首页 > 资讯 > FDA的标签修改拟议规定仅影响标签印刷开销？

出自识林

2014-02-15 Lachman CONSULTANTS

如果你认为FDA的标签修改拟议规定仅影响印刷标签的开销——请三思！

智囊机构美国企业研究所（AEI）的Alex BrillBrill也不这样认为，并在为美国仿制药生产商协会（GPhA）开展的一项经济学分析中表达了自己的观点。该项研究概括了FDA在评价中显然忽视相关下游成本的下列领域：

• 仿制药生产商将面临更高的保险费、自身担保成本以及用于承担产品责任的储备金。
• 当感受到更大的责任风险或者不承保的责任风险后，仿制药生产商将退出或不再进入特定药品市场。
• 当面临增加风险作承保导致仿制药生产商保费增加时，为仿制药生产商提供产品责任险的保险公司可能退出该市场。
• 仿制药生产商需承担所仿制药品的品牌药公司监控与安全性问题有关的不良事件报告工作的成本。

这项研究得出结论认为，FDA拟议规定将导致对消费者与政府显著增加大约40亿美元/年之巨的仿制药开支，其中政府被套牢的金额约为15亿美元，私人健康保险约为25亿美元。Brill博士还指出，拟议规定将抬高仿制药生产商的责任险开支，并极有可能导致对过度警告的鼓励，这将冲淡重要警告、不良反应以及禁忌症的重要性。正如FDA自己在2006年联邦公报通告《人用处方药与生物制品标签的内容与格式要求》中所声称的：

“FDA注意到，对责任的关注将给生产商带来压力，扩展标签警告，将推测性的风险纳入，因此，限制了医生觉察到潜在的更为严重的禁忌症与副作用……过度警告，与欠缺警告一样，对患者安全与公众健康有着同样负面的作用。”

由于FDA已有做出标签变更的流程（即使对仿制药申请者而言），Brill博士与其他业界人士一样，似乎看穿了FDA掩饰了将标签变更规定提案掩饰为一个安全性议题的企图，而与此同时，正如执行《Hatch-Waxman法案》规定的现行监管框架所概括的更为合理的方法那样，FDA已经有标签变更流程就位（甚至是针对仿制药的）。谈及FDA对拟议规定拟议规定的经济学分析，Brill报告表达了如下的观点：“我们断定FDA关于拟议规定的假设不完整也不准确，使得他们的经济学分析毫无意义”。该研究还称：“FDA并未在其估算中考虑到责任成本，只是简单地拒绝考虑这一问题。”

此外，已有至少两家本博主联系的企业，估计由于FDA强制或由原创公司批准变更标签，每家会损失约150万美元。现在，请考虑仿制药生产商每次在收到一份不良事件报告后即开始变更其标签的成本，以及为试图减少其违责风险的防御性变更标签所导致的标签变更所造成的级联效应。

在解释上述观点时，该报告还指出：“FDA预期所有企业将出于自身利益运作是正确的”。然而，FDA从根本上误读了攸关利益。药品生产商将受其法律义务的驱使，希望最大程度地降低产品责任诉讼所引起的诉讼风险。潜在的“未能警告”诉讼将强烈鼓励每一个仿制药生产商争先提交一份CBE-0补充申请。因此，FDA对“除近期新药申请持有者所递交的之外将不会有CBE-0补充申请”的假设是难以置信的，相较于FDA所估计的“20份CBE-0补充申请将自新药申请持有者转向简化新药申请持有者的变化”，我们也可以预料到更大的影响。”

该研究也指出，一旦这项规定得以敲定，仿制药的责任险保费将增加；每个人都需要清楚的是，在该研究中提及的所有开支增加，最终将由消费者买单。在这个成本约束而政府开支问题蔓延的时代，当然也没有增大医保预算的机会。我们需要务实并清楚该拟议规定的来龙去脉。到了应当后退一步寻求实际问题的实际解决方案的时候了，而非FDA不该尝试去解决的问题的实际解决方案。

