首页 > 资讯 > FDA 505(q)请愿年度报告及对相关申请的影响

出自识林

2015-09-28 Lachman CONSULTANTS

FDA需要每年向国会报告前一年认定为505(q)请愿的请愿数量和505(q)请愿对505(b)(2)申请、ANDA或生物类似药申请的批准延迟数量。

FDA报告中指出，在过去一年中（2014年），实际上仅1份505(q)请愿延迟了一件505(b)(2)NDA的批准。2014财年共102份请愿提交到FDA，其中，28份被定性为505(q)请愿。那么，如果仅一份请愿延迟了任一申请的批准，会有什么问题呢？FDA关注的是那些专门用于回应请愿的资源，可能能够更好的用于申请审评。下面的表格来自于FDA报告 ，描述了请愿数量、请愿结果和因请愿导致的延迟（如果有）。

许多请愿被完全拒绝（过去7年中超过98份），仅8份请愿获得完全准许，39份请愿部分准许部分拒绝。通常，那些获得准许或部分准许部分拒绝的请愿中，许多准许代表请愿者要求的，FDA无论如何也都会要求。例如，包含对餐后研究要求的请愿，FDA的标准实践对于该类产品也要求餐后研究。有一些请愿FDA超出正常需要的要求，可能是请愿者成功论证了安全性或有效性的要求的情况。例如，当原研者已成功证明在药效学响应方面的临床显著差异，实际pK曲线与原研药不一致，请愿包含可能需要局部AUC以更好的界定药物动力学曲线用于建立生物等效。

过去7年中，FDA一直在跟踪这些请愿类型，一份505(q)请愿已推迟批准7件ANDA和一件505(b)(2)申请。当考虑到这期间递交到FDA的ANDA和505(b)(2)申请数量时，这个数字似乎相当小。然而，许多请愿者递交系列请愿，例如，随着时间的推移针对同一基本问题的充满波折的多份请愿，导致了大量的FDA的努力，影响稀缺资源的使用。此外，FDA指出，FDASIA通过将法定响应时间从180天缩短至150天，增加对FDA资源的压力。

所以，这一切的一切，尽管505(q)请愿数量看起来不多，FDA仍担心505(q)过程没有阻止这些可能不是所有都具有科学价值的请愿的递交。FDA还担心法律规定在150天的时间框架内回复这些复杂请愿的资源需求。有趣的是，尽管法律授权FDA立刻拒绝505(q)请愿，如果FDA确定请愿仅仅旨在推迟ANDA、505(b)(2)、NDA或生物类似药申请的批准，但FDA从未（根据报告）使用 FDASIA的这一规定。

Lachman CONSULTANTS - Bob Pollock先生
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Annual Report of 505(q) Petitions and Impact on the Delay of Associated Applications
By Bob Pollock | September 28, 2015

The FDA is required to produce a yearly report that addresses the number of petitions filed during the previous year, the number of those petitions that were designated as 505(q) petitions, and the number of the 505(q) petitions that delayed whether a 505(b)(2) application, ANDA or biosimilar approval.

The FDA report (here) indicates that, during the previous year period (2014), only one 505(q) petition actually delayed the approval of one application (a 505(b)(2) NDA). There were 102 petitions submitted to FDA in FY 2014; of those, 28 were characterized as 505(q) petitions. So what’s the problem if only one petition delayed the approval of any application? Well, FDA is concerned about the resources that are devoted to responding to the petitions that could have been better spent reviewing applications The following tables come from the FDA report and describe the numbers of petitions, outcomes of petitions and delays caused by the petitions (if any).

Many petitions are denied outright (98 over the 7-year period), only 8 were fully granted, and 39 were granted in part and denied in part. Typically, of those petitions that have been granted or granted in part and denied in part, many of the grants represent requests by petitioners to do what the FDA would have required anyway. For example, the inclusion of a requirement for a fed study where the standard practice would be for the FDA to require a fed study for that type of product. There are some petitions where FDA goes beyond requiring normal requirements, as may be the case when a petitioner successfully argues for a safety or efficacy requirement. For example, where the inclusion of a partial AUC may be required to better define the pharmacokinetic curve for establishing bioequivalence, when the innovator has successfully demonstrated a clinically significant difference in pharmacodynamics response should the actual pK curve not match that of the innovator.

Over the 7 years FDA has been tracking these types of petitions, a 505(q) petition has delayed the approval of 7 ANDAs and only one 505(b)(2) application. This may seem fairly small when considering the number of ANDA and 505(b)(2) applications that have been submitted to the Agency over this time period; however, many petitioners submit serial petitions, e.g., multiple petitions over time that address the same basic issue with new twists that result in a substantial FDA effort, which compounds the impact on the use of scare resources. In addition, FDA notes that FDASIA has increased the strain on Agency resources by shortening the statutory response time from 180 says to 150 days.

So, all in all, while the numbers of 505(q) petition does not seem that large, FDA is still concerned that the 505(q) process is not discouraging the submission of these petitions that may not all have scientific merit, which it was designed to do. And FDA remains worried about the resources required to respond to these complex petitions within the 150-day time frame required by the statute. Interestingly enough, although the statute does give the Agency authority to deny a 505(q) petition straight away if the Agency determines that the petition is solely designed to delay the approval of an ANDA, 505(b)(2) NDA, or a biosimilar application, the FDA has never (according to the report) utilized this provision of FDASIA.