首页 > 资讯 > FDA具体产品生物等效性指南修订后的思考

出自识林

2016-10-05

10月4日美国FDA发布67份具体产品生物等效性（BE）指南，其中34份新增33份修订，这是今年第三次批量发布和更新BE指南。FDA一直忙于放出新的BE指南和修订过去的指南文件。根据GDUFA II的新规定，仿制药办公室（OGD）将设定目标在最早合法批准日期至少两年之前针对90%的产品发布具体产品BE指南。【GDUFA II期关键条款一瞥（二） - 识林资讯 2016/9/24】

虽然这一举措对于产品研发人员来说是好消息，但也可能破坏公司计划，尤其是当BE指南被修订时。下面是剧情简介：

OGD通常从申请人那里以ANDA提交、BE检测方案、受控函甚至通过来自原研商请愿的形式接收信息学习并形成意见。随着FDA学习了所接收的信息，发布具体产品BE指南草案。很多时候在指南发布后，原研商将会打岔进来发表意见，或者一旦提交了使用现有指南的BE研究，FDA对数据的审评可能表明研究并不能充分支持BE结果。在以上任一情况下，如果原研商的科学论据是有说服力的，或者FDA意识到原来的指南是不充分的，FDA可能会稍微修改指南，或在某些情况下根据审评意见建议大幅修订。

试想一个申办人正准备提交ANDA，却发现开展的研究不再是指南建议的。未决ANDA会怎样呢？企业将需要根据FDA修订的BE指南提交新的研究吗？那么那些产品已经根据先前BE指南获批而FDA在批准后修订了BE指南的企业呢？企业需要使用新BE指南执行研究吗？如果是这样，在新研究尚未完成和审评期间FDA指定的治疗等效性评估又会发生什么变化？

所有这些都是合情合理的问题，这要求企业对BE指南建议的变化保持密切关注。如果FDA能清楚地说明对BE指南所作的修订，无论是通过在文件中用红线标出变化，还是通过与修改后的文件一同提供变更历史，可以帮助企业评估内容方面的修订。因为一旦发布修订指南，之前的版本便不再能从FDA网站获得，这使得评估具体变化变得十分困难。从这一点上讲，识林可以帮助企业完成对BE指南历史版本的归档，但上述提到的具体问题仍需要企业认真考虑并与FDA良好沟通。

Lachman CONSULTANTS - Bob Pollock先生
整理：识林-椒
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FDA Releases 34 New and 33 Updated Bioequivalence Guidance Documents
By Bob Pollock | October 4, 2016 原文地址

FDA has been busy putting out new bioequivalence (BE) guidance documents and revising others. Under the new provisions of GDUFA II, the Office of Generic Drugs (OGD) will set a goal of issuing 90 product-specific BE Guidances at least 2 years prior to the earliest lawful approval date (here) of an innovator product.

While this activity is good news for product developers, it can throw a real monkey wrench into the firms' plans, especially when BE guidance is revised. Here is the story line. OGD often learns and forms opinions from the information it receives from applicants in the form of ANDA submissions, protocols for BE testing, controlled correspondence, and yes, even through petitions from innovators. As the FDA learns from the information it receives, it issues product-specific draft BE guidance. Many times after the guidance is issued, the innovator will chime in, or once BE studies are submitted using the existing guidance, the FDA review of the data may suggest that the studies are not sufficiently supportive of a BE finding. In either case, if the innovator is persuasive in their scientific argument or the FDA recognizes that its original guidance is not sufficient, FDA may revise the guidance slightly or, in some cases, recommend a major revision to its recommendations based on its review.

Imagine a sponsor getting ready to submit its ANDA only to learn that the study it conducted is no longer recommended. How about pending ANDAs? Will the firm need to submit a new study based on the FDA's revised BE recommendation? What about firms that have approved products that were based on a previous FDA recommended BE design that the Agency revises post-approval? Will the firm need to perform a study using the new recommendation? If so, what happens to the FDA’s assigned therapeutic equivalence evaluation during the pendency of completion and review of the new study?

All of these are legitimate questions and require firms to stay on top of changes in recommendations made to BE guidance documents. One thing that might help firms assess the revisions in that regard, is if the FDA would clearly articulate what revisions it makes to a BE recommendation either by redlining the changes in the document or by providing a change history to accompany the changed document. Why? Because once a revised guidance is issued, the previous version can no longer be accessed making evaluating the specific changes very difficult. Just a suggestion, FDA (if you are reading this blog)!