首页 > 资讯 > GDUFA完全回应函与信息请求签发的效率思考

出自识林

2016-03-21 Lachman CONSULTANTS

今年2月是自GDUFA实施以来单月发布完全回应函（CRL）第三高（129封）的月份。之前最高的月份是2015财年7月的134封和2013财年11月的130封。随着审评机器的加速，难道会有人期待着CRL数量每个月稳定增长吗？可能不会！如果信息请求（IR）与易更正缺陷（ECD）持续保持增长，那么CRL的数量可能将保持在较低水平。或者这只是一厢情愿的想法？逻辑上似乎意味着批准数量应该飞升。如果看一下批准行动总数加上CRL的数量，总数实际上一直在增长。因为2016财年的月批准数量增加了。

看一下仿制药计划行动报告2015财年和2016财年的数据，不论如何解读数字，总的迹象是积极的。真正的问题是，在企业满意之前，GDUFA计划需要达到什么程度？我没有答案，但拥有与FDA和仿制药企业相同的希望。

一件非常困扰我的事情是，极低数量的CRL后会议（电话会议）请求。在2016财年的前四个月仅有7次来自企业的此类会议请求（请注意，当查看行动报告时，该处的数字是累积次数而非每月次数，相信该报告的数字是自GDUFA开始累计的。）我想企业对CRL中的问题比起GDUFA开始时有了更深入的理解。或许是因为企业先前已经在申请的IR和ECD中看到了出现在CRL中的大部分问题。也许这就是进步。但请记住，CRL意味着另一轮审评周期，审评周期会导致更长的批准时间。当然我们希望看到更多的首轮批准，但当OGD要求对多晶型或在使用研究中新的研究时，或产生额外的数据，而仅给你10天的时间回复，这基本上是不现实的，也许应该发布CRL。我认为这是企业和仿制药办公室（OGD）需要在更有意义的层面仔细讨论解决的。尽管我们不希望延迟对IR的回复（但要知道，即使有合理的延长，我们也不能满足最后期限），我们也不希望将FDA的资源浪费在发布IR上，仅在10天或20天之后就不得不发布CRL。OGD和企业需要切实地考虑未来的流程效率，更加现实的发布IR可能提高效率的一个方式。我想是时候讨论这个问题了！

Lachman CONSULTANTS - Bob Pollock先生
编译：识林-椒
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Complete Response Letters Reach 3rd Highest Monthly Total Under GDUFA By Bob Pollock | March 20, 2016

February saw the 3rd largest number of Complete Response Letters (CRLS) issued (129) in a single month since the implementation of GDUFA. Previous highs were 134 in July FY 2015 and 130 reached in November FY 2013. With the review machine gearing up, wouldn’t one expect the number of CRLs to be steadily increasing each month? Maybe not! If the information requests (IRs) keep flying out the door along with easily correctable deficiencies (ECDs), then maybe the number of CRLs will remain lower. Or is that wishful thinking? That logic would seem to mean that the number of approvals should be soaring. Well, if you look at the total number of approval actions plus the number of CRLs, the total has actually been going up, and why? Because the number of monthly approvals has increased in FY 2016!

Take a look at the Activities Report of Generic Drug Program Activity for FY 2015 ([here) and FY 2016 ([here) and see for yourself. You can parse the numbers anyway you want but in total these signs are positive. The real question is, where does the program need to be before the industry is happy? I have no answer to that question but have the same hopes as FDA and the rest of the generic pharmaceutical industry.

One thing that does puzzle me is the very low number of requests for post-CRL meetings (teleconferences). In the first four months of FY 1016, there were only 7 such meeting requests from industry (remember, when looking at the Activities Report, the number is cumulative not per month, and it is believed that the numbers reported are from the beginning of GDUFA). I guess that industry has a better understanding of the questions in the CRLs than they did at the beginning of GDUFA. Perhaps that is because they have previously seen most of the questions that eventually appear in a CRL in IRs and ECDs already for the application. Maybe this is progress. But remember that CRLs mean another review cycle and review cycles are what cause longer approval times – they are truly the gift that keeps on giving, according to Dr. Uhl. Sure, we would like to see many more 1st cycle approvals, but when OGD asks for new studies on polymorphs or in use studies, or the generation of additional data and then gives you 10 days to respond, that is basically unrealistic and maybe a CRL should just be issued. This is something I think that industry and the Office of Generic Drugs (OGD) need to hash out in terms of what makes more sense. While we don’t want to delay a response to an IR (but know that we can’t meet the deadline even with a reasonable extension), we also don’t want to waste Agency resources in issuing an IR, just to have to issue a CRL 10 or 20 days later. OGD and industry need to realistically look at ways to further the efficiency of the process and being more realistic in issuing IRs may be one small way to do so. I think it is time that we talk about it!