PDA TR60中关于工艺性能确认（PPQ）的描述

在PPQ研究中，已执行的成功批次数不应该作为PPQ的主要目的。虽然商业放大批成功运行批次数量可以说明操作的熟练以及充分的系统设计。通过这些批次，可以收集信息和数据，用来证明工艺控制策略是有效的。信息的类型和数量应建立在对工艺的理解上，建立在工艺变量对产品质量的影响上，建立在第一阶段工艺设计中开发的工艺控制策略上。如果适用的话，已有的知识也应该被利用。批次的数量被用来获取信息和数据，通过一定的方法证明批与批之间变化，CQA依然是可以接受的，这个方法的选择也会影响批次的数量。

This section will discuss design strategy for the PPQ, recommended content for the protocol and report, and the transition to Stage 3 of the process validation lifecycle.

本章节将讨论PPQ的控制策略，建议方案和报告的内容，以及如何过度到验证生命周期中的第三阶段。

4.2.1 PPQ Readiness

PPQ准备

The transition from Stage 1 to Stage 2 of the process validation lifecycle is not strictly sequential. Completion of some Stage 1 activities may overlap with those from Stage 2. Likewise, some preparative Stage 2 activities will be initiated in parallel with those from later Stage 1 activities. Components of Stage 1 PPQ activities (as discussed in Section 3.1) include, among others: drafting of the Process Validation Master Plan; initiation of the qualification of facilities, utilities, and equipment; drafting of protocols for the PPQ studies; training of personnel; or drafting an initial CPV plan. Although initiation of PPQ activities does not is not depend on completion of all Stage 1 activities, a readiness assessment should be conducted to determine the timing of sufficient information and completion of activities to support moving forward

with PPQ batch manufacture. The readiness assessment should include deliverables from Stage 1 (as outlined previously in Section 3.1) and other elements:

验证生命周期中，第一阶段过渡到第二阶段，不是严格按照顺序的。部分第一阶段工作可能与第二阶段工作同步完成。同样，部分第二阶段工作也会与第一阶段的后期工作同时启动。PPQ的第一阶段的内容（见章节3.1）包括：起草工艺验证主计划，设施；公用工程，设备的启动，起草PPQ方案，人员培训以及起草最初的CPV计划等。尽管PPQ不需要第一阶段全部完成后才可以启动，但是应该有充分的风险评估为了决定PPQ活动完成和获取充分信息的时间，这些可以保证PPQ批量生产的推进。充分的风险评估应包括第一阶段的结论（见3.1中的概述）和以下要素：

Quality Target Product Profile —Initiated in at the start of Stage 1, but updated to reflect knowledge obtained from Stage 1 prior to initiating PPQ.

目标产品质量概况-第一阶段的开始已经启动，但是在启动PPQ之前需根据第一阶段获得的知识进行更新。

Critical Quality Attributes with Criticality Assessment —CQAs are identified early in Stage 1. They are confirmed to account for additional analytical characterization, clinical and/or non-clinical data and information gathered during Stage 1. CPPs that impact CQAs are reviewed and updated based on

detectability and occurrence (11,36).

关键质量属性与关键评估-在第一阶段的早期阶段，CQA已经被明确定义。被证实的CQA来解释额外的分析特性，临床或者非临床的数据和第一阶段收集的信息。基于可检测率和发生的概率，影响CQA的CPPs应定期被审核和更新。

Commercial Manufacturing Process Deion —This is started in Stage 1 and updated to reflect the finalized commercial process supported by Stage 1 studies/data. These include elements outlined in Section 3.4, and any changes resulting from the qualification of the facilities, utilities, and equipment as outlined in Section 4.1.

