ich-Q10（中英文对照） - 图文

These elements should be applied in a manner that is 适当并按比例地将这些要素应用于产品生命周appropriate and proportionate to each of the product 期的各个阶段，认识到各个阶段的差异和不同的lifecycle stages, recognising the differences among, and 目标。 the different goals of, each stage.

Throughout the product lifecycle, companies are 在产品的生命周期中，鼓励公司评价改进产品质encouraged to evaluate opportunities for innovative 量的创新方法的机会。 approaches to improve product quality.

Each element is followed by a table of example 每个要素按药物生命周期的各个阶段要素的应applications of the element to the stages of the 用实例的表格进行。 pharmaceutical lifecycle.

3.2.1 Process Performance and Product Quality Monitoring System

Pharmaceutical companies should plan and execute a system for the monitoring of process performance and product quality to ensure a state of control is maintained. An effective monitoring system provides assurance of the continued capability of processes and controls to produce a product of desired quality and to identify areas for continual improvement. The process performance and product quality monitoring system should:

(a) Use quality risk management to establish the

control strategy. This can include parameters and attributes related to drug substance and drug product materials and components, facility and equipment operating conditions, in-process controls, finished product specifications, and the associated method sand frequency of monitoring and control. The control strategy should facilitate timely feedback / feedforward and appropriate corrective action and preventive action;

(b) Provide the tools for measurement and analysis

of parameters and attributes identified in the control strategy (e.g., data management and statistical tools);

(c) Analyse parameters and attributes identified in

the control strategy to verify continued operation within a state of control;

(d) Identify sources of variation affecting process

performance and product quality for potential continual improvement activities to reduce or control variation;

(e) Include feedback on product quality from both

internal and external sources, e.g., complaints, product rejections, non-conformances, recalls, deviations, audits and regulatory inspections and findings;

3．2．1工艺性能和产品质量监控系统 制药企业应规划和执行工艺性能和产品质量监控体系以确保控制状态得到了维持。有效的监控体系保证了持续性工艺性能和控制，以生产出需要的质量的产品和确定持续改进的范畴。工艺性能和产品质量监控体系应： (a)应用质量风险管理以建立控制策略，可以包

括原料药及药用物质和组份相关参数与属性，设施和设备运行条件，过程控制，成品质量标准，及监控和控制的相关方法与频率。控制策略应促进及时反馈/前馈及适宜的纠正措施和预防措施。

(b)提供控制策略中所确定参数与属性的衡量与分析工具，比如数据管理和统计工具 (c)分析控制策略中所确定参数与属性以证实后续操作受控

(d)确定影响工艺性能和产品质量的变量，持续改进活动会减少或控制这些变量

(e)包括产品质量的内外部反馈，如投诉，产品否决，不合格，召回，偏差，审计和官方检查与发现

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(f) Provide knowledge to enhance process

understanding, enrich the design space (where established), and enable innovative approaches to process validation.

(f)提供知识以增强工艺理解，丰富设计空间（如建立的话），并实现工艺验证的创新方法

Table I: Application of Process Performance and Product Quality Monitoring System throughout the Product Lifecycle 表1：工艺性能和产品质量监控在整个生命周期内的应用 Pharmaceutical Development 药物开发 Process and product knowledge generated and process and product monitoring conducted throughout development can be used to establish a control strategy for manufacturing. 开发过程中所做的产品监控和产生的工艺和产品知识可以用于建立生产的策略控制。 Technology Transfer 技术转移 Monitoring during Commercial Manufacturing 商业化生产 Product Discontinuation 产品终止 ceases, monitoring such as stability testing should continue to completion of the studies. Appropriate action on marketed product should continue to be executed according to regional regulations. 一旦生产终止，如稳定性研究等监控应继续以Page 14 of 28

A well-defined system Once manufacturing scale-up activities can for process provide a preliminary performance and indication of process performance and the into manufacturing. Knowledge obtained during transfer and be useful in further strategy. 工艺放大活动中的监控product quality monitoring should be performance within a state of control and to identify improvement 应运用良好的工艺性能确保性能受控并确定改进领域。 successful integration applied to assure scale up activities can areas. developing the control 和产品质量监控体系来能为工艺性能和为成功整合到生产中去提供初步的指示。转移和工艺放大活动中获得的知识能被用于进一步开发控制策略。 完成该研究。应根据区域法规要求继续执行已销售产品的相关措施。 3.2.2 Corrective Action and Preventive 3．2．2纠正预防措施体系 Action (CAPA) System

