In both Agencies’ experience, the designspace verification at commercial scale is not necessarily

complete at the time of submission of the applicationbut should occur over the lifecycle of the product and process. Initial designspace verification often occurs solely at or near the target operating ranges.

根据这两个机构的经验，商业规模的设计空间验证不一定在提交申请时完成，但应在产品和工艺的整个生命周期内完成。初始设计空间验证通常仅在目标操作范围内或附近进行。

However, movements from one area to anotherarea within the design space (e.g., re-establishing the Normal Operating Ranges(NOR)) within the approved design space in an unverified area) may pose higheror unknown risks due to potential scale–up effects and/or model assumptions. Itis important that these risks are understood and evaluated utilizing anappropriate control strategy, including but not restricted to the controlssubmitted in the dossier. It is understood that when an applicant demonstratesthat a design space is scale independent, then additional risk mitigation stepsare not necessary for design space verification.

然而，由于潜在的放大效应和/或模型假设，从设计空间内的一个区域到另一个区域的移动（例如，在未经验证区域的批准设计空间内重新建立正常操作范围（NOR））可能会带来更高或未知的风险。重要的是，使用适当的控制策略来理解和评估这些风险，包括但不限于在申请文件中提交的控制。可以理解的是，当申请人证明设计空间不依赖于规模时，则不需要额外的风险缓解步骤来验证设计空间。