Q:In light of technical and logistical challenges specific to autologous cell-based gene therapies, what is the expectation on formal process characterization? For example, design of experiment type studies?
鉴于以自体细胞为基础的基因疗法所特有的技术和后勤挑战，对正式过程描述的期望是什么?例如，实验类型研究的设计?
A:I do expect that process characterization studies are conducted to find manufacturing process for autologous cell-based gene therapies.
我希望进行工艺表征研究，以找到基于自体细胞的基因疗法的制造工艺。
In most cases, it is appropriate to show that the healthy donor material is representative of the patient’s specific process. And then you can use healthy donor material for these process development studies. And this generally allows for you to explore a wide range of different parameters within the process in order to understand how they affect your manufacturing process. And this can allow you to define the parameters for your commercial process for it to be successful and more consistent when using the autologous starting material.
在大多数情况下，证明健康的供体材料代表患者的特定过程是适当的。然后你可以使用健康的供体材料进行这些工艺开发研究。这通常允许你探索工艺中不同参数的宽的范围，以了解它们如何影响你的制造过程。这可以让你为你的商业工艺的成功去定义参数并且在使用自体的起始物料时更加稳定。
We do understand that there may be some instances, particularly when the introduced gene replaces a missing gene, but not all attributes may be tested in products manufactured using a healthy donor material. This is most often encountered, for instance, with potency testing. But there are other aspects to the manufacturing process that may be affected.
我们确实理解可能会有一些情况，特别是当引入的基因取代缺失的基因时，但并非所有属性都可以在使用健康供体材料制造的产品中进行测试。这是最常遇到的，例如，效价测试。但制造工艺的其他方面可能会受到影响。
And so in this case, we would recommend that you should evaluate some small-scale manufacturing studies and see if those can be used to support manufacturing process characterization and allow you to gain the necessary information while maximizing the use of patient-derived starting material. And in these specific cases, it may be beneficial to discuss such limitations with your FDA review team prior to initiating these critical studies.
所以在这种情况下，我们建议你应该评估一些小规模的生产研究看看这些研究是否可以用来支持生产工艺的描述并允许你获得必要的信息同时最大限度地使用患者来源的起始物料。在这些特定情况下，在开始这些关键研究之前，与FDA审查小组讨论这些限制可能是有益的。