The pharmaceutical company should have a 对于由调查研究投诉，产品否决，不合格，召system for implementing corrective actions 回，偏差，审计，官方检查和发现，及工艺性and preventive actions resulting from the 能趋势和产品质量监控等而产生的纠正措施和investigation rejections, findings,

of

complaints,

product 预防措施，制药企业应有体系来执行这些措施。recalls, 应运用结构化的调查研究方法来确定根本原process 与风险水平ICH Q9相当。CAPA系列方法应使

non-conformances, and

trends

from

deviations, audits, regulatory inspections and 因。调查研究的努力水平，正式程序和文件应performance and product quality monitoring. 产品和工艺得到提高，产品和工艺的理解得到A structured approach to the investigation 加强。 process should be used with the objective of determining the root cause. The level of effort, formality, and documentation of the investigation should be commensurate with the level of risk, in line with ICH Q9. CAPA methodology should result in product and process improvements and enhanced product and process understanding.

Table II: Application of Corrective Action and Preventive Action System

throughout the Product Lifecycle

表2：纠正措施/预防措施在整个产品生命周期内的应用 Pharmaceutical Development 药物开发 Product or process variability is explored. CAPA methodology is useful where corrective actions and preventive actions are incorporated into the iterative design and

Technology Transfer 技术转移 CAPA can be used as an effective system for feedback, feed improvement. CAPA可被用于反馈，前馈和持续改进的有效体系。 Commercial Manufacturing 商业化生产 CAPA should be used and the effectiveness of the actions should 应运用CAPA，并应评估其效果。 Product Discontinuation 产品终止 CAPA should continue after the product is discontinued. The impact on product remaining on the market should be considered as well as Page 15 of 28

forward and continual be evaluated. development process. 开发产品或工艺变量。当纠正措施和预防措施被整合进入了反复设计和开发流程，CAPA系列方法是有用的。 other products which might be impacted. 在产品终止后，应继续CAPA。应考虑还在市场上的产品的影响及可能会受到影响的产品。 3.2.3 Change Management System

3．2．3变更管理体系

Innovation, continual improvement, the 革新，持续改进，工艺性能和产品质量监控及outputs of process performance and product quality monitoring and CAPA drive change. In order to evaluate, approve and implement these changes properly, a company should have an effective change management system. There is generally a difference in formality of change management processes prior to the initial regulatory submission and after submission, where changes to the regulatory filing might be required under regional requirements.

The change management system ensures continual improvement is undertaken in a timely and effective manner. It should provide a high degree of assurance there are no unintended consequences of the change.

The change management system should include the following, as appropriate for the stage of the lifecycle:

(a) Quality risk management should be

utilised to evaluate proposed changes. The level of effort and formality of the evaluation should be commensurate with the level of risk;

(b) Proposed changes should be

evaluated relative to the marketing authorisation, including design space, where established, and/or current product and process understanding. There should be an assessment to determine whether a change to the regulatory filing is required under regional requirements. As stated in ICH Q8, working within the design space is not

CAPA都会趋势变更。为了适宜地评估，批准和执行这些变更，公司应具有有效的变更管理体系。一般来说，注册文件递交前后的变更管理流程是有些区别的，需遵从区域法规的要求进行注册文件的变更。 变更管理体系确保持续改进得到了及时有效的执行，并高度保证变更不会引发不期望的后果。 变更管理体系应在生命周期的各个阶段包括如下： (a)运用质量风险管理评估计划的变更。评

估的努力程序与正式程序应与风险水平相当。

(b)应根据相关的上市许可，设计空间（如

建立的话），和/或现行产品和工艺理解对计划的变更进行评估。需通过评估确定是否需要根据区域要求进行注册文件的变更。如ICH Q8所述，设计空间内的变动不被认为是变更（从注册文件的角度来看）。但是从制药质量体系的立场来看，所有的变更均需根据公司的变更管理体系进行评估。

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