Design space verification should not beconfused with process validation. Both take into consideration prior knowledgeand development conclusions and are conducted at commercial scale, however the scopeof the studies are not the same. Whereasprocess validation demonstrates consistency of the process at normal operatingranges, design space verification demonstrates that scale effect and or modelassumptions are under control in the new area of design space and do not affectproduct quality. Unlike validation which covers all the steps of themanufacturing process, verification studies refer only to those operations wherea design space has been proposed.

设计空间验证不应与工艺验证相混淆。两者都考虑了先验知识和开发结论，并以商业规模进行，但研究范围并不相同。工艺验证表明工艺在正常操作范围内的一致性，而设计空间验证表明规模效应和/或模型假设在设计空间的新区域受到控制，不会影响产品质量。与涵盖生产过程所有步骤的验证不同，验证研究仅涉及已提出设计空间的那些操作。

In order to address the risks identifiedduring the risk assessment of operating in the unverified area of the designspace the verification studies may also include testing/monitoring ofadditional parameters or at an increased frequency as compared to the routinecontrol strategy.

为了解决在设计空间的未验证区域进行的风险评估过程中识别的风险，验证研究还可能包括测试/监控其他参数或与常规控制策略相比增加频率。

When verification data proves that theextent of movement within the design space is of high risk (e.g. critical qualityattributes are met but close to edge of failure identified at laboratory/pilotscale), process validation (consistency of the process) in the new area of designspace (new NOR) should also be considered.

当验证数据证明设计空间内的移动程度具有高风险（例如，满足关键质量属性但接近实验室/中试规模确定的失败边缘）时，还应考虑设计空间新区域（新 NOR）的工艺验证（工艺的一致性）。

A protocol for design space verification shouldbe submitted in section 3.2.R. irrespective of the

validation approach. When a strategy forcontinuous verification is envisaged, where relevant, the elements of design spaceverification should be included as part of the continuous verification protocol.

不考虑验证方法，应在第3.2.R节中提交设计空间验证方案。当设想连续验证策略时，在相关的情况下，设计空间验证的元素应作为连续验证方案的一部分包含在内。

It is understood that when an applicant candemonstrate that the design space is scale independent then a verificationprotocol is not requested in the dossier.

可以理解的是，当申请人可以证明设计空间不依赖于规模时，则不需要在申请文件中提供验证方案。

NB: Continuous Process Verification is analternative approach to traditional process validation in which manufacturingprocess performance is continuously monitored and evaluated (ICH Q8).

NB：连续工艺验证是传统工艺验证的替代方法，其中持续监控和评估生产工艺性能（ICH Q8）。

Appendix 2: FDA expectations

附录2：FDA期望