首页 > 资讯 > Boehm博士谈GDUFA两重要指南草案

出自识林

2014-07-13 识林

本周四（2014年7月10日），FDA发布两份重要指南草案解决GDUFA绩效指标相关的某些方面问题。这两份指南草案是：
ANDA提交—GDUFA下增补和易更正缺陷(ECDs)
ANDA提交—GDUFA下的补充申请

需要注意的是这两份指南草案仅适用于2014年9月30日之后提交的ANDA或之前已获批申请的补充申请。这些将是处于GDUFA绩效指标下的首批ANDA和PAS。

因为在该日期之后，FDA必须满足ANDA和PAS提交的时间限，需要考虑增补和缺陷显然会影响FDA满足时间限的能力。GUDFA的设计是为了大力鼓励申请人提交高质量、完整的ANDA和PAS，而“惩罚”那些需要修订或有缺陷的ANDA和PAS。缺陷越是显著，延长审评时间的惩罚越是严厉。指南草案详细说明了由于提交后缺陷或增补导致的审评时间的变化。

第一份指南草案涉及原始ANDA的增补和缺陷问题。这是一个复杂的话题，不花大量的时间和努力来描述GDUFA承诺函中的“层级”系统是非常困难的。此外，虽然设定了缺陷状态，但并不代表什么缺陷会被认为是重大缺陷、微小缺陷或“易更正”缺陷。这种情况下，该指南草案的附录中给出的例子非常有帮助。GDUFA之前的重大缺陷是任何需要提交新的申报批或新的生物等效或临床研究的缺陷。指南草案中给出了35个重大缺陷的例子，这并不是一个详尽的清单。但总的来说，是非常有帮助的一份指南。

第二份指南草案考虑了GDUFA绩效指标下的PAS提交问题。这份指南草案涉及GDUFA下需要缴纳使用者费的已获批申请的补充申请，同时通过了在提交以及任何增补和缺陷方面处于“层级”系统中的与新ANDA类似的流程。 这在指南草案中均有解释，且非常清楚。一件PAS是否需要检查对于PAS的审评时间是非常重要的问题，指南草案中提出一些情形解释检查需求在补充申请提交时并不总是显而易见的。在另外的情形下，可能产生覆盖多件PAS提交的检查。

这两份指南草案均对承诺函中规定的绩效指标提供了大量解释。FDA网站上有针对这两份指南草案分别做出解释的幻灯片和网络会议（请见此处）。幻灯片写的非常好，提出并添加了许多对指南的理解。有趣的是，两个幻灯片均由OGD的两位法学博士（J.D.）撰写。或许这是在GDUFA的世界未来会发生什么的一个预示。【2015年8月18日，CDER发布了MAPP 5200.3修订版《关于GDUFA第三年之前的简化新药申请与行业的交流》， 参见FDA将在与仿制药企业交流与透明度方面大为改进 识林资讯 2015-08-20】

北京大学药物信息与工程研究中心 - Garth Boehm博士 2014-07-12
校译：识林-椒 2014-07-12

Changes to a Pending ANDA and Prior Approval Supplements under GDUFA
Written by Garth Boehm • July 12, 2014

Last Thursday (July 10, 2014), FDA published two important draft Guidances addressing some aspects of GDUFA performance goals related issues. These two draft Guidances are:
ANDA Submissions – Amendments and Easily Correctable Deficiencies under GDUFA
ANDA Submissions – Prior Approval Supplements under GDUFA

It is important to note that these draft Guidances apply ONLY to ANDAs or Prior Approval Supplements FILED AFTER September 30, 2014. These will be the first ANDAs and PAS subject to GDUFA FDA Performance Goals.

Because FDA has to meet certain timelines for ANDAs and PAS filed after this date, the goals have to take into account amendments and deficiencies since these actions obviously affect FDA's ability to meet the timelines. The design of GDUFA is intended to strongly encourage sponsors to submit high quality, complete ANDAs and PASs and so "punishes" the need to amend or get deficiencies, the more significant the deficiencies the stronger the extended review time punishment. These draft Guidances detail the review timing changes that result from post filing deficiencies or amendments.

The first draft Guidance addresses the issue of amendments and deficiencies for original ANDAs. This is a complex topic and the description of the "tier" system in the GDUFA Commitment Letter is difficult to follow without a lot of time and effort. In addition, while setting conditions for deficiencies, it does not indicate what will be considered a major deficiency, a minor deficiency or an "easily correctable" deficiency. The draft Guidance gives examples of these in the Appendices which is very helpful. Note however that the definition of a major amendment has expanded considerably. Pre-GDUFA a major deficiency was anything that required the submission of new exhibit batch(es) or a new bioequivalence or clinical study. The examples of major deficiencies given in the draft Guidance number 35, and this is not an exhaustive list. Overall this is a very helpful draft Guidance.

The second draft Guidance concerns filing of PASs under GDUFA's FDA performance goals. This draft Guidance addresses Prior Approval Supplements, which require user fees under GDUFA and go through a similar process to new ANDAs in terms of filing and any amendments and deficiencies are also subject to a "tier" system. This is all explained in the draft Guidance and is quite clear. The issue of whether a PAS needs an inspection is a significant issue for PAS review timing and some situations are laid out in the draft Guidance to explain that inspectional requirements may not always be apparent at the time of supplement filing. In addition situations that could generate multiple PAS filings are covered.

Both these draft Guidances offer a lot of clarification of the performance requirements laid out in the Commitment Letter. They are each accompanied by a slide presentation which explains the Guidances and by a "webinar" which also explains the material in the Guidances ( Here ). The slide presentations are very well written and presented and add a lot to the understanding of these Guidances. It is interesting to note that both slide presentations were written by OGD staff members who are JDs. Perhaps this an indication of what the future holds in the GDUFA world!

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