首页 > 资讯 > GPhA激烈批评FDA的仿制药标签提议不切实际

出自识林

2014-02-15 识林

分析点评 — 中文翻译

在反对FDA允许仿制药生产商以CBE-0变更形式作出标签安全性更新的拟议规定的游说的进一步更新中，作为主要的仿制药行业协会，仿制生产商药协会（GPhA）于2014年1月29日发布一份白皮书，抨击该拟议规定，强烈反对该提案，称其“不切实际”并称其会“严重打击”仿制药行业。该白皮书加入了对拟议规定的反对之声中，这些反对的声音中，包括约一周前致FDA Hamburg局长的国会函【FDA仿制药安全性标签变更法律先占性问题引发关注 识林资讯】，也对该拟议规定表示“严重关切”。
在白皮书摘要中，仿制药协会称：
很难高估拟议规定对仿制药行业的意义。该拟议规定以包括不同警告在内的多种不同标签可同时存在于市场上为手段，建立监管架构。在医疗专业人员中造成的混乱，将危害FDA对标签一致性长期和坚定不移的重视。接踵而来的混乱对公众健康有明显的影响，这一点FDA并未在拟议规定中述及。FDA也未开展可靠的成本/获益分析，以最大程度地减小拟议规定如果获得采纳，极有可能导致的保护性标签。FDA也未能认识到，一旦该拟议规定得以采纳，可能导致提高生活质量、降低医疗成本、安全有效的仿制药不被充分采用，上市仿制药减少，生产商从特定市场撤离，药品短缺，以及药品费用增加—这都与1984 年《药品价格竞争与专利期补偿法》（即《食品、药品与化妆品法案（FDCA）Hatch-Waxman修正案>）的基本目标相悖。
我们将持续关注反对FDA提案一事的进展。
北京大学药物信息与工程研究中心 - Garth Boehm博士 2014-02-04
校译：识林-Kapok 2014-02-15

分析点评 — 英文原文

In a further update to lobbying against FDA's proposed rule to allow generic drug makers to make labeling safety updates as CBE-0 changes, the Generic Pharmaceutical Association (GPhA) blasted the proposed rule in a White Paper dated January 29, 2014. GPhA, which is the major generic trade association, came out very strongly against the proposed rule claiming it would be “unworkable” and claiming it would “wreak havoc” on the generic industry. This White Paper joins the chorus of opposition to the proposed rule including the Congressional Letter to Commissioner Hamburg a week or so ago expressing “grave concern” with the proposed rule.
In the White Paper Executive Summary GPhA states:
“It is difficult to overstate the implications of the Proposed Rule on the generic pharmaceutical industry. The Proposed Rule creates the regulatory framework whereby multiple, different labeling, including different warnings, can simultaneously exist in the marketplace for the “same” drug. The confusion that will be created among health care professionals will undermine FDA’s longstanding, unwavering emphasis on consistency in drug labeling. The confusion that will ensue has obvious implications for public health, which FDA has not addressed in its Proposed Rule. FDA also did not conduct a robust cost/benefit analysis, and attempts to minimalize the potential that the Proposed Rule, if adopted, very likely will result in defensive labeling. FDA also failed to recognize that adoption of the Proposed Rule may result in under-adoption of safe and effective generic drugs that improve lives and reduce healthcare costs, fewer generic drugs coming to market, manufacturers withdrawing from certain markets, drug shortages, and increased expense of drugs − all antithetical to the basic purposes of the Drug Price Competition and Patent Term Restoration Act of 1984 (better known as the Hatch-Waxman Amendments to the Food, Drug, and Cosmetic Act (FDCA)).”
We will continue to watch developments in the opposition to FDA's proposal.
北京大学药物信息与工程研究中心 Garth Boehm 博士 2013-12-10

仿制药协会激烈批评FDA的仿制药标签提议不切实际：描绘了一个反乌托邦的未来
2014年2月4日

沃卓斯基兄弟导演的电影<<黑客帝国>>三部曲描绘了一个末世世界，在这个世界中，现实并非看上去那样。多数人认为的“现实”，实际上是机械兽类创造出来的虚拟现实—由于人性“重启”所创造出的梦幻世界。人们没有“真实历史”回忆，也没有远离“真正现实”的记忆。真正的现实是这些机器掌管了世界，制服人类以获取自身的能量。只有少数人打破了这样的虚拟现实，与这些机器对抗。计算机程序员“Neo”选择加入反抗。但是如果要加入反抗，他必须选择吞下红色药片，了解令人痛苦的真正的现实，或者吞下蓝色药片，不知道这些幻象而继续幸福地生活。当然，Neo吃下了红片，故事得以继续。