Lachman CONSULTANTS - Bob Pollock先生 2014-02-05
校译：识林-Kapok 2014-02-15

So You Think the FDA's Proposed Label Change Rule Will Only Impact the Cost of the Printed Labeling – Think Again!
Written by Bob Pollock • February 05, 2014

Alex Brill doesn't think so either and in phttp://www.gphaonline.org/gpha-media/press/generic-pharmaceutical-association-gpha-urges-administration-to-consider-patient-risk-implications-of-proposed-rule-on-labeling an economic analysis] conducted for GPhA, he makes his point. The study outlines the following areas that FDA's assessment apparently overlooked relative to downstream costs:

• Generic manufacturers would face higher insurance premiums, self-insurance costs, and reserve spending on product liability.
• Generic manufacturers may exit or decline to enter the market for certain products for which they perceive greater liability risk or uninsurable liability risks.
• Insurance companies offering product liability insurance to generic manufacturers may leave the market when faced with insuring against increased risk, resulting in higher premiums for generic manufacturers.
• Generic manufacturers would bear the cost of duplicating brand companies' efforts to monitor adverse events reports for safety-related issues.

The study concludes that the FDA Proposed Rule will result in significantly higher generic drug costs to the consumer and the government to the tune of $4 billion/year, with the government on the hook for about $ 1.5 billion and private health insurers about $2.5 billion. Dr. Brill also acknowledges that the Proposed Rule will raise the cost of liability insurance for generic companies and is likely to also result in an incentive to overwarn, which would dilute the importance of major warnings, adverse events and contraindications. As stated by the FDA in its own 2006 Federal Register Notice on “Requirements on Content and Format of Labeling for Human Prescription Drug and Biological Products”:

“FDA noted that liability concerns were creating pressure on manufacturers to expand labeling warnings to include speculative risks and, thus, to limit physician appreciation of potentially far more significant contraindications and side effects. . . . Overwarning, just like underwarning, can similarly have a negative effect on patient safety and public health.”

Dr. Brill, like many others in the industry, appears to be able to see through the Agency’s veiled attempt to make the Label Change Proposed Rule a real safety issue, as the FDA already has a process in place to make label changes (even for generic applicants), but in a more reasoned approach that is outlined in the current regulatory framework of the implementing regulations to the Hatch-Waxman Act. And when discussing FDA’s economic analysis of the Proposed Rule, the Brill report states the following: “We assert that the FDA’s assumptions about the Proposed Rule are incomplete and inaccurate, rendering their economic analysis moot.” The study goes on to say, FDA fails to consider liability costs in its estimates and simply dismisses this issue.”

In addition, at least two firms contacted by this blogger provided estimate of about $1.5 million each that they lose in costs today, based on labeling changes that are either mandated by FDA or approved for by the innovator. Now, consider the cost of label changes alone if generic manufacturers began changing their labels each time they received a report of an adverse event, and the cascade of label changes that would be the result of defensive label changes in an attempt to lower their liability exposure.

In explaining the above point, the report states: “The FDA is correct in assuming that every firm can be expected to operate in its own interest. However, the agency fundamentally misrepresents the interests at stake. Drug manufacturers will be driven by their legal obligations and desire to minimize the risk of litigation arising from product liability suits. Potential failure- to-warn suits would provide a strong incentive for every generic manufacturer to be the first to submit a CBE-0 supplement. Therefore, the FDA’s assumption that “there will be no CBE-0 supplements in addition to the current level submitted by NDA holders” is implausible, and we should anticipate a far greater impact than the agency's estimate of a shift of 20 CBE-0 supplements from NDA holders to ANDA holders.”

The study also points out that, should this rule become final, generic liability insurance premiums will increase; it should be clear to everyone that all of these increased costs described in the study will be borne by the ultimate consumer. Certainly, in this time of cost constraint and rampant government spending, this is no time to open the health care piggybank. Let's be realistic and clear about the “what” and the “why” of this Proposed Rule. Time to take a step back and get to the real solution to the real problem, not the problem that FDA should not be trying to solve.

原文请见 So You Think the FDA’s Proposed Label Change Rule Will Only Impact the Cost of the Printed Labeling – Think Again!