首页 > 资讯 > 2015财年一季度仿制药统计数据公布

出自识林

2015-01-30 Lachman CONSULTANTS

编者按 企业付了费，得到了FDA的承诺，从而理直气壮地挑战感受到的（未必是确实的）FDA的不称职行为。大量的ANDA积压、大量的新聘审评和项目管理人员、新的内部协调管理机制、新的外部交流沟通机制、及紧迫的时间线，给FDA带来了前所未有的巨大挑战。一方面，FDA改革创新的勇气、科学态度和开诚精神令人钦佩（例如，按季度，及时地将GDUFA绩效目标完成的情况向社会公布）。另一方面，产业界意见虽然时有尖锐甚至片面，也是监管共治的必要保障。我国药监总局传言中即将启动的类似于GDUFA的收费和审评审批制度改革，也将面临着在短期内招聘和培训大量的审评人员、快速地消化大量的审评积压、同时保障审评的合理及公平性的巨大挑战。识林^TM 希望通过系统地分析报道美国GDUFA的实施情况，为我国未来实施类似的改革提供经验和教训的借鉴。

2015财年第一季度各种运行数据，可以充分表明美国FDA仿制药办公室(OGD)目前的效率水平。众所周知，新雇的审评人员的培训耗费了老审评人员和新审评人员大量的精力；一些亟待解决的重大政策问题也需要人力和时间；OGD启用的新的IT平台有不少问题；来自于不同学科部门有关审评合作的学习曲线是陡峭的；形成ANDA的批准或完全回应函（CRLs）之前需要做大量的工作涉及审评的方方面面。这些都是众所周知的，但根据我的了解，仿制药行业对OGD运行效率不满意，对仿制药收费制度（GDUFA）的热情正在减弱，这可能导致在GDUFA II 期谈判时出现争议。

截至2014年10月，FDA雇用了923名新GDUFA员工（只是这个数字就接近GDUFA之前3倍的OGD员工，是1994年底我离开OGD时OGD员工[155]的6倍）。这些新雇员已在OGD各部门任职。 下面是2015财年头3个月的一些具体数据，以及与2013财年和2014财年的对比。

*- 以2015财年头3个月为代表
**-完全回应函

上面的数据表面了什么？本财年到目前为止CRLs减少了约1/3，与过去两财年第一季度同期相比，减少了超过33%。DMF完整性评估数量有所下降，但这只是一个预期数字，因为新DMF提交或首次审评数量已经于GDUFA第1年和第2年完成。

2015财年一季度原始ANDA接收量大幅度下降。这对OGD来说是好消息。我们没有看到过去通常会发生的12月“大量”提交涌现，因为ANDA提交管道很可能被2014年6月上半月企业因试图避免新稳定性要求的庞大数量的提交而耗尽。从批准这方面看，过去3财年中事情似乎相当稳定，既没有改善。这是难以仿制药行业满意的，这方面OGD必须有很大进步，才能摆脱今年来仿制药申请大量积压的问题。

ANDA申报企业与FDA的受控函数量上与过去两年相持平，表明企业仍有许多问题要问。由于GDUFA对申报企业与FDA交流方式的限制，2015财年的数字可能反映了实际企业药品研发注册问题的增加。

数字毕竟只是评估绩效的一类具体指标，尽管有时可能会误导。我们还应关注从业内同行们那里听到的内容。下面是一些摘录。

• 我们（注册申报人员）对在OGD的提交有很好的记录，通常CRL有大概5-10个缺陷项和小问题。现在我们看到20-40个缺陷项，好像一下子不知道我们是做什么的了。导致企业领导怀疑我们是否称职。
• 我们收到2封只有小问题的CRL，然后意外地，当我们都在期待最终批准时，收到了一封需要重大修订的CRL。
• 我们就一个艰难的ANDA问题反复与FDA沟通已经一段时间了，并认为我们上一封对CRL回复信已经接近解决问题了。然后我们收到一封FDA关于生物缺陷项函的来信，这些缺陷项并没有包括我们在上一封CRL中。FDA说这些缺陷是之前忘了寄给我们，后来想起才寄给我们的。该生物缺陷信还告知在得到进一步的CMC审评意见之前，我们先等候。

这只是过去几个月中我们听到的来自企业界问题中的少数几个。这是OGD成长过程（learning curve）的一部分吗？如果是的话，企业希望OGD赶快完成成长过程。我们常听到的另外一个普遍问题是，自从GDUFA开始，企业就不再知道如果真有难题的话应该打电话给OGD的哪位。项目经理（project manager）似乎每时每刻都在改变，企业不得不等待CRL以查看分配到谁，因为将电话接通非常困难……或者打过去电话，而那边是一位新的项目经理在接听。OGD需要一个更好的方式来找出我们需要与谁对话以便了解ANDA进展情况或解决ANDA存在的问题。

