2014-01-28 Lachman CONSULTANTS
仿制药办公室征询关于如何改善简化新药申请的意见
在2014年1月23日公布的联邦公告中，仿制药办公室征询关于如何改善递交的简化新药申请（ANDA）质量以及此类申请相关修订的意见与建议。此外，仿制药办公室也在询问企业在准备简化新药申请中所遇到的具体困难，以便FDA可能 为业界“提供更多或更好的信息”。
FDA正采取行动，试图通过在最初提交申请时接受更高质量与更为完备的申请来加速仿制药申请上市。 FDA指出，《仿制药生产商付费法案》（Generic Drug User Fee Act, GDUFA）给仿制药办公室审评简化新药申请制订了明确标准，但是FDA表示，该部门正“受到简化新药申请质量困扰”。
在FDA征询建议的同时，他们也在希望征询如何最好地将这些建议与业界分享的思路。FDA将在公告公布于 FDA-2014-N-0032文件后的60天内征询相关意见。 该公告罗列了在化学生产与控制、生物等效性、灭菌保证、Form 356h所列问题、药物主文件中常见的缺陷类型，以及在简化新药申请中发现的“致命缺陷”。 FDA正就以下类型问题中的一类或几类征询意见与建议：
1. 简化新药申请流程的哪些方面是混乱的或未明确规定？
2. FDA可以帮助改善 在简化新药申请申请者提出一份申请时面对的哪些问题？
3. 在仿制药生产商付费法案之前，是否提交简化新药申请一直以来在特定的审评节点中经常性出现放缓或停顿？如果这样，原因何在？
4. 除发布监管指南外，FDA应怎样与业界分享关于改善简化新药申请的建议？
仿制药办公室审评流程未曾解决的问题之一（不仅自仿制药生产商付费法案之后，也自 Hatch-Waxman 法案公布之后），是仿制药办公室审评一致性的问题。尽管业界的简化新药申请可能需要提高质量，FDA难以得到优质申请的一个原因是，历史上，简化新药申请的申请者一直试图基于过去的经验，即针对收到的仿制药办公室就其它申请指出的缺陷而作出回应，修改其它申请。 但是，鉴于审评员或者具体部门不同，传统上审评往往大为不同。许多公司认为，他们长期以来试图追逐的目标其实是不固定的。当企业的申请对一些质量缺陷确实负有责任的同时，审评机构也需对其审评的一致性担负一定责任，而业界正是从这些审评中，了解到审评机构的期望到底是什么。对于相同企业的类似申请，在申请内容在本质上相同的情况下，收到了截然不同的完全回应函（Complete Response Letters, CRLs）或缺陷函，或者一份简化新药申请收到拒收函，而来自于同一企业另一份不同规格的非常类似的申请（特别立卷考虑）被接受审评，有很多这样的例子。
对于审评与批准流程中困扰业界与监管机构审评与审批流程的问题，请务必给出您的意见与建议，这将增加对相应问题的透明度与深入了解。
Lachman CONSULTANTS - Bob Pollock先生 2014-01-22
校译：识林-Kapok 2014-01-27
OGD Seeking Comments on How to Improve ANDAs
Written by Bob Pollock • January 22, 2014
In a Federal Register Notice to publish on January 23, 2014, OGD is seeking comments and suggestions on how to improve the quality of submitted ANDAs and associated amendments to those applications. In addition, OGD is asking about what specific difficulties firms are having when preparing their ANDAs, so that FDA might help “provid[e] more or better information” to industry.
FDA is taking this action in an attempt to help speed generic applications to market by receiving higher quality and complete applications at the time of initial submission. The Agency notes that the Generic Drug User Fee Act (GDUFA) places definitive metrics on OGD relative to review of ANDAs, but FDA says they are being “hampered by the quality of ANDA submissions”.
While the Agency is seeking suggestions, they also want ideas on how best the Agency can share its suggestions with the industry. FDA will receive comments for 60 days after the Notice publlishes into docket FDA-2014-N-0032.
The Notice outlines some common types of deficiencies in CMC, bioequivalence, sterility assurance, Form 356h issues, and DMFs, as well as “fatal flaws” found in the ANDA . FDA is asking that comments and suggestions address one or more of the following types of questions:
1. What aspects of the ANDA application process are confusing or not well defined?
2. What problems do ANDA applicants encounter when developing a submission that FDA could help address?
3. Prior to GDUFA, were ANDA submissions consistently slowed or stalled at certain recurring review points post-filing? If so, why?
4. How should FDA share suggestions for improving ANDA submissions with industry, beyond issuing regulatory guidance?
One of the issues that OGD has yet to address in its review process (and not just since GDUFA, but since the passage of the Hatch-Waxman Act) is the issue of consistency of OGD’s review. While industry’s ANDAs may need to be of better quality, one of the reasons that FDA is having trouble getting quality applications is that, historically, ANDA applicants have tried to make changes to other filings based on past experience in response to the types of deficiencies received from OGD on other applications. However, depending on the reviewer or the specific Division, reviews have historically been quite disparate. Many firms believe they are constantly trying to hit a moving target. While the industry does share some of the blame for the quality in its applications, the Agency also needs to accept some of that responsibility relative to the consistency of its reviews as it is from these reviews that the industry learns what the Agency’s expectations are. There are a number of examples we have seen where similar applications from the same company have received either very different Complete Response Letters (CRLs)/deficiency letters where the issues in the application were essentially the same, or where one ANDA receives a Refuse-to-Receive letter, where another very similar application for a different strength but from the same company (special filing consideration) was received for review.
Please be certain to provide comments to this docket with your suggestions as this is one area that may provide some transparency and insight into issues that are causing problems on both the industry and Agency sides of the review and approval process.