…) a risk assessment regarding the effects of your supplier changes on the distributed API." 在回复此函时，请提交以下：（……）一份关于你们供应商变更对已销售API的影响风险评估
• "In response to this letter, provide a comprehensive assessment of all in-process OOS results for (…), including root causes. Extend this assessment to other batches that might have been affected." 在回复此函时，请提交一份（……）所有中控OOS结果包括根本原因的全面评估。请延伸此评估至其它可能受影响的批次。
• [In your response provide] "A current risk assessment of the potential effects of the observed failures on the quality of your drugs. Your assessment should include analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity, and risks posed by ongoing operations." 【在你们提交的回复中】当前对已发现失败对你们药品质量的潜在影响风险评估。你们的评估应包括受到数据完整性影响的药品放行所导致的患者风险，以及持续运营所具有的风险的分析
  
  

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