商业生产工艺描述-商业生产工艺描述第一阶段已经开始并更新，来表现由第一阶段研究/数据支持的最终商业工艺。这些也包括3.4章节所概述的内容和4.1章节设施，设备和公用工程确认导致的变更。

Analytical Methods —Appropriately validated or suitably qualified methods should be identified and their status documented. Methods for product release and stability should be fully validated according to ICH requirements prior to initiating PPQ batch testing. Additional tests beyond normal release testing used to support PPQ should be identified and suitably qualified/validated prior to being used to test PPQ batches. The justification of the status for use in the PPQ studies (qualified and/or validated) should be fully documented for each analytical method.

分析方法-应确认分析方法已经验证或确认，他们验证状态应该被记录。根据ICH的要求，在PPQ批测试开始之前，产品放行和稳定性试验的方法应充分被验证。除了正常的批放行测试，新增的测试方法用于支持PPQ的，新的测试方法啊也需在PPQ批测试之前被验证。在PPQ的研究中，每一种分析方法验证状态评估（已确认或已验证）均需被记录。

Approved commercial batch records —Changes may be made to batch records during Stage 1 should enhance, clarify, or optimize manufacturing instructions and/or to reflect knowledge gained during process characterization. Batch records reflecting the final commercial process to be studied in PPQ should be approved prior to PPQ batch execution.

批准的商业批批记录-第一阶段，批记录有变更，在工艺特性确定期间，这些变更应该提高，清晰或者优化生产指令，并反映出该期间获得的知识。批记录反映了最终的商业批工艺，应在PPQ执行之前批准批记录。

Process Design Report —This report (as described in Section 3.11) is the repository for the process design justification, and includes parameter risk ranking, and ranges for the process that will undergo PPQ study. The data summarized in this report will support the selection of the elements of the PPQ studies and proposed PPQ acceptance criteria. The process development summary should provide the link between the detailed process deion, risk assessments, control strategy deion, characterization reports, rationale for parameter designations, and clinical manufacturing history. It is a best practice for this information to be finalized prior to PPQ study design since it provides the scientific support to justify the PPQ acceptance criteria.

工艺设计报告-工艺设计报告（3.11章节由描述）是工艺设计理由的依据，包括工艺参数风险排序，工艺范围，这些PPQ研究中都需描述。工艺设计报告中总结的数据用来支持PPQ中要素的选择和支持提出的PPQ接收标准。具体的工艺描述，风险评估，控制策略描述，工艺特性确认报告，参数类型的基本原理很临床生产历史这几者的关系在工艺开发报告中有概述。在PPQ研究之前，这些信息的完成是一个很好的实践，因为这些信息给PPQ的接收标准提供了可以的依据。

Process Validation Master Plan (PVMP) —Drafting of the process validation master should begin in Stage 1 and be finalized prior to PPQ study initiation. Elements of the Process Validation Master Plan are outlined in Section 3.12.

工艺验证主计划(PVMP)-工艺验证主计划应在第一阶段进行草早，在PPQ启动之前完成。工艺验证主计划要素的概述见章节3.12.

Quality System and Training —Qualified and trained personnel will be integral to the PPQ studies. Detailed, documented training specific to the PPQ is recommended for functional groups directly involved in the execution of the study. To minimize the risk of human error, personnel should understand their role in protocol execution to minimize the risk of human error. Quality Unit approval of PPQ activities should be completed prior to PPQ study initiation, and all PPQ studies should be conducted within the quality system.

质量系统和培训-有资质的和经过培训的人员是PPQ研究中必须要求的。相关的职能人员需进行关于PPQ的详细的，有记录的培训。同时，这些职能人员应直接参与到PPQ研究的执行中。为了尽量减少人员操作失误的风险，人员应理解他们在方案执行中的角色。在PPQ执行之前，质量部门应批准PPQ活动，同时，所以的PPQ研究应在质量系统的指导下进行。

Approved protocols for PPQ Studies —Protocols for each study should be approved and qualification protocols is discussed in Section 4.4.

PPQ研究方案的批准-每一个研究的方案均需被批准，确认方案在章节4.4中进行讨论。返回搜狐，查看更多