By Michael Drues, Ph.D., President, Vascular Sciences
Approximately 10% of all medical devices enter the U.S. market through the FDA’s premarket approval (PMA) process, making it the second most-used U.S. pathway behind the 510(k). Since the PMA path is required for devices that are high risk (Class III) or for which no predicate exist, it is much more rigorous — that is to say, more complex and time consuming — than the 510(k).
Despite its onerous reputation, the PMA may actually be the most advantageous pathway for your device, and there are changes afoot within the agency that should help make the PMA path less for foreboding for manufacturers.
Advantages Of PMA
Although it is the most burdensome pathway to market for medical devices — requiring more in-depth benchtop testing and often computational testing, animal testing, and human clinical trials — there are several advantages of pursuing PMA.
Say you're bringing a new device onto the market, and it’s in that nebulous or gray area between the 510(k) and the PMA. It could go either way. Many companies would be tempted to simply take the 510(k) route, because it is the quickest, least risky, and least expensive way to get a medical device onto the market. However from a competitive perspective, you might be wise to consider setting the bar a little bit higher in going the PMA route.
Why? Yes, it will make your job a little more difficult. On the other hand, it will make the job more difficult for your competition as well.
So, if you're working for a large medical device company and your competition is a small company or startup, it actually might be to your advantage to set the FDA bar higher. This creates a sort of speed bump in the road, so to speak, causing your competition to really question whether or not they want to follow you. This is a technique I call competitive regulatory strategy. In my experience, most regulatory folks never think in these terms.
New PMA Guidances
The FDA recently released two draft guidance documents that might make the PMA pathway even more desirable for device makers.
One is called Expedited Access for Premarket Approval Medical Devices Intended for Unmet Medical Need for Life Threatening or Irreversibly Debilitating Diseases or Conditions, or Expedited Access PMA (EAP) for short. This guidance is basically a continuation of the FDA’s Medical Device Innovation Initiative of 2011, which was designed to help speed the development of the most novel products. These are not me-too devices, as many new products — even in the PMA world — are. Rather, the EAP’s goal is to help bring truly innovative new products to market that address unmet public health needs.
The other guidance is called Balancing Premarket and Postmarket Data Collection for Devices Subject to Premarket Approval. It provides additional detail in terms of what clinical data is required for a manufacturer to submit prior to PMA, as well as what data needs to be collected as part of the post-approval studies (i.e., postmarket surveillance).
The crux of this guidance is not only to provide manufacturers with additional information, but more importantly, to guide them in the thinking process. The FDA is acknowledging that there needs to be an appropriate balance between safety/efficacy and timely access to new medical technologies. Two sentences from the guidance (borrowed from FDA’s Benefit-Risk Guidance) capture this thinking: “there is never 100% certainty when determining reasonable assurance of safety and effectiveness of a device. However, the degree of certainty of the benefits and risks of a device is a factor we consider when making benefit-risk determinations.”
The time and cost necessary to obtain close to 100% certainty would be prohibitive both to companies and to patients waiting for new therapies. There needs to be enough regulation to ensure that only reasonably safe medical products get onto the market, but not so much that it inhibits life-saving or –improving new products from reaching the patients that need them.
I should point out that the quote from the new data collection guidance says “when determining reasonable assurance of safety and efficacy” — that is right out of the Code of Federal Regulation (CFR). One of the principle differences between regulations for medical devices versus drugs and biologics is that drugs and biologics are required to demonstrate substantial evidence of safety and effectiveness, whereas medical devices need only show reasonable evidence.
The difference between the words “reasonable” and “substantial” may seem like nothing more than a matter of semantics, but practically speaking, nothing could be further from the truth.
Making PMA More Attractive
In issuing these and other PMA-related guidances, the FDA is trying to encourage device makers to take the PMA path and bring truly novel devices to market.
Many companies are hesitant to take a regulatory pathway for which there is very little or very vague information. Few want to be the first through the doors at FDA with a new technology — for all the obvious reasons, not the least of which is the unknown regulatory pathway.
(As an aside, I personally love being the first through the door of the FDA, because it gives me the opportunity to get the FDA — or any regulatory body, for that matter — to think the way that I want them to think about a therapy. If I'm the second or third or fourth through the door, and I want to do something different than the predicates, I have to make the case that what they did was inappropriate or perhaps even wrong, and what I want to do is better. That’s a much harder sell.)
Unfortunately, some people have criticized the FDA for spending their time and resources putting out information on the PMA, which is not the most commonly used pathway to market in the medical device world. They say the FDA should be spending more of its energy on the 510(k), since it’s the path the vast majority of manufacturers use. I understand the reasoning behind that argument, but I personally find it to be very unfortunate.
The number of 510(k) submissions exceeds the number of PMA submissions by about a factor of 200. Although 510(k) medical devices are certainly important, they are basically iterations on a current therapy. Devices that gain 510(k) clearance are not taking major steps in a new treatment direction. They are slightly different versions of a product that we already have.
As a general rule, PMA devices are often revolutionary, life-changing products, often in an area where there is an unmet need. Sooner or later, our family members, our friends, and even ourselves will be on receiving end of these medical devices. I hope there are enough companies out there willing to take the path of greater resistance, for the greater good.
The Future Of PMA
Will these recent efforts by FDA have the desired effect, increasing the number of PMA submissions and bringing more novel devices to market? Only time will tell.
I don’t believe that the creation of just a few more guidance documents will, by itself, overcome the resistance that many in this industry have to investing the additional time and money necessary to developing PMA-type products. On the other hand, I do think it takes us a step in the right direction. Once again, it is the balance between regulation and innovation that we are trying to achieve here. I don’t know exactly where the fulcrum should be located on that seesaw, but I think that if we all are willing to work together, we can figure it out.
For those in the medical device industry who want more information and more direction in navigating the regulatory seas, this PMA guidance may help. But for those who prefer to work in areas where there isn’t as much regulation — because it gives them more opportunity for competitive advantage — the additional guidance may actually work as an impediment.
Editor’s Note: If you are interested in learning more about the PMA pathway, Dr. Drues is teaching an online course called The Premarket Approval Pathway: Ensure Successful Regulatory Submissions on June 4, 2014.
About The Author
Michael Drues, Ph.D., is president of Vascular Sciences, an education, training, and consulting company offering a broad range of services to medical device, pharmaceutical, and biotechnology companies. He has worked for — and consulted with — leading medical device, pharmaceutical, and biotechnology companies ranging in size from start-ups to Fortune 100s.
Drues works on a regular basis for the U.S. Food and Drug Administration (FDA), Health Canada, the U.S. and European Patent Offices, the Centers for Medicare and Medicaid Services (CMS), and other regulatory and governmental agencies around the world. He is also an adjunct professor of medicine, biomedical engineering, and biotechnology at several universities and medical schools, teaching graduate courses in regulatory affairs and clinical trials, clinical trial design, medical device regulatory affairs and product development, combination products, pathophysiology, medical technology, translational medicine, and biotechnology.
He received his B.S., M.S., and Ph.D. degrees in biomedical engineering from Iowa State University.
Image credit: Seal Lumen Red Icon Stamp Outline Symbol by Nemo 2012, used under a CC0 1.0 Universal license: http://creativecommons.org/publicdomain/zero/1.0/deed.en