For induced pluripotent stem cells, if the gene editing is done in a research lab that is not a GMP-like environment to generate a gene-edited clone, which will then be used to produce the GMP-grade master cell banks tested for the cell bank requirements and then differentiated into an iPSC-derived cell therapy products, will that clone be considered acceptable for use in phase 1 clinical studies? Could the same master cell bank be used to produce clinical materials to support phase 2/3 trials as well as to support commercial manufacturing if the product is approved?
对于诱导多能干细胞，如果基因编辑是在非GMP-like环境的研究实验室中进行的，用于产生基因编辑的克隆，然后将用于生产GMP级主细胞库，并按照细胞库的要求进行测试，然后分化为iPSC衍生的细胞治疗产品，该克隆是否被认为可以用于1期临床研究?相同的主细胞库是否可以用于生产2/3期的临床样品，以及如果产品获得批准，是否可以支持商业生产?
Thanks, Steven. We did get a lot of questions about induced pluripotent stem cells. I’m going to hopefully be able to answer a few of them today. We’ll start with this one.
谢谢你,史蒂文。我们收到了很多关于诱导多能干细胞的问题。我希望今天能够回答其中的一些问题。我们从这个开始。
In theory, yes, you may be able to use a clone derived under non-GMP conditions to make a master cell bank under GMP conditions that can be used throughout your clinical development and possibly commercial manufacturing. This is really going to be dependent on whether you can provide sufficient information on the controls that were in place when and where the initial genome editing and cloning was performed.
理论上，是的，你可以使用非GMP条件下的克隆来制造在整个临床开发和可能的商业生产中使用的GMP条件下的主细胞库。这取决于你是否能提供足够的信息，说明在何时何地进行最初的基因组编辑和克隆的控制。
For those who have submitted files, you’ll notice we ask a lot of questions about this. And so we really want to see the quality of the materials, standard procedures, and adequate segregation that was used during those initial steps of editing and to produce that original clone and to test the clone as well. If sufficient information can be provided, then there shouldn’t be an issue with using that clone throughout development.
对于那些提交了文件的人，你会注意到我们问了很多关于这个的问题。所以我们真的很想看到物料质量，标准程序，以及在编辑的最初步骤、产生最初的克隆和测试克隆使用的适当的隔离。如果能够提供足够的信息，那么在整个开发过程中使用克隆就不会有问题。
Kind of as a little caveat I’ll add to this is, I think that sponsors really need to consider whether they’re going to need to perform these steps more than once, whether they think they’re just going to be able to have to manufacture one master cell bank and that’s going to be good to go for their clinical development and for their future commercial as well. If you don’t think so and you think you’re going to have to manufacture more than one master cell bank from multiple different clones or from the same clone, again, these are things that we’ll need to consider when we’re asking for this information as to how many times are you going to have to go back and do these processes during clinical and commercial development. And so those are conversations that we’ll have on a product basis. Thanks, Steven.
我要补充一点，我认为申办方需要考虑他们是否需要不止一次地执行这些步骤，他们是否认为他们只需要制造一个主细胞库，这对他们的临床发展和未来的商业发展都有好处。如果你不这样认为，你认为你将不得不从多个不同的克隆或从同一个克隆中制造多个主细胞库，还有，当我们要求这些信息时，你需要在临床和商业开发中做多少次这些过程是我们需要考虑的事情。这些都是将在产品基础上进行的。谢谢你,史蒂文。