2014-03-24 Lachman CONSULTANTS

仿制药生产商协会就标签拟议规定向FDA提交评论

3月13日，仿制药生产商协会公布了一份24页的意见，回应FDA允许仿制药申请人在FDA批准前或在所引用橙皮书收录的参照药品标签信息的修订之前，单方面添加或修改标签中警告的拟议规定。

评论一经公布，就可以在regulations.gov网站上获取全部内容。对该拟议规定的意见主要包括：

(1) 拟议规定超出FDA的职权，并与食品药品与化妆品法案（FDCA）中明文规定的多项条款相悖；

(2) 将给医务工作者以及消费者带来不必要的困惑，因而将患者置于风险之中；

(3) 既没有任何ANDA申请人历史上无法履行其监管义务的经验证据支持；也没有ANDA申请人履行这些义务的动因由于美国最高法院的近期判决发生改变的经验证据支持；

(4) 基于一个有缺陷的前提-ANDA申请人日常接收与获取可能构成新获得的安全信息数据，使得他们有必要对产品标签信息提出与安全性有关的变更；

(5) 有可能破坏消费者与医保提供商对仿制药与其对应品牌药等同的信心；

(6) 将使得仿制药行业暴露于大量和不必要的各州法律侵权诉讼以及可能的侵权责任之中；

(7) 将会极大地增加仿制药行业的负担，并因此不必要地推高仿制药成本，对患者没有增量获益。

此外，仿制药生产商协会称：对于修改现行规定的必要性，FDA没有提供任何客观证据。

不同评论者对该拟议规定的评论，大致反映了在标签一致性方面FDA三十多年来一直坚持、却在其最近的文件中背道而驰的法律与监管立场 -仿制药必须与参照药品保持相同的标签信息，避免在市场上引发混乱，并向医师、患者以及医保提供商保证仿制药安全性与有效性与相对应的品牌药相同，因此是可以完全的。一旦采用目前书面的规定，势必将抛弃这些理念，并将仿制药生产商、患者、药房以及医保提供商轻而易举的导入歧路。此外，上述问题一旦通过，即使只考虑短时间内所包含的不同安全性信息，也将给仿制药相互之间是否一致带来疑问。

仿制药生产商协会指出，FDA漏洞百出地推理最高法院对Mensing诉状裁决以某种方式削弱了ANDA持有人采取适宜的药物警戒措施的动因，然而FDA并未提供任何实际发生的经验证据。仿制药生产商协会还恰如其分地指出，如果FDA认为仿制药申请人未能达到安全性报告的严格监管要求，其实有强制手段应对这些拖延履行义务的申请人，而不应无端设立新规定，在这样的纠正会令整个行业陷入混乱的情况下，去纠正之前并不存在的问题。

此外，仿制药生产商协会义正辞严地表示，很明显仿制药申请人并不具有安全性数据库，只是收到有关自身产品、而不包含其他生产商相同产品的一小部分不良反应信息，并不处在判断孤立事件重要性的位置上。另一方面，FDA可以看到来自所有生产商的信息，也可获取来自原研药申请人的全部安全性数据，因此处于作出精确和相应分析并对潜在安全信息作出评价的更好位置上。因此，在该评论中所罗列的种种原因下，评论者得出结论认为，“简言之，这一拟议规定强加了既不合理又无必要的负担—将增加企业发布警告的责任，无法妥善证实，还有可能与《食品、药品与化妆品法案》有关错标的要求相悖。”

那么FDA正在做什么？向法院提供一种使用合理运用监管职权的途径？许多人同我一样，并不这样认为。仿制药生产商协会得出的结论是：“拟议规定只是FDA试图提供给大家一种提起诉讼的手段，这样的事情不应为FDA所关注”。这背离了FDA理应关注的推进Hatch-Waxman法案的目标，确保消费者以可以实惠的价格获得安全有效的药品。患者与医师理应获得一致、透明的信息渠道，使得知情治疗决定万无一失。FDA现在草拟的规定将严重损害这些目标。”请找出并浏览仿制药生产商协会的所有评论，告诉你们的议员（以及所有意了解者），敦促他们维护Hatch-Waxman法案过去三十余年在降低医疗保健成本以及向患者提供可靠的仿制药来源取得的成果。请记住这一监管过失的代价将由大家共同负担！

Lachman CONSULTANTS - Bob Pollock先生 2014-03-14
校译：识林-Kapok 2014-03-22

GPhA Submits Comments to FDA on Proposed Rule
Written by Bob Pollock • March 14, 2014

Yesterday, the Generic Pharmaceutical Association (GPhA) provided 24 pages of comments in response to the FDA's Proposed Rule to permit generic applicants to unilaterally add or modify warnings in its label prior to FDA approval and prior to the revision of the reference listed drug's (RLD) labeling.

