December 11, 2018
By: Scott Gottlieb, M.D.
FDA Commissioner Scott Gottlieb, MD
Advanced technologies, biomaterials and digital tools are offering us fundamentally better ways to develop new medical devices to advance human health. To build on these innovations and ensure patients have access to safe and effective advances in medical care, it’s crucial that FDA modernize its policy framework for the review of medical devices. We must provide more opportunity to enhance traditional products with new advances, and to use these same innovations to develop fundamentally novel devices altogether. This requires FDA to implement reforms that make the review process more benefit-risk based; allow us to efficiently adopt more modern tools for evaluating safety and benefits of new products; and to actively embed in our review patient-centric measures of risk and benefit.
We must do this all while taking steps to strengthen FDA’s gold standard for safety and effectiveness.
FDA already has taken steps to modernize its review pathways in recent years as device technologies have advanced. But there’s more we must do. Early in the coming year, FDA’s Center for Devices and Radiological Health (CDRH) intends to advance several important new regulatory policy initiatives to further modernize the medical devices program and continue to foster new medtech innovation.
Background on the Current Framework
The Medical Device Amendments of 1976 set forth that manufacturers of new, moderate-risk devices – generally Class II and certain Class I devices – must demonstrate substantial equivalence to a similar device legally marketed in the U.S. in order for a new device to be cleared by FDA for use in patient care. Under this construct, older devices that function as the comparators are referred to as predicate devices. This process is generally known as the 510(k) pathway. It’s designed to assess the safety and effectiveness of medical devices whose risks are well understood.
FDA’s regulatory process has remained largely unchanged since it was first implemented 40 years ago. As a consequence, there are an increasing number of cases where this basic framework isn’t well-suited to reflect the innovation that we see today in certain technologies, and how we must evaluate those technologies..
FDA’s existing framework also fails to realize the full potential of the FDA’s consensus standards program, which was established through the Food and Drug Administration Modernization Act of 1997, and will be refined and expanded as a result of provisions in the 21st Century Cures Act of 2016.
Through this program, CDRH has already recognized more than 1,200 national and international standards wholly or in part. CDRH typically incorporates these standards in guidance documents that provide recommendations on testing and performance standards. These guidance documents provide innovators with predictable, consistent, and least burdensome approaches for demonstrating that a new technology is safe, effective, and functions properly for its intended use.
Yet despite manufacturers being able to demonstrate that they meet these consensus standards, a manufacturer is required to demonstrate that a device is substantially equivalent to an existing, legally marketed device. But the predicate devices that new products must compare themselves to are sometimes 40 years old. FDA recognizes that such direct comparison testing creates burdens for 510(k) applicants, especially when many new devices are designed in novel ways, using more advanced technologies. It’s sometimes hard to identify sufficient, appropriate predicate devices in order to conduct testing. This can create an obstacle to certain kinds of innovation and lead to inefficiency in the review process with few, if any, benefits to patient safety. In fact, at times, it can make it less efficient for FDA to assure the safety of the device.
New Steps to Reform, Modernize 510(k) Review
To address these challenges, in the first quarter of 2018, FDA intends to publish a draft guidance outlining a voluntary, alternative pathway for demonstrating substantial equivalence. This pathway will allow more flexibility to use more modern criteria as the reference standard, and permit comparisons to standards that more closely approximate the kind of novel technology we’re being asked to evaluate.
Under this new framework, device manufacturers could demonstrate substantial equivalence by meeting objective safety and performance criteria. These can include FDA-recognized standards, FDA-developed guidance documents, or a combination of the two, which embody the safety and performance criteria that new devices could meet to be cleared under a 510(k). This pathway would be available for pre-specified categories of mature devices – those for which safety and performance criteria that meet or exceed the performance of existing, legally-marketed devices can be identified. It will be outlined in new draft guidance that we are announcing today in the Federal Register and plan to issue in the first quarter of 2018. This approach will also make it easier for FDA to conform its framework for evaluating new products to international consensus standards where such standards exist.
