首页 > 资讯 > 仿制药生产商能否有效获得其所需参照药品？

出自识林

2014-12-05 Lachman CONSULTANTS

仿制药企业在获取某些保证安全使用措施（ETASU）的风险评估与减轻策略（REMS）参照药品（RLDs）样品以进行必要的生物等效性（BE）研究支持ANDA批准时，一直在经历一个困难时期（至少可以这样说）。今天FDA发布《如何从FDA获得生物等效性研究方案包含可与参照药品适用REMS相若的安全保护措施声明函》。

指南概述了申请人为获得这封函件应采取的步骤，确切的说是为获得含有ETASU的REMS参照药品，否则将妨碍ANDA申请人获得用于BE研究的参照药品（例如，产品可能属于受限流通系统）。一旦将所需信息提交到FDA（通过BE方案，并至少与REMS中概述的患者保护讨论一样好），FDA将审评并决定是需要更多信息，还是申请人的方案符合所有要求。如果方案符合FDA要求，FDA将发函给申请人承认这一事实。此外，他们将发出类似的函件给RLD申请持有人通知他们患者保护可以在提议的BE方案下获得保障。ANDA申请人必须先提供给OGD一份公布信（在指南草案的结尾有公布信模板）允许FDA联系RLD持有人。

FDA称这封信函没有法律要求，但他们（至少这次）没有指出的是，RLD持有人没有义务公布、出售或以其它方式提供BE样品给ANDA申请人，即使FDA将这封信发给他们。据我们了解，美国联邦贸易委员会（FTC）以及国会一些成员正在过问这一问题。

这一故事有两个方面，一是仿制药公司认为RLD持有人的行为是一种贸易限制，因为他们阻碍仿制药公司准备能够最终获批并与RLD竞争的申请。此外，仿制药公司指出美国食品药品管理修正案（FDAAA）中的一节妨碍创新者使用REM的规定，以阻止仿制药竞争（“已获批申请的持有人不得使用任何由卫生部长根据这一小节要求的确保安全使用的要素，阻碍或延迟根据505(b)(2)或(j)的申请，或根据(i)(1)(B)小节—简化新药申请的主题—阻止这类要素的申请。”）创新者认为美国宪法不会迫使他们出售自己的产品给他们选择不出售的人。

所以，你可以经历该过程，FDA可以给你和RLD持有人发信，但是通常情况下，创新者至今都表示他们不愿意销售。这整个问题将很可能由FTC采取行动，国会可能会通过立法，然后最终法院对FTC任何新举措的解释而终结。祝你好运，但不要指望这一问题能很快得到解决。

Lachman CONSULTANTS - Bob Pollock先生 2014-12-04
编译：识林-椒 2014-12-05
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Obtaining Samples for BE Testing for Products with Restricted Distribution Systems or REMS
Written by Bob Pollock • December 04, 2014

The generic industry has been having a hard time (to say the least) in obtaining samples of certain Reference Listed Drugs (RLDs) that have Risk Evaluation and Mitigations Strategies (REMS) with elements to assure safe use (ETASU) upon which to conduct the necessary bioequivalence (BE) studies to support ANDA approval. Today, FDA has published a Draft Guidance entitled, “How to Obtain a Letter from FDA Stating that Bioequivalence Study Protocols Contain Safety Protections Comparable to Applicable REMS for RLD” (here).

The Guidance outlines the steps that an applicant should take to in order to obtain such a letter, specifically, for RLD products with REMS that contain ETASU that otherwise would preclude the ANDA applicant from obtaining those for BE testing (e.g., products that may be under restricted distribution systems). Once the required information is submitted to FDA (via a BE protocol, and discussion of patient protection that is at least as good as that outlined in the REMS), the FDA will review it and make a determination that either more information is necessary or that the applicant's proposal meet all requirements. If the protocol meets FDA requirements, the FDA will send a letter to the applicant acknowledging that fact. In addition, they will send a similar letter to the RLD application holder to inform them that patient protection can be assured under the proposed BE protocol. The ANDA applicant must first provide OGD a release letter (sample copy is included at the end of the Draft Guidance at the link above) which allows the FDA to contact the RLD holder.

FDA states that this letter is on no way a legal requirement, but what they don’t say is that (at least at this point in time), the RLD holder is under no obligation to release, sell or otherwise provide BE samples to the ANDA applicant, even if the FDA sends them this letter. We understand that the Federal Trade Commission (FTC), as well as some members of Congress, is looking into this issue.

There are two sides to this story – one is that generic companies feel the RLD holder's actions are a restraint of trade because they preclude the generic company from being able to prepare an application that can ultimately gain approval and compete with the RLD. In addition, generic companies point to a section of the Food and Drug Administration Amendments Act (FDAAA) that precludes an innovator from using the provisions of a REMS to block generic competition (“No holder of an approved covered application shall use any element to assure safe use required by the Secretary under this subsection to block or delay approval of an application under section 505(b)(2) or (j) or to prevent application of such element under subsection (i)(1)(B) to a drug that is the subject of an abbreviated new drug application.”) The innovators argue that the constitution of the United States precludes forcing them to sell their product to someone they chose not to sell to.

So, you can go through the process, and FDA can send you and the RLD holder a letter, but typically, the innovators so far have indicated they are not willing to make the sale. This entire issue will likely be played out by the actions that FTC may take, legislation the Congress may pass and then ultimately how the courts interpret any new lay of FTC action. Good luck, but don't expect this issue to be resolved any time soon.