当我们坐下来，阅读仿制药生产商协会(“GPhA's”)关于FDA2013年11月拟议规定的看法和评价的时候，想起了<<黑客帝国>>三部曲。FDA建议允许仿制药生产商经由待批变更（“CBE-0”）补充申请流程自主更新产品标签（关于产品安全性部分），该流程当前仅允许产品通过NDA批准的品牌药生产商使用。

FDA的提议引起了广泛关注，此情况将持续一段时间。这不仅是2014年GPhA的首要任务，近期几位国会议员也对该提议表示“严重关切”，称其“与法规直接冲突，违背法律的宗旨和目标，并且使制药行业和医疗消费者成本大增”。换言之，FDA的提议是对行业熟知数十年的“真正现实”的背离；另一方面，在一些FDA提议的支持者会表示,是在美国最高法院对PLIVA, Inc. 诉. Mensing, 131 S. Ct. 2567 (2011)案的末日裁决所创造的世界中，这是对仿制药行业的重启。的确，这正如FDA在提议的序言部分所阐述的那样。

1992年，FDA采用通过仿制药法规之时，认为参照药品与其所有仿制药产品标签保持一致是非常重要的，使医师和患者确信仿制药与其参照药品确实等同。然而，随着仿制药行业的成熟，获得了日益增长的市场份额，仿制药与其参照药品标签要求相同的紧张局势不断加重，这样的要求促使仿制药对处方中原研药的替代，同时，ANDA持有者能够独立更新标签，作为其确保标签信息准确且最新的独立责任的一部分。目前的市场状况是，约80%的处方配药为仿制药。FDA认为给予ANDA持有者更新产品标签，以反映通过上市后监测所获得的数据的权力时候到了，尽管这将导致产品间出现暂时性的标签差异。

Mensing判决改变了仿制药生产商的激励机制，该机制使他们遵守现有规定，以开展稳健的上市后监测、评估、报告，同时确保他们的药物标签信息准确和最新。 但是正如很显然选择了“红色药片”的GPhA所言，FDA的提议是不合理和不必要的，将对仿制药行业造成浩劫。

很难高估该拟议规定对仿制药行业的意义。该拟议规定创立了一种监管框架，在该框架下，对于市场上存在的“同一种”药物，可能同时存在多种、不同的标签，包括不同的警告信息。在医疗专业人员中造成的混乱将危害FDA对标签一致性长期的坚定不移。随之而来的混乱对公众健康有明显的影响，这一点FDA并未在拟议规定中涉及。FDA也没有开展可靠的成本/效益分析，以最大程度地减小拟议规定获得通过后，极有可能导致的标签信息过于保守的可能性。FDA也没有意识到，该拟议规定的通过将导致提高生活质量、降低医疗成本的安全有效的仿制药不被充分采用，获得上市的仿制药数目减少，生产商从特定市场中退出，药品短缺和药品费用增加 — 所有这些都与1984年《Hatch-Waxman修正案》的主要目标相悖。

但希望仍存。尽管GPhA明确指出其“不能支持仅仅为了有利于原告律师对仿制药公司的诉讼的、损害公众健康的提议”。GPhA确实认识到了维持最新的安全性标签的重要性 — 但不是在FDA提议所导致的混乱社会中。反之，仿制药协会表示其“支持对流程进行修改，明确允许仿制药公司积极协助FDA，帮助其判断基于新的安全性信息所进行的标签更改是有保证的，并助于对FDA建议变更的有效和及时审查。GPhA完全支持加速沟通流程，通过这一流程，FDA可以将可能的新的安全性信息同时通知仿制药和品牌药公司，还有医疗行业从业人员。” 换言之，GPhA表示，我们应坚持并且提高已经使用了30年的运作系统，没有必要（或理由）进行“重启”。

FDA Law Blog - Kurt R. Karst先生 2014-02-04
校译：识林-Kapok 2014-02-08

GPhA Blasts FDA’s Generic Drug Labeling Proposal as Unworkable; Depicts a Dystopian Future
Posted: 04 Feb 2014 10:48 AM PST
By Kurt R. Karst

The Wachowski Brothers' Matrix Trilogy of movies depict a post-apocalyptic world in which reality is not what it seems. The reality most people perceive is actually a simulated reality created by sentient machines – a dream world created by virtue of a “reboot” of humanity. Those humans have no recollection of “real history” and the break from “true reality.” The true reality is that the machines have taken over the world and have subdued humanity to harvest its energy. Only a few humans have broken free from the simulated reality, and they rebel against the machines. Computer programmer “Neo” is given the option to join the rebellion. But to do so he must make a choice: take a red pill and know the painful truth of reality, or take the blue pill and be blissfully ignorant of the illusion. Of course, Neo takes the red pill and the story moves on.