OGD曾经有一个具有专业知识的人员团队，可以解决独特的和意想不到得的问题。现在很新的、缺乏经验的项目经理不知道如何区分ANDA中真正的与表面的问题。如果我有一个愿望，那就是在OGD能有一小部分经验丰富的专业人员可以帮助解决偶尔发生的难题和一次性问题。

Lachman CONSULTANTS - Bob Pollock先生 2015-01-29
编译：识林-椒 2015-01-30
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FY 2015 First Quarter OGD Stats are Published – Picture is Not Rosy
Written by Bob Pollock • January 29, 2015

Well, we now have the actual numbers for various input and output metrics for FY 2015’s 1st quarter that speaks to the current level of productivity at the Office of Generic Drugs (OGD). I know that there are training issues that drain resources for new and existing staff. I know that there are tremendous policy issues that must be addressed. I know that there have been problems with the new IT platform. I know that the learning curve relative to coordination of reviews from the various disciplines is steep and, with the number of moving pieces associated with an ANDA review, it is difficult at best to bring an ANDA approval or Complete Response Letter (CRL) in for a landing. I know all these things, but I also know from the calls I receive that industry is not particularly happy. I also know that, because of these bumps in the road, enthusiasm for GDUFA is waning, which may make for some interesting and contentious negotiations for GDUFA II.

So, let’s look at some of the numbers. FDA has hired 923 new GDUFA employees as of October 2014 (that number alone is close to 3 times the OGD staff pre-GDUFA and that number is also about 6 times the number of staff OGD had [155] when I left OGD at the end of 1994). To be fair, these new employees have been spread out over various components of the Agency, but it also does not include the number of staff already in the programs that contribute to the ANDA review and approval process.

Here are some specific numbers for the first three month of FY 2015 and a comparison to FY 2013 and 2014.

*- Represents first three month of FY 2015
**- Complete Response Letters

So, what do we see so far this FY? CRLs have decreased by about 1/3 so far this FY and, for the first quarter same period over the last three years, it is well over a 33% decrease over same quarter for the last two prior FY. DMF complete assessment numbers have declined, but this is an expected figure since the number of new DMFs submitted or first time reviews have already been completed in year 1 and 2 of GDUFA.

Original ANDA receipts are down substantially over the first quarter FY 2015. This is good news for OGD. There was not the “big” December numbers that we usually see primarily because the pipeline of ANDA submission was likely depleted by the huge number of submissions in the first half of June 2014, as firms sought to beat the new stability requirements. On the approval side of the coin, things seem pretty constant over the last three fiscal years. This is one area where the numbers must be substantially improved if industry is to begin smiling again and if OGD is ever going to get out of the staggering backlog of original ANDAs it has to deal with.

Controlled correspondences seem to be on par with each of the last two years of GDUFA, but the numbers still show that industry has a lot of questions to ask, and now, with the limit on what is classified as a controlled correspondence and who can submit them under the GDUFA metrics, the FY 2015 numbers may actually reflect an increase in actual industry drug development questions.

The numbers are one thing concrete to evaluate performance and, while numbers can sometimes lie, what are we hearing from our colleagues in industry should concern us all. Here are some snippets.

We have had a good record with our submissions at OGD with maybe 5-10 deficiencies and minor status of the CRL. Now we are seeing 20-40 deficiencies and it appears like we all of a sudden don't know what were are doing. Senior management is questioning our effectiveness. We received two CRLs with minor questions, and then out of the blue, when we were expecting final approval, we received a major amendment CRL. We have been working with FDA on a difficult ANDA issue and thought we were circling in on approval based on our last response to a CRL letter, then we got a Biodeficiency letter from FDA that they never got around to sending us (was not in the last CRL) and were told to hold off until we get additional CMC comments. The FDA said whoops we forgot to send the BE comments. These are just a few of the issues we have heard from industry over the last few months. Is this part of the learning curve? If it is, then industry hopes the curve levels out soon. One other general issue that we hear all of the time ever since the inception of GDUFA is that we have no idea who to call at OGD if we have a real problem. The Project Managers (PM) seem to change all of the time and we have to wait for a CRL to see who is assigned because it is so hard to get someone on the phone …or we call and there is a new PM we are instructed to call. There needs to be a better way to find out who we need to speak with to get either ANDA status or an ANDA issue resolved.

Then there is the problem of when something drops through the cracks. Who do you call – certainly not Ghost Busters! But who do you call? There used to be a team of go-to folks that could solve unique and unexpected problems. Now the very new and green PMs are just learning the system and don’t know how to ferret out the real problems from the non-problems. If I had one wish, it would be for a small seasoned go-to force in OGD that can help resolve the hard-to-solve and one-off problems that occasionally arise.

That's enough for today, but if you have similar problems to share I would love to hear about them. Contact me at r.pollock@lachmanconsultants.com or if you or your firm needs help with a problem, contact one of our regulatory specialists at 516-222-6222.