2014-05-19 Lachman CONSULTANTS

何时应用FDA指南草案的问题一直比较混乱并且是个有趣的话题。FDA指南（无论是草案或最终形式）应该代表着FDA对于具体问题的当前思考。如果指南草案是新发布的，并且仍在合理的评议期内，那么可能最好的方式是联系FDA看看指南是否可能改变。您往往可以浏览提交到相应卷宗的评议，看看是否有由企业或其它政府机构提出来的具有争议的问题。当已发布指南草案的评议期已过，并且数月甚至数年过去了指南仅仅待在那儿没有定稿时，问题随之而来。

我们的客户经常会问，我是否应该应用指南草案中提出的原则？当FDA发布指南草案时，我是否可以依赖FDA“当前”的思考？好问题，我可以根据经验告诉您，答案大多数时候难以捉摸！通常情况下，当企业根据指南草案的条款做时，FDA的回复是“你不能这样做，因为这仅是指南草案，还没有最终定论。”另一方面，FDA有时给出的缺陷函或完全回复函中指出，你应该应用其某个指南草案中的原则。显然，没有明确的区分“指南”可以让企业做决定。

Lamar Alexander, Orin Hatch, Richard Burr和Johnny Isakson至少4位国会议员在考虑同样的问题。在2014年5月6日发出的一封信函中，4位议员询问FDA关于指南草案的流程和程序以及终结程序。

议员们在信中指出：
今天我们写信表达对于美国食品药品管理局使用指南草案作出实质性政策变化的极大关注。
根据FDA网站“I级指南阐明FDA对于新的重要监管要求的最初解读；描述FDA更早的解读或政策的重大变化；并处理复杂的科学或极具争议性问题。”
相关人士告诉我们指南草案因FDA的政策和立场正日益成为常态。指南草案指出“该指南文件的发布仅用于征询意见。”然而，在没有定稿指南的情况下，草案是FDA审评人员、临床医生和受FDA监管的机构所获得的关于FDA对于重要问题更多当前思考的唯一信息。

国会议员的问题和关注反应了企业在过去几年中表达的许多相同的关注。尤其是对于已经两年还没有定稿的指南草案，人们可能会认为，FDA的思考在卷宗所收到评议的基础上并没有改变。或许应该在明确的时间段之后给FDA一个修订、定稿或撤销指南文件最后期限。这可能强加了一些困难给FDA，众所周知，国会总是喜欢强制立法让FDA开展新举措，但未能给FDA充足的资源以实现新的要求。但是，这种情况下，就考虑FDA指南来说，或许应该合理设置时间期限（比如说评议结束后180天）要求FDA对具体问题得出结论。也许我们应该从1938年联邦食品、药品和化妆品法案中取经，FDA未能在时间框架内定稿的指南文件“被视为”已定稿。FDA指南对于FDA自身和企业而言都是重要的，因为它指示了FDA认为哪些东西需要以何种方式完成以满足FDA的期望。4位国会议员向FDA征求很多有关其流程的信息和文件。让我们希望这次国会质询可以引发一些积极的行动！

Lachman CONSULTANTS - Bob Pollock先生 2014-05-12
编译：识林-椒 2014-05-19

Confused About the Force of FDA Draft Guidance? You Are in Good Company!
Written by Bob Pollock • May 12, 2014

The issue of when to apply FDA Draft Guidance has always been a bit confusing and sometimes an amusing subject. FDA Guidance (whether in draft or final form) is supposed to represent the FDA's current thinking on a specific matter. If the Draft Guidance is newly issued and is still within a reasonable comment period, then it may be best to contact FDA to see if the Guidance is likely to change. Sometimes you can look at the comments submitted to the appropriate Docket to see if there appears to be controversial issues raised by the industry or other government components. The real problem comes when a Draft Guidance is issued and the comment period has passed and months or years go by where the Guidance just sits there in limbo before being finalized.

Our clients often ask, should I apply the tenets in the Draft Guidance? Can I rely on the FDA's "current" thinking when it issued the Draft Guidance? Excellent questions and, I can tell you from experience, the answer is most of the time elusive! Oftentimes, when a firm steps out on the Draft Guidance limb, the response from FDA is “you can't do that because it is only a Draft Guidance and has not yet been finalized.” On the other side of that coin, FDA will sometimes state in a deficiency or complete response letter that you should have applied the principle in one of its Draft Guidance documents. Obviously, there is no clear cut “guidance” for industry to make that decision.

Well, at least four members of Congress, Lamar Alexander, Orin Hatch, Richard Burr and Johnny Isakson, are wondering the same thing. In a letter dated May 6, 2014, the four asked the FDA about their process and procedures for draft guidance and the process for their finalization.

The Congressmen state in the letter:

We write today to express significant concern about the U.S Food and Drug Administration's (FDA) use of draft guidances to make substantive policy changes.

According to the FDA website “Level I guidances set forth the agency's initial interpretations of new significant regulatory requirements; describe substantial changes in FDA's earlier interpretation or policy; and deal with complex scientific or highly controversial issues.”

Stakeholders tell us that draft guidances are increasingly becoming default by FDA policy and position. Draft guidances state that the “guidance document is being distributed for comment purposes only.” However, in the absence of finalized guidance, drafts are the only information that FDA review staff, clinicians, and FDA-regulated entities have on the agency's more current thinking on important issues.

The questions and concerns by the lawmakers reflect many of the same concerns that industry has expressed over the years. One would think, especially for a Draft Guidance that is two years old and has not been finalized, that the FDA thinking has not changed based on comments received to the Docket. Perhaps there should be a deadline imposed on FDA to revise, finalize or withdraw a Guidance document after a specified period of time. This may impose somewhat of a hardship on the FDA-as we all know, Congress likes to impose legislation with new initiatives for the FDA to carry out all the time, but fails to give FDA adequate resources to implement the new requirements. But, in this case ,and, as far as FDA Guidance is concerned, perhaps there should be a requirement for FDA to come to a conclusion on a specific issue in a reasonable set period of time – say 180 days after the comment period closes. Maybe we should take a page from the 1938 Federal Food, Drug and Cosmetic Act and have Guidance Documents that FDA fails to finalize in that time frame become “deemed” to be finalized. FDA Guidance is important for both the Agency and industry, as it instructs what FDA believes is the way in which things need to be done in order to satisfy FDA expectations. The four lawmakers ask FDA for lots of information and documents on its process. Let's hope that this Congressional inquiry leads to some affirmative action!

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