FDA与仿制药企业交流 – 另一种声音
出自识林
FDA与仿制药企业交流 – 另一种声音
笔记 2015-08-23 识林 【编者按】 FDA仿制药办公室（OGD）18日发布的政策和程序手册MaPP5200.3修订版《关于GDUFA第三年之前的简化新药申请与行业的交流》。三天前我们发表资讯，以积极乐观的态度点评了这份文件。今天，我们再来听听来自于业界的另一方观点。 希望能带给大家各方观点，帮助读者明辨式思考。 2014年10月1日之前递交的ANDA被分为两大类。2012年10月1日之前（GDUFA之前）递交的ANDA，其中90%将在2017年9月30日GDUFA I期结束之前被处理。而在GDUFA第1年和第2年递交的ANDA无任何行动日期。2013年OGD发布政策和程序手册MaPP5200解决有关OGD未决ANDA审评中与企业交流的问题。MaPP5200的原始版本遭到了企业的强烈抗议，因为这份MaPP从本质上说就是没有交流，至少是没有有用的交流。2014年10月OGD宣布他们已经听到来自于企业的抗议，将修订MaPP5200。企业持续向FDA施压，要求FDA实现GDUFA中改善与企业交流的承诺，而不是减少与企业的交流。 为什么大家都对一份关于交流的MaPP大惊小怪？是有历史原因在里面的。Hatch-Waxman法案的通过，催生建立了仿制药处（DGD）。法案通过后的一段时期，企业与DGD的交流是自由的，也许太过自由了。ANDA持有人可以自由地在DGD大厅里串门，与审评人员谈论关于他们递交的ANDA的进展情况。换而言之，FDA和ANDA持有人的交流没有任何限制或控制（或记录）。这种无拘无束的交流导致了仿制药丑闻的爆发。尤其是一些审评人员收受贿赂将审评序列中的某些ANDA提前于其它ANDA批准。显然，在企业和FDA之间允许未经核查的交流，为ANDA持有人和审评人员创造了参与犯罪活动以获得竞争优势的环境。继仿制药丑闻之后，FDA严厉打击ANDA持有人和DGD（之后变为仿制药办公室OGD）任何人员之间的所有交流。此后任何交流都是正式的，ANDA持有人申请电话会或会议讨论预先通知的审评问题（而不是审评状态），这些电话会通常会有至少一位审评人员、审评主管以及CSO（Consumer Safety Officer，现在称为项目经理RPM）。这种状态一直持续到GDUFA。作为GDUFA的一部分，企业要求改善交流，尤其是在审评进展方面。以往的回复“正在排队中”，“正在审评中”，几乎总是跟着一句“6个月后再打来电话”，这对于企业在评估实际审评进度或预计可能批准日期以做营销准备方面没有任何帮助。ANDA持有人会认为能够获得批准而花费大量资金在扩大规模、验证和准备销售上，而最后仅得到一个重大增补而不是批准。这将使得许多商业批产品被丢弃而导致大量经济损失。仿制药行业竞争激烈，企业又不可能等到批准后再准备上市，需要在获得批准的第一天就已经做好所有准备。因此，在经历了20年这种不理想的状态后，企业需要一个更好的方案了解自己处于批准过程中的哪个位置。 第一版MaPP5200切断了所有交流！审评状态的良好交流是GDUFA的关键点之一，这种切断所有交流的举动令人非常震惊！所以抗议声异常强烈。之后，FDA改变了之前的意见，并表示会努力制定一个有效的交流体系。现在，几乎接近GDUFA第3年的尾声，我们拿到了修订版本，至少承诺了一些状态交流方案。 然而，FDA已建成的内部交流系统看起来十分脆弱。为了将审评状态信息传递给持有人，似乎有太多的人需要做太多的事情。总之，看起来像是FDA已经建立起一个薄弱的系统，以保证与持有人的交流质量。希望这个系统能够发挥作用，但我并不认为FDA在用心做好与持有人的交流工作。 作者：识林-Pepper Communication with Industry on Pre-GDUFA Year 3 ANDAs ANDAs filed prior to October 1, 2014 fall into two groups. For those filed prior to October 1, 2012 (that is prior to GDUFA), 90% are to be addressed prior to September 30, 2017, the end of GDUFA I. ANDAs filed in GDUFA years 1 and 2 have no action date. In 2013 OGD issued MAPP 5200 which addressed communication with industry regarding review of ANDAs pending at OGD. The original version of MAPP 5200 met with howls of protest from industry since it essentially said there will be no communication, at least no useful communication. In October 2014 OGD announced that they had heard the industry outcry on communications and would revise MAPP 5200. Industry continued to press FDA to live up to the agreement in GDUFA to improve communication with industry, not to reduce it. So why all this fuss about a MAPP on communication? There is history here. In the period following the passage of the Hatch-Waxman Act, which led to the creation of the Division of Generic Drugs, industry communication was free, perhaps too free. ANDA sponsors were free to literally roam the halls of DGD and to talk to reviewers about progress on the review of their filed ANDAs. In other words communication between FDA and ANDA sponsors was not restricted or controlled (or documented) in any way. Well this unfettered communication led to problems that came out in the generic drug scandal. Specifically it turned out that some reviewers were taking bribes to approve ANDAs ahead of their position in the review queue among other things. It was apparent that allowing unchecked communication between industry and FDA created an environment where sponsors and reviewers engaged in criminal behavior to gain a competitive advantage. Following the scandal FDA clamped down hard on all communication between ANDA sponsors and anyone in the DGD (which later became OGD). Any communication was formal, sponsors requesting telephone conferences or meetings to discuss pre-notified review issues (not review status) and these calls always had at least a reviewer, the reviewers supervisor, and the CSO (now called the RPM). This situation continued until GDUFA. As part of GDUFA industry requested improved communication, especially on review progress. The old answer of “it's in the review queue”, “it’s under review” almost always followed by “call back in 6 months” was not helpful in assessing actual progress of review or predicting possible approval dates in order to get ready for marketing. Sponsors would think they were going to get approval and spend large amounts of money on scale up, validation, and preparation for marketing only to get a major amendment instead of an approval. This led to large financial losses as many commercial batches of product were thrown away. The generic industry is highly competitive, you can’t wait for approval before preparing for market, you need to be ready on day 1 of approval. So after 20 years of this unsatisfactory situation, industry wanted a better idea of where they were in the approval process. The first version of MAPP 5200 cut off all communication! Given that better communication on status was a key point in GDUFA, this was astounding! So the outcry was significant. FDA backtracked and said they would try harder to develop a meaningful communication system. The next revision was an improvement but still a far cry from doing what they agreed to do in exchange for the GDUFA money. So now, almost at the end of GDUFA year 3 we have another revision which promises some idea of status at least. However, the system that FDA has built to communicate internally looks fragile. There seem to be too many people who have to do too many things in order to get review status messages to sponsors. In short, it looks like FDA have built a poor system to ensure quality of communication with sponsors. Let us hope it works, but I don't think FDA have their heart in doing a good job of communicating with sponsors. 识林TMwww.shilinx.com版权所有，未经许可不得转载。如需使用请联系admin@shilinx.com Drug Price Competition and Patent Term Restoration Act of 1984 (Hatch-Waxman Act) Mandatory Reading:
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