The program will be voluntary, and manufacturers could continue to utilize the existing 510(k) pathways. It would apply only to devices for which 510(k) clearance is the appropriate pathway to market and would not affect the scope of the current De Novo program for more novel devices that do not have a predicate. But imagine the benefits of a more efficient and transparent pathway for bringing to market well-understood technologies like ultrasound imaging machines, common in vitro diagnostic devices, and blood pressure monitors.
This regulatory innovation holds tremendous promise to further streamline device review for sponsors and FDA and allow new innovations to get to patients more quickly; to allow more advanced technologies to be efficiently incorporated into new devices; and to foster greater confidence in the FDA’s ability to efficiently evaluate safety and benefits of technologies cleared under this pathway – all while maintaining the same gold standard that we apply to existing review processes. By modernizing the benchmarks by which we evaluate the performance characteristics of cleared devices, we believe it will also enable us to put in place more modern criteria for assessing safety.
New Framework to Balance Pre- vs. Post-Market Requirements
For all medical devices that are subject to premarket review – whether through a premarket notification, premarket approval application (PMA), humanitarian device exemption application (HDE), or other type of marketing submission – FDA must determine whether probable benefits to health from use of the device outweigh any probable risk of injury or illness from its use. As part of that analysis, FDA considers what level of uncertainty is acceptable about the product’s probable benefits and risks before the device is available to the public. To fully discharge any uncertainty, FDA requires post-market follow-up studies. These studies are a way to fully elucidate the long-term performance of new medical products.
But the balance between acceptable uncertainty in the pre-market setting, relative to a product’s benefits and potential risks – and, in turn, how much reliance FDA can place on post-market follow-up studies – has never been objectively defined in one, comprehensive policy framework.
FDA intends to publish a draft guidance, again in early 2018, setting forth factors that the agency may consider when assessing acceptable uncertainty. The guidance will outline how certain issues could be ultimately resolved in the post-market setting, rather than the pre-market setting, to allow patients to gain faster access to potentially life-saving devices, when appropriate. Under this form of more progressive review, FDA will outline how it makes judgments about when it’s appropriate to place greater reliance on post-market data in order to facilitate access to certain innovation, or when the agency needs to rely more on pre-market data collection because of certain issues related to a particular product or how it may be used.
This approach will be outlined in a new draft guidance that relates to the acceptable levels of uncertainty that FDA can accommodate in the pre-market setting relative to the public health benefits, and in turn rely on post-market data to answer certain questions. This balance is already a feature of product review across all of FDA’s programs. The new guidance is an attempt to make these considerations more transparent, consistent, and objectively-defined.
To further assess the impact of pre-market uncertainty, FDA may consider several factors. One is the extent of the public health need. Factors that may influence these considerations are the seriousness of the illness that the device will treat or diagnose, the size of the population that could benefit from a new innovation, and the benefit-risk profile of alternative therapies or diagnostics (if any exist). Another factor is how likely uncertainty can be resolved pre-market versus the post-market. FDA might accept greater uncertainty for a device where gathering extensive clinical evidence pre-market would not be feasible given the small patient population that the device is intended to treat. The likelihood that uncertainty can be resolved by collecting data post-market, such as through the use of registries, is another consideration. FDA must have confidence that it’ll be able to acquire required post-market data.
This approach to evaluating uncertainty could be used in any one of the existing pathways that developers must follow to market new devices – 510(k), De Novo, PMA, or HDE. That’s because these factors should guide our decisions about patient access to medical devices in any of the regulatory classifications. We’ll use our existing authorities to require more post-market data collection if we determine that’s the best way to resolve appropriate pre-market uncertainty for a specific device. And in all cases when this approach is taken, we’ll uphold the same standards for safety and effectiveness.
Looking Ahead to Other Device Policy in 2018
Although I’ve highlighted only two upcoming guidance documents related to FDA’s medical device review program, additional important guidance is forthcoming over the next several months, as outlined in FDA’s list of pending device-related guidance documents being published today. FDA publishes this list annually to provide transparency about our medical device regulatory priorities in the upcoming fiscal year. Several of the additional planned guidance documents, including the draft guidance documents regarding application of least burdensome and the Q-Submission Program, further demonstrate FDA’s commitment to advancing modern regulatory policies that are designed to promote medical device innovation, while continuing to assure the safety and effectiveness of new products.
Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration