首页 > 资讯 > 完全回应函、信息请求、易更正缺陷函与批准

出自识林

2015-10-20 Lachman CONSULTANTS

完全回应函（CRL），是FDA将所有处级审评一次性回应给申请人的的函件，并且申请人不会获得任何更多的具体学科信。完全回应函是“批准问题太多而无法通过其它方式解决”的预兆。因此，如果问题复杂或太伤脑筋而无法批准的话，只能指望得到一封完全回应函了。

信息请求（IR）和易更正缺陷（ECD）函。OGD听取了企业的意见，已经认识到实时审评的新药模型和关于申请的与问题相关的交流，可能更有助于驱动申请获批。因此，IR和ECD更像是迷你的具体学科审评，使得ANDA申请持续通过该系统，并有希望更快获批。这些函件也给了企业时间在审评过程的早期回复突出问题，使企业整体受益，尤其是，如果那些尚未完成审评的学科在递交过程中没有发现问题。因此可以在计时方面助企业一臂之力。

这听起来不像过去的仿制药办公室了？在一定程度上是的，但现在协调工作还需更多磨练，希望随着与IR和ECD相关的审评和回应次数的明确，流程运行能更加顺畅。

从一些新的统计数据中发现的批准数量缓慢攀升而CRL的数量出现滞后，其原因变得越来越清楚：OGD努力的重点是保持申请在批准的轨道上前进，而不是签发CRL。此外，对于一封IR和ECD实际上代表了什么的困惑，难倒了许多企业。现在，我们知道，你可能会从任何一个学科中接收到IR或ECD，因此不要以为你从质量工作组接到了一封ECD或IR，你的标签、微生物、生物等效性或合规状态就是可接受的。你可能会受到多封“临时的”信息请求。

现在来看看2015财年可能从签发CRL方面转移过来的一些工作量，截至2015财年8月31日OGD签发4276封IR和ECD（九月份的数据尚未给出），约1000封CRL。因此，投入到签发批准和CRL的许多努力“暂时”转向了实时签发IR和ECD。OGD相信这将转化为较大数量的批准，从而降低签发CRL的需求。

或许会觉得这有些迟钝，可能在批准量真正激增之前令人有所怀疑，但是想想看，其实这是非常有意义的。新药部门使用相似的系统已达到85%的首轮获批率，而OGD仅有不超过3%的首轮获批率。让我们等待2016财年的数字吧。另外，如果收到IR和ECD请尽快回复给OGD。

Lachman CONSULTANTS - Bob Pollock先生 2015-10-18
编译：识林-椒
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The Ying and Yang – CRLs vs IRs ECDs and Approvals
By Bob Pollock | October 18, 2015

As they say, “you learn something new every day”! Perhaps I knew this all along but I had my suspicions confirmed yesterday. So what is it that I learned? That Complete Response Letters (CRLs) (remember those letters where FDA was going to respond all at once with Division level review and you were not going to get any more discipline specific letters?) are a harbinger of “approval issues that are too great to resolve through other means”. Yes, that’s right, expect a CRL if issues are complex or too vexing to permit approval.

Now what about Information Requests (IRs) and Easily Correctible Deficiency (ECDs) letters? Well, OGD has listened to the industry, and has recognized that the New Drugs model of real time review and communication relative to issues regarding the application may work better in driving the application towards approval. Thus, the IRs and ECDs are more like mini discipline-specific reviews that will allow the ANDA application to continue moving through the system and hopefully towards approval faster. These correspondences also give the industry time to response to outstanding issues earlier in the review process and will benefit the firms overall, especially if other disciplines that have not yet completed their reviews find no problems in the submission. Thus, it gives the industry a leg up in the timing department.

Doesn’t this sound like the Office of Generic Drugs (OGD) of old? Well, yes to some extent, but now that the coordination efforts are more honed, hopefully the process will run smoother with defined review and response times that are associated with the IRs and ECDs.

In looking at some new statistics, it is becoming more clear that the reason the numbers of approvals are slowly creeping up while the number of CRLs has appeared to lag is that the body of effort expended by OGD to keep the application on track for approval rather than a CRL has maybe not been as obvious to industry. In addition, confusion about what an IR and ECD actually represent has baffled many on the industry side. Now we know that you may get an IR or ECD from each of the disciplines, so don’t think that because you get an ECD or IR from the quality group, that your labeling, micro, bioequivalence or compliance status is acceptable. You may get multiple “interim” request for information.

Just to give you an idea of the workload that may have been diverted from issuance of CRLs in FY 2015, OGD issued 4276 IRs and ECDs in FY 2015 through August 31 (September figures are not yet in) and about 1000 CRLs. Thus much of the effort that goes into issuance of approvals and CRLs have been shifted “temporarily” to real time issuance of IRs and ECDs. OGD believes that this will translate into a larger number of approvals and thus a lower need to issue CRLs.

I know that this might be a bit obtuse and recognize that you may be skeptical before the approval numbers really shoot up, but when you think about it, it makes perfect sense. The New Drugs folks have about an 85% first cycle approval rate using a similar system, whereas OGD has less than a 3% first cycle approval rate. Let’s take a look at how that number fares in FY 2016. Please remind me if I forget! Oh and yes – get those IR and ECD responses back into OGD quickly!