The new FDA reality




The spirit at the last FDA town hall meeting at TCT 2013 in San Francisco was somewhat different from previous town halls with FDA academia and industry. The tone of the meeting was that of change and transformation in the regulatory culture of cardiology devices. For decades the notion was that the regulatory approval process of medical devices in the US was cumbersome, lingering, ineffective, and expensive. This resulted in frustrated sponsors, the migration of off shore investigation of new devices, delayed access of new technology in the US, and frustrated patients and physicians forced to seek out new devices outside of the US. Over the past three years, apparent efforts have been made by FDA leadership and reviewers to innovate and reform the process by attempting to improve the efficiency and timing for approval of medical devices. This then led to an atmospheric change to foster excitement that new things are happening, or are about to happen, within the FDA. This excitement immediately raised expectations and questions from academia and industry: Is the regulatory process really undergoing transformation that will result in a more efficient process with expedited timelines? Or are we simply experiencing a ‘new’ FDA?


What led to this notion were several initiatives and enhanced communications undertaken by Agency leadership and reviewers within the last two years. The most recent initiative posted on the FDA website , CDRH 2013 Strategic Priorities, details a new set of priorities and reorganization for the Center. Included are innovative regulatory processes that should impact the overall regulatory approval process for medical devices. In addition, there is the Early Feasibility Study (EFS) program and a new FDA program to revitalize early clinical research in the US.


In an editorial published in this Journal in 2011 we called for a program revival that would facilitate first-in-human trials for new technology in the US . The FDA responded with the EFS program that facilitates the clinical evaluation of medical devices in the US under the Investigational Device Exemptions (IDE) regulations and published a guidance document on this initiative in 2013. The new EFS program includes new approaches to facilitate timely device and clinical protocol modifications during an early feasibility study. As a result, a change in the direction of early feasibility studies occurred and after of decade with nearly no feasibility studies in the US, several sponsors committed to conducting their EFS studies here.


In addition, the FDA drafted guidance with respect to IDE decisions and in July 2012 the Food and Drug Administration Safety Innovation Act (FDASIA) became a law. This law gave the FDA a new and powerful expedited drug development tool, known as the “breakthrough therapy” designation. This new designation helps the FDA assist drug developers to expedite the development and review of new drugs with preliminary clinical evidence, indicating that the drug may offer substantial improvement over available therapies for patients with serious or life-threatening diseases. The FDASIA also sought to further medical device innovation, although actions related to medical devices specifically directed at implementing the FDASIA were not included in CDRH 2013 Strategic Priorities.


The FDASIA explicitly mandates that IDEs cannot be denied unless there are patient safety issues per the FDA. The FDA cannot disapprove an IDE on the sole basis that the FDA believes that effectiveness end points may be unacceptable to seek for a post market application (PMA) approval. Why hasn’t this change brought about more IDEs and device development within the US? A possible answer could be that the final bar for PMA approval is still a reasonable safety and effectiveness benefit. Another explanation could be that the bar for safety is too high and the requirements to demonstrate safety may have increased and are not well characterized for these IDE trials. Thus, a sponsor may feel that although the FDASIA law may make it easier to be granted approval to start, it may not be easier to get a device approved.


The FDA has now proposed the streamlining of clinical trials. To achieve this, they have projected the development of framework around appropriate, timely and efficient IDE decisions tailored to the type of study with a focus on the framework of benefit-risk decision making. This decision-making pathway will consider the right balance between pre- and post-market studies. The balance will look specifically into the following questions:




  • Can a decision on safety and effectiveness be reached with potentially fewer data or shorter follow-up durations with a prospective plan to collect data in the post-market setting?



  • For mature technology with significant real-world experience, can the pre-market data requirements be altered?



Post-market device registries are now considered to be an important source of clinical safety and effectiveness information and have led to labeling changes. The proliferation of the electronic medical record (EMR) has given rise to a more efficient and real-time data collection process of real-world usages of medical products that may change the ratio of pre-/post-market data requirements from the Agency, potentially leading to earlier market release.


Perhaps the notion of a ‘new’ FDA was derived from the improved communications between industry and the Agency via pre-IDE and concept meetings, and from enhanced involvement with academia via conferences, symposia, and face-to-face interactions at meetings such as TCT and CRT. These improved communications have led to better work-flow processes, and greater trust and understanding of the laws and regulatory pathways.


Although the FDA’s efforts are positive and are headed in the right direction, they are only evolutionary, and put in doubt whether these improvements will result in a significant change to the timing and efficiency of the medical device regulatory processes. The key component to any change in this process should be within the core principle of benefit/risk ratios. This principle is imbedded in the IDE application, and allows FDA regulators to consider the totality of the benefit/risk profile for the device throughout the entire evaluation process. This principle is the critical path for approval. Given the current length to receive PMA approval for most devices, should an alteration to this final and total review of the benefit/risk assessment be performed at varying time points throughout the investigation? This would lead to some medical devices being released for market approval with different benefit/risk ratios, as long as the medical communities and patients are fully informed of these varying degrees of benefit to risk.


In clinical practice we operate based on different levels of evidence, comprised of recommendations and guidelines from committees and professional societies. This way, physicians and patients are informed and can choose appropriate treatment strategies based on the benefit/risk ratio and the level of evidence. What the regulatory agency needs is the freedom to have different levels of approvals based on the benefit/risk ratio, and must be able to grant conditioned approval while other data, including post-marketing data, are collected. In order to get the full assurance of the benefit/risk ratio, sponsors will be required to complete the full testing and evaluation; however, with this proposed approach they could complete this while marketing the product. Similar to the guidelines, there should be designated low-, intermediate-, and high-risk/benefit ratios so physicians and patients can take them into consideration when selecting a device or treatment strategy.


In Europe and Canada, although not the gold standard, and not as robust in regulatory sciences, medical device innovation and manufacturing, when it comes to the approval process, the acceptable benefit/risk ratio is different and often unknown due to lack of sufficient testing and clinical data. Yet this does not prohibit those agencies from shortening the approval cycle; and those patients have access to new technology and new medical devices years before US patients. The question is how many lives can be saved or quality of life improved versus how many will be put at risk if the US adopts a lower benefit/risk ratio for initial PMA approval?


In order to consider such an approach in the US, the law must be changed. Many aspects regarding the efficiency and timing related to device approval now depend on changing the law. Therefore, when asking the question, Is there a ‘new’ FDA with regard to approval for marketing of medical devices? The answer is, not so fast! While the recent steps and priorities from the Agency are welcomed, these by alone are not sufficient to achieve the desired change, which is real transformation in the regulatory process. It is now the role of the government to step in and change the law to enhance the regulatory process. So instead of targeting the FDA and holding it responsible for delays in the approval process within the US, we should focus our efforts on Congress and the Senate to lobby for a change in the law that would enable the Agency to act more efficiently to approve medical devices for market. This should lead to what we all desire: a ‘new’ FDA.


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Nov 14, 2017 | Posted by in CARDIOLOGY | Comments Off on The new FDA reality

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