Many of you may be aware of FDA's proposed rule published in November 2013 to allow generic manufacturers to change labelling of their products to reflect new safety information. The proposed mechanism is the same as that used by the NDA holders, submission of a CBE-0 supplement. Ever since Hatch-Waxman came into being, safety related label changes have been made by the NDA holder and then copied by all generics. This served to keep drug labels consistent ensuring that all manufacturers of a given product had the same label.
As a consequence of this procedure, generic manufacturers were not (ultimately) held liable for safety issues not being labeled or not being adequately labeled. This was called “preemption” and in product liability suits by patients claiming injury, generic manufacturers could not be found liable due to labeling deficiencies as they could not change the label. One of the most recent product liability cases that went to the US Supreme Court was decided in favor of the generic manufacturer on the basis of labeling preemption (PLIVA Inc v's Mensing). In this decision the Justices addressed the preemption issue and effectively stated that absent the inability to change the labeling, the manufacturer would have been liable. However they also pointed out that FDA currently has the power to address safety issues in labeling “Congress and the FDA retain the authority to change the law and regulations if they so desire”.
FDA has proposed as it's solution to preemption that generic manufacturers can make safety changes to their label. This would be a huge change to the current situation. Many of these product liability suits result in damage assessments of tens of millions or even hundreds of millions of dollars. Many generic companies cannot afford this liability and are not in a position to make the same kinds of safety assessments that can be made by large brand companies. They already find it difficult, and in some cases impossible to get product liability insurance, and without preemption they would likely find it impossible. The generic industry is very concerned about FDA's proposed change and has objected vigorously to the proposal.
On January 22nd, 28 Congressmen sent a Letter to the Commissioner of the FDA, Margret Hamburg expressing “grave concern” about the proposal. The letter goes on to say “We strongly believe that such a rule would conflict directly with the statute, thwart the law's purposes and objectives, and impose significant costs on the drug industry and healthcare consumers”. The Congressmen then make a number of demands for information from FDA concerning the proposed rule. The information sort is as follows.
1. For the period of time after a generic drug has submitted a CBE-0 supplement, please explain how the generic drug's label will be “the same as the labeling approved for the requirements included in sections 505(j)(2)(A)(i)-(v) of the Hatch-Waxman Act extend beyond the date of approval?
2. Please explain the benefit of having proposed label changes published on a public website before FDA consideration, undermining FDA's current role as the gatekeeper and deciding authority for changes to a drug's label.
3. Please provide the names of any executive branch employees outside the FDA who were involved in the decision to proceed with this proposed rule or who participated in drafting or reviewing it.
4. What is FDA's policy on when an adverse event needs to be listed on the label? Are there standards around the prevalence or severity of the adverse event that are necessary before it rises to a labeling change?
5. What is the expected cost to the FDA to review the CBE-0 submissions in a timely manner and establish and update the website, and from where does the FDA propose drawing resources to meet these costs? How will the agency prioritize submissions and what is the estimated time or review?
6. Please describe in detail how FDA arrived at the estimated cost or the rule of $4,237 to $25,852 per year and estimates it will receive 20 CBE-0 supplements annually from approximately 15 ANDA holders. Please explain how the agency derived these estimates. Did FDA conduct any analysis of how long it takes a manufacturer to prepare a CBE supplement and how much it costs? Did FDA conduct any analysis of what it will cost manufacturers to institute new procedures for monitoring safety and effectiveness of drugs? Did FDA conduct any analysis of the effect the proposed rule will have on drug prices? Please provide all documents and communications regarding the cost-benefit analysis.
7. Generic drug manufacturers can currently propose labeling changes with FDA as a result of newly acquired safety information. Please provide statistics for how many times this is done in comparison to brand name manufacturers and the current causes of any delay when using that process. Please provide any evidence that would indicate generic drug manufacturers are not submitting required adverse event reports or otherwise not meeting their post-market surveillance requirements[.]
8. The proposed rule notes a 2010 study of FDA safety-related drug labeling changes that found the median time from initial approval of the drug product to label change was 11 years. Please provide this study and all supporting documentation to the Committee(s). Please also provide statistics showing how long it takes FDA to make a decision once a label change is suggested.
9. Please explain why the prior approval supplement process alone cannot be used effectively to change generic and brand drug labels, and the current causes of any delay when using that process. Please provide any evidence that would indicate generic drug manufacturers are not updating their label upon FDA approval of a change to the label of the reference brand drug.
10. As an alternative approach, did the FDA consider permitting generic drug manufacturers to use a modified CBE process by which the agency has an opportunity to assess a proposed labeling change before introducing it into the market? What does the agency believe would be the pros and cons of using this approach as opposed to the CBE-0? Did the agency conduct a cost benefit analysis of such an approach?
11. Did the agency consider the impact the proposed rule would have on over-the-counter (OTC) drugs? If so, please submit any such analysis and explain how FDA envisions the proposed regulation applying to OTC drugs.
FDA has until February 5, 2014 to respond to the letter.
This is potentially a very serious economic issue for the US generic industry. The fact that litigation can be pursued on a contingency basis, where a lawyer or law firm agrees to take on the case for a portion of the eventual damages (often 30% or more) mean that anyone can bring such a product liability case. Juries tend to be sympathetic to the injured plaintiff and many times find in favor of the plaintiff and award huge damages. Although companies that manufacture drug products do not prescribe them, they are sued based on a “defective product” theory because they have more money than other people directly involved in the prescribing.
We can only hope that this proposed change does not go into effect, or if it does that it is stuck down by the courts as against the current law. If neither of these things happens, then Congress will have to step in or the existence generic industry as we know it will be seriously threatened.
，向她表达了对于此提案的严重关切。信中写道“我们坚信，这样的规定将会直接与法规冲突，有悖于法律的宗旨和目标，并且使制药行业和医疗消费者成本大增”。这些国会议员对FDA就该拟议规定的信息提出了一些要求。这些信息分类如下。