Q:What is the current thinking about drug compatibility related to delivery devices? In general, would the same acceptance criteria as lot release of the drug product be sufficient for drug compatibility? Dose the OTAT consider human factors in using delivery devices?
目前关于给药装置有关的药物相容性的想法是什么?一般来说，与药品批放行相同的可接受标准是否足以满足药物相容性要求?OTAT在使用给药装置方面是否考虑人为因素?
A:Thanks,Steven, and welcome, everybody. The main goal for device/biologic compatibility is to demonstrate that administering the drug product using the delivery device won’t negatively affect the product’s quality and then also that you understand the quality of the product that will actually be delivered to the patient.
谢谢Steven，欢迎各位。设备/生物相容性的主要目标是证明使用给药设备给药不会对产品质量产生负面影响，然后你也了解实际交付给患者的产品质量。
Compatibility studies should be collected with the final formulated drug product under the worstcase conditions expected in the clinical trial. That includes, say, thaw conditions, any dose preparation procedures, duration of storage after preparation, your dose or volume range, a flow rate or pressure, duration of delivery, the temperature, the simulated delivery into the worstcase target tissue anatomy, and other things as applicable as far as risk assessment that’s performed to what could potentially affect the compatibility of the drug product with the device.
应临床试验预期的最坏情况下，收集与最终配制药品的相容性研究。这包括，解冻条件，任何剂量制备程序，制备后的储存时间，剂量或体积范围，流速或压力，输送持续时间，温度，模拟输送到最坏情况下的目标组织解剖，以及其他适用的风险评估，这些评估可能会影响药物产品与器械的相容性。
For vectors, you really want to know if there’s any vector adsorption to the device, so you’d think about evaluating your vector titer, so whether it’s genome or infectious titer, before and after exposure to the device, or any effect on vector activity — for example, measuring your transgene expression or performing your potency assay before and after exposure to the device.
对于载体，你真的想知道是否有任何载体吸附到器械上，所以你会考虑评估你的载体效价，无论是基因组还是感染效价，在暴露于器械之前和之后，或者对载体活性的任何影响-例如，测量你的转基因表达或在暴露于设备之前和之后进行你的效力测定。
The compatibility data really should inform and instruct the instructions for product handling that’s provided to the pharmacy as well as the clinical administration site.
相容性数据确实应该告知和指导提供给药房和临床管理场所的产品处理说明。
As far as using the same acceptance criteria as lot release for your drug product for the device compatibility study, this is really going to depend on how wide the lot release acceptance criteria are. While the product should meet the lot release acceptance criteria following passage through the delivery device, it may be better to establish acceptance criteria for how much product loss is actually acceptable for you to still maintain your product quality and your intended product dose.
至于在器械相容性研究中使用与药品批号放行相同的验收标准，这实际上取决于批号放行验收标准的范围。虽然产品在通过给药器械后应满足批次放行验收标准，但为了保持产品质量和预期产品剂量，最好建立验收标准以确定产品损失的实际可接受程度。
Regarding human factors testing, yes, we do work with the Human Factors group here at FDA when warranted. We generally will request a human factor study to be performed on the delivery device if there are special circumstances involving the actual use of the device or if it’s a very specific use of a device. And so for that, like I said, we consult with the group here that specializes in human factor studies. And so that should definitely be discussed early on with the FDA team if you believe there is going to be a need or whether we infer that there’ll be a need for a human factor study. We’ll discuss that early with the sponsors as well. Thanks, Steven.
关于人为因素测试，是的，我们在必要时与FDA的人为因素小组合作。如果有特殊情况涉及到设备的实际使用，或者是设备的特殊使用，我们通常会要求对交付设备进行人为因素研究。因此，就像我说的，我们咨询了这里专门从事人为因素研究的小组。所以如果你认为有必要或者我们推断有必要进行人为因素研究那么一定要尽早与FDA小组进行讨论。我们也会尽早和主办单位讨论这个问题。谢谢你,史蒂文。