RTR指南草案发布
出自识林
RTR指南草案发布
笔记 2013-10-03 FDA,Lachman CONSULTANTS 2015年,美国FDA的ANDA拒收指南修订版,请查看ANDA申请提交拒收指南定稿修订2015(2015.05.28) 概述 企业如何看呢?对于企业,尤其是海外企业,最大的挑战是留给企业的缺陷回复时间。ANDA缺陷由FDA通过美国代理人联系到企业的时间通常是2-3天,FDA从电话联系代理人的那一刻开始计时。如果涉及到第三方和签字,并且如果签字人(通常是大老板)不在,交流是最大的挑战。例如,某个缺陷涉及到包装材料(玻璃瓶或瓶盖和胶塞、着色剂、瓶盖衬垫和密封垫等)的DMF授权信(LoA)。理论上LoA应交给ANDA持有人而不是药品生产商(有时两者是不一样的),但是玻璃瓶供应商没有联系ANDA持有人,他们将玻璃瓶卖给药品生产商,因此LoA是交给生产商的。持有人提交ANDA时,如果FDA要求DMF LoA交给ANDA持有人,这将涉及第三方交流。ANDA持有人没有办法在第5天结束时将回复放在审评人的办公桌上。eCTD/ESG电子提交有时也会出现问题,如果出现问题,可能会拖延整个过程。另外,每次提交都需要FDA 356h表,现在需要企业负责办公室和美国代理人共同签署,正反面签署356h表格同样花费时间,更不要说可能会出错。过去企业的缺陷回复时间是10天,根据企业实践,已经比较紧张,而现在缩短到5天,这对于企业的压力非常大。企业抱怨道,当我们付清了所有费用,FDA却开始让ANDA申请变的更加困难! 不管怎么样,紧跟上周发布的关于“未决申请问询的MAPP”【识林资讯 2013-9-26】接踵而至的这份指南这可能是一件好事。随着越来越多的GDUFA措施的落实,包括MAPP和拒收指南,我们饶有兴趣的等待随之而来的是ANDA质量的提高还是问题依然存在? 识林-椒 2013-10-3 Time to Tighten Your Belts and Pay Attention to Quality Written by Bob Pollock • October 01, 2013 Over the years, OGD has issued Completeness and Acceptability checklists in an effort to make ANDA applicants aware of the latest requirements for submission. In addition, OGD often holds joint meeting with GPhA to provide industry with the most recent information necessary to file complete applications. All of these efforts have been undertaken to improve the efficiency of the ANDA review and approval process. The goal is to have the most complete application submitted, and thus, making the review of the application, hopefully, a one or two cycle process. You send OGD the application, they tell you what is wrong with it, and then fix it. Thse meeting and exchanges are essential for successful submissions. Unfortunately, history really does repeat itself. The first series of letters and advice to industry relative to the need to submit a complete application was to level the playing field and assure that every firm was doing the necessary work to submit a complete application, as many firms were just trying to get something into the Agency to get the clock started or to try to capture the first-to-file place in line. Well now we are right back to where we were in the late 80s when firms tried get the clock started by submitting an ANDA that might not quite be what they really want in terms of potential conditions of marketing. For instance, a firm may submit an application with one source of API, but really want to use another. They may not really want to commercialize a product from the filed manufacturing site or they may want to use a different contract packager for commercial operations. GUDFA takes care of that to a certain extent by adding review time penalties for major and multiple minor amendments to the application. But the question of what gets you in the door first still matters. On September 30, 2013, OGD issued a draft guidance for industry entitled, ANDA Submissions – Refuse-to-Receive (RTR) Standards, that outlines how your application will be evaluated for receipt purposes. The Guidance divides deficiencies into major (for which a RTR will automatically be triggered) and minor (for which you may have 5 days to correct) categories for the completeness and acceptability review process. Have 1 major or 10 or more minor deficiencies and your application will not be received. Penalty for such a determination is a loss of 25% of the ANDA user fee. The guidance document (here) discusses the RTR history over the last four year where OGD has RTRed some 497 ANDAs with the % of RTRs actually falling from 18% in 2010, to 15.5% in 2011, and 9.4% in 2012 (however, the 2012 figures are based on incomplete data, given many of the ANDA submitted in 2012 have not yet completed their completeness and acceptability review). Most of the 100 RTR letters in 2012 fell into one of three categories, serious bioequivalence issues accounting for 40%, 36% for serious chemistry issues, and 13% for format or organizational flaws. The 9/30/13 guidance will likely result in an initial increase in the rate of RTR letters for 2013 submissions. This will likely be compounded by the upcoming increase in stability requirements to take effect in June of 2013; however, at least firms are now on notice about current expectations. In addition, OGD updates its ANDA checklist quarterly to capture new areas of concern and focus. The most recent ANDA checklist for Quarter 2 of 2013 can be found here. 原文请见 Time to Tighten Your Belts and Pay Attention to Quality 2013-10-1 |