20140722 ECA新闻：FDA制订仿制药申报变更处理时限

20140722 ECA新闻：FDA制订仿制药申报变更处理时限2014-08-15 julia翻译 蒲公英
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原文网址：http://www.gmp-compliance.org/en ... 20Applications_8496,8445,S-RGL_n.html

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FDA defines Goal Dates for the Processing of Changes in Generics Authorisation Applications

FDA制订仿制药申报变更处理时限

The FDA recently published a new guideline draft for review. This draft refers to changes in generic drug applications. The document is entitled "ANDA Submissions - Prior Approval Supplements under GDUFA" and describes how the FDA processes Prior Approval Supplements (PAS) in the context of the legal framework GDUFA (Generic Drug User Fee Act) which became effective on 9 July 2012.  GDUFA is based on an agreement that was negotiated by the FDA and representatives of the generics industry. Purpose of this Act is the accelerated processing of generics' authorisation applications to ensure the adequate supply of the population with high-quality, safe and cost-saving generic pharmaceuticals. To finance the required human resources, the FDA has set up a system of fees for the processing of PAS and Drug Master Files (DMFs).  A detailed description of the target agreements in connection with GDUFA can be found in the FDA "Commitment Letter" entitled "Generic Drug User Fee Act Program Performance Goals and Procedures".  

FDA最近公布了一个新的文件审核指南，该指南针对的是仿制药申报的变更。文件名为“ANDA申报—GDUFA框架下的预批准增补”，其中描述了FDA在2012年7月9日生效的GDUFA法律框架下如何处理预批准增补（PAS）。GDUFA是根据FDA与仿制药行业代表谈判的协调建立的，其目的是回事仿制药申报的审核进度，以保证向民众提供充足的高质量、安全和低成本的仿制药品。为了保证所需人力资源的经济基础，FDA建立了PAS和DMF审核收费体制。在FDA题为“仿制药用户收费法规项目的实施目标和流程”的“承诺信”中，可以看到GDUFA相关的协议的详细情况。

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The Guidance sets two time periods for processing Prior Approval Supplements (PAS):

指南中设定了处理PAS的两个时间限

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6 months if no inspection is required  

6个月：如果不需要进行现场检查

10 months, if an external inspection has to be conducted

10个月：如果需要进行外部检查

The period begins on the day on which the PAS was submitted via the electronic FDA portal.  The 10-month period may be shortened to six months if the authority subsequently determines that no inspection is necessary.

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计时起始点为通过FDA的电子端口上传PAS的日期。如果药监部门之后认为不需要进行现场检查，则时间会缩短为6个月。

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Another category of documents for which the FDA has fixed specific goal dates for processing are amendments to marketing authorisation applications (ANDAs) or to PASs. These amendments are response letters which the applicant obtained following the authority's deficiency letter - the so-called "complete response letter". For the processing of these amendments, the FDA has further published a guidance entitled "ANDA Submissions - Amendments and Easily Correctable deficiencies under GDUFA". This Guideline draft describes in great detail the handling of the different types of amendments and their review times.  Amendments are divided into three main categories and several subcategories:

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FDA将文件进行了分类，为上市许可申报（ANDA）和PAS的处理设定了不同的目标时间，还有一些增补是申报者在收到药监局的缺陷信（所谓“完整回复信”）后所做的回复。FDA为这样的增补公布了另一份题为“ANDA申报---GDUFA下增补和容易修改的缺陷”的指南。该指南草稿详细描述了对不同类别增补的处理及审核所需时间。增补被分为三个主类和几个子类。

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Solicited Amendment

- Major amendment (e.g. new analytical methods, new bioequivalence studies, new validation methods)

- Minor amendments (e.g. small changes to a validated method of analysis, additional stability data)

- Easily correctable deficiency (e.g. lack of information which, however, the applicant has available; misplacement of information in the amendment  

主动增补

--重要增补（例如，新分析方法、新的生物等效性研究、新的验证方法）

--一般增补（例如，对已验证的分析方法的轻微变更、增加稳定性数据）

--容易修改的缺陷（例如，申报资料缺失，但申报者实际拥有这些资料，增补中资料放错了位置）

Unsolicited  Amendment

- Delaying amendment (actions of third parties which the applicant has no control of, such as the revision of a monograph by the USP)

- Nondelaying  amendment (unsolicited submission of new data, for example on a new strength of the drug or with regard to a new production site)  

被动增补

--滞后增补（第三方行为，申报者无法控制，例如USP各论修订）

--非滞后增补（新数据，例如新的剂量的药品或新的生产场所）

Administrative Amendments (general correspondence with the authority which is not subject to review, and does not affect the goal dates)

行政增补（与药监局的常规信件往来不需要经过审核，不影响目标日期）

For the major and minor amendments as well as for the easily correctable deficiencies the Guidance's Annexes A to C each provide a number of concrete examples.

对于重要增补、一般增补和容易修改的缺陷，在指南的附录A至C中分别提供了一定数量具体的例子。

The various amendments are then processed in a three-level tier system, in which different amendment types and goal dates are assigned to each tier. Annex D of the Guidance contains a flowchart of the various amendments associated with the system.

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不同的增补就这样按三级分布系统进行处理，在不同的级别中，给定了不同的增补类型和目标日期。指南附录D中有一张不同增补及其体系的流程图。

It should be noted that the review times may add up. That means that an original goal date for the processing of a PAS may be extended, depending on the type of amendment submitted in the meantime. To this end, the Guidance "Prior Approval Supplements and GDUFA" lists some examples.

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要注意的是，根据同时提交的增补的类型情况，审核时间可能会加和，也就是说初次订立的处理PAS的目标时间可能会延长。关于该延长时间，指南“预批准增补和GDUFA”中列出了一些案例。

The 3-tier system for the processing of amendments is quite complex and yet can lead to unforeseen delays in spite of defined review times. In the approval process applicants should seek to keep the number of amendments as low as possible by submitting high-quality applications in order to rapidly obtain the authorisation and also to save fees.

处理增补的3层体系很复杂，尽管界定了审核时间，但仍可能会导致不可预期的延迟。在批准过程中，申报人应尽量通过提交申报资料的质量而使增补次数保持最少，以尽快获得批准，同时节省费用。

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The goal dates for PASs described in the two Guidances will become effective on 1 October 2014. The procedures / goal dates for amendments will only be applicable to those referring to authorisation applications (ANDAs) on 1 October 2014 or thereafter. Therefore, the generics industry remains some time to adjust to the new regulations.

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在两个指南中给定的PAS目标时间将于2014年10月1日生效。增补审核的流程/目标日期将只适用于2014年10月1日起（含）所提交的申报（ANDA），因此仿制药行业还有一些时间做出调整来适应新法规。

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