The entire set of comments can be found here, once the comments are posted on regulations.gov. The key messages of the comments are that this Proposed Rule:

(1) Exceeds FDA's authority and are contrary to the express provisions of the Food, Drug, and Cosmetic Act (FDCA);

(2) Would lead to unwarranted confusion for healthcare providers and consumers, and as a result, put patients at risk;

(3) Is not supported by any empirical evidence that ANDA applicants have not complied with their regulatory obligations historically or that the incentives for them to comply with those obligations have been altered in light of recent United States Supreme Court decisions;

(4) Is based on a flawed premise that ANDA applicants routinely receive or possess data that may constitute newly acquired safety information alerting them to a need to propose safety-related changes to product labeling;

(5) Threatens to undermine the confidence consumers and healthcare providers have in generic drugs because they are the same as their brand-name counterparts;

(6)Would open the generic drug industry to massive and unwarranted state-law tort litigation and possible liability; and

(7) Would greatly increase the burdens on the generic drug industry and, therefore, would unnecessarily increase the costs of generic pharmaceutical products without an incremental benefit to patients.

Moreover, GPhA says, FDA has not provided any objective evidence of a need to change existing regulations.

The comments echoed by many of the commenters to the Proposed Rule outline the statutory and regulatory position the Agency has held for over 30 years regarding the label “sameness” requirement and cites recent documents in which the FDA has stood firmly behind the notion that the generic product must bear the same labeling as the RLD to prevent confusion in the marketplace and to provide assurance to healthcare practitioners, patients and care givers that the generic product is as safe and effective as its brand name counterparts and are, therefore, fully substitutable. Adopting the Rule as currently written will throw those concepts out the window and put generic manufacturers, patients, pharmacies and healthcare providers up the proverbial tributary without any physical means of propulsion. In addition, it will leave in doubt whether any generic product is the same as another if all are permitted – even for a short period of time-to contain different safety information.

GPhA points out FDA's flawed reasoning that the Mensing Supreme Court decision somehow lessened ANDA holders' incentive to conduct appropriate pharmacovigilance activities, but without any empirical evidence that this has actually occurred provided by the Agency. GPhA also aptly notes that if the FDA believes that generic applicants are failing to meet the strict regulatory requirements for safety reporting, then they have enforcement tools to deal with those applicants that lag on their responsibilities, and not use new and unwarranted regulations to fix a problem that does not exist where such a fix would send the industry into chaos.

In addition, GPhA rightfully states the obvious that generic applicants do not have the safety database and receive only a small portion of the adverse event information and only for their product and not the for the same product of other manufacturers, so they are not in a position to judge the significance of isolated events. The FDA, on the other hand, does see information from all manufacturers, and also has access to the entire safety database in the innovator's application, and thus, is in a far better position to make accurate and relevant analysis and evaluation of potential safety information. For these, among other reasons articulated in the GPhA's comments, the comments conclude, “in short, the proposed rule imposes an undue and irrational burden—it would create an obligation to provide warnings that cannot be properly substantiated and that may run afoul of the misbranding requirements of the FDCA.”

So what is FDA doing here? Is providing access to the courts an appropriate use of its regulatory authority? I think not, and many join in my view. GPhA says in its conclusions that '[T]he proposed rule is an attempt by FDA to provide people with a means to file lawsuits, a matter that should be of no concern to FDA. It strays from what should be a matter of concern to FDA furthering Hatch-Waxman's goals of making safe and effective drugs available to consumers at affordable prices. Patients and healthcare practitioners must continue to have access to consistent, transparent information in order to best inform treatment decisions. The FDA's rule as presently drafted would severely undermine those goals.” Please seek out and read the full comments of GPhA and then speak to your Congressmen (and anyone else that will listen) and urge them to keep the 30 years of success of Hatch-Waxman in lowering associated healthcare costs and providing unfettered access of generic drugs to patient from being something of the past. Remember the cost of this regulatory misstep will be borne by all of us!