We were reminded of the Matrix Trilogy when we sat down and read the Generic Pharmaceutical Association's （“GPhA's”） Overview and Assessment of FDA's November 2013 proposed rule. There, FDA proposes to allow generic drug manufacturers to independently update product labeling (with respect to product safety) through the changes being effected (“CBE-0”) supplement process that is currently only available to brand-name drug manufacturers whose products are approved under an NDA.

FDA’s proposal has generated quite a bit of attention, and it will continue to do so. It's not only GPhA's top priority in 2014 (see here), but several lawmakers recently chimed in expressing “grave concerns” with the proposal (see our previous post here), saying that it “conflict[s] directly with the statute, thwart[s] the law's purposes and objectives, and impose[s] significant costs on the drug industry and healthcare consumers.” In other words, FDA’s proposal is a departure from the “true reality” industry has known for decades; a reboot of the generic drug industry in a world created by, what some proponents of the FDA proposal might say is the apocalyptic decision made by the U.S. Supreme Court in PLIVA, Inc. v. Mensing, 131 S. Ct. 2567 (2011). Indeed, FDA says as much in the preamble to the proposed rule:

At the time of FDA's adoption of the generic drug regulations in 1992, FDA believed it was important that product labeling for the RLD and any generic drugs be the same to assure physicians and patients that generic drugs were, indeed, equivalent to their RLD. However, as the generic drug industry has matured and captured an increasing share of the market, tension has grown between the requirement that a generic drug have the same labeling as its RLD, which facilitates substitution of a generic drug for the prescribed product, and the need for an ANDA holder to be able to independently update its labeling as part of its independent responsibility to ensure that the labeling is accurate and up-to-date. In the current marketplace, in which approximately 80 percent of drugs dispensed are generic. FDA believes it is time to provide ANDA holders with the means to update product labeling to reflect data obtained through postmarketing surveillance, even though this will result in temporary labeling differences among products.

The Mensing decision alters the incentives for generic drug manufacturers to comply with current requirements to conduct robust postmarketing surveillance, evaluation, and reporting, and to ensure that the labeling for their drugs is accurate and up-to-date.

But as GPhA, which has clearly chosen the “red pill,” says in its comments, FDA's proposal is unjustified and unwarranted, and would wreak havoc on the generic drug industry:

It is difficult to overstate the implications of the Proposed Rule on the generic pharmaceutical industry. The Proposed Rule creates the regulatory framework whereby multiple, different labeling, including different warnings, can simultaneously exist in the marketplace for the “same” drug. The confusion that will be created among health care professionals will undermine FDA's longstanding, unwavering emphasis on consistency in drug labeling. The confusion that will ensue has obvious implications for public health, which FDA has not addressed in its Proposed Rule. FDA also did not conduct a robust cost/benefit analysis, and attempts to minimalize the potential that the Proposed Rule, if adopted, very likely will result in defensive labeling. FDA also failed to recognize that adoption of the Proposed Rule may result in under-adoption of safe and effective generic drugs that improve lives and reduce healthcare costs, fewer generic drugs coming to market, manufacturers withdrawing from certain markets, drug shortages, and increased expense of drugs − all antithetical to the basic purposes of the [1984 Hatch-waxman Amedments].

But there is some hope. While GPhA says unequivocally that the organization “cannot support a proposed rule that undermines public health merely to facilitate litigation against generic drug companies by the plaintiffs' bar,” GPhA does recognize the importance of maintaining up-to-date safety labeling – just not in the chaotic world that could result from FDA's proposal. Instead, GPhA says that the organization “supports a modification of the process that would explicitly allow generic firms to actively assist FDA in its determination that a change to labeling based on new safety information is warranted and in an efficient and prompt review of proposed changes by FDA. The GPhA fully supports an expedited communication process through which FDA can notify both generic and brand-name drug companies, as well as healthcare practitioners of potential new safety information.” In other words, GPhA says, let's stick with and improve upon the operating system that's been in place now for almost 30 years. There's no need (or justification) for a “reboot.”