By George K. Lewis, Ph.D., ZetrOZ Systems
The medical profession continually strives to improve the care it provides, a process that benefits everyone. Advances in treatment protocols and technologies help providers take better care of their patients and furthers understanding of the science of healthcare. The medical device industry, in particular, is constantly innovating.
Before products can be marketed and benefit the public, of course, they must be reviewed by the Food and Drug Administration (FDA). Understandably, navigating the complexities of the FDA’s approval and regulatory process for medical devices can be daunting for all companies and particularly stressful for new technologies with disruptive innovation.
However, the FDA is best regarded as a partner and not an obstruction in this process. If device developers do their homework — and can invest substantial time and money — then working with the FDA can result in changes that benefit everyone.
The Long And Winding Road
My company, ZetrOZ Systems, grew out of a long family history in ultrasound device development and later research conducted in the early 2000s during my doctoral program at Cornell University on optimizing the therapeutic benefits of therapeutic ultrasound treatment. The essential concept is that a longer duration of daily ultrasound treatment provides regular activation of the soft-tissue healing cascade and, as a result, better patient outcomes. From the many years of our research on brain tissue, muscle tissue, tendons, and ligaments, we developed a unique ultrasound treatment algorithm called long-duration continuous ultrasound to provide sustained healing of tissue. By 2008, we had expanded the efficacy profile of ultrasound treatments beyond current technologies in the healthcare system, and we knew we wanted to commercialize the technology, so we founded ZetrOZ.
In 2010, we started capturing the necessary clinical and testing data, and that process continued until 2013, when we submitted our formal application with the FDA to enter the United States healthcare market. Throughout 2013, we were in the review process and there was significant back and forth with the agency, with information requests, replies, feedback, and more responses. We got our clearance in late 2013 and finally went to market in early 2014. It took three years of vigorous work building up the safety and efficacy testing we needed to get the device into the United States market. Those three years before our application submission were crucial, as was the application period itself.
Building The Right Team
Our strategy has always been to assess our internal team, our capabilities, and our strengths and weaknesses and do what’s called “red light, yellow light, green light.” We go through our submission and say, “OK, we’re strong here; however, in this [other] area, we know we’re safe, but we’re not strong here from our scientific background.” For example, we were the experts in ultrasound and ultrasound mechanism of action and in the use of ultrasound for drug delivery. We were not experts in the various testing standards for skin sensitization and biocompatibility. Some might call those cookie-cutter tests, but you have to make sure you do the cookie cutter right. In our case, we brought on expert laboratories and scientists with experience bringing devices that require such testing to the agency.
You build a bullpen of people to help you produce your submission and answer questions. But we’ve always managed the whole process ourselves, bringing in expert value when needed to supplement what we have internally on our staff.
This may seem contradictory at first, but there is a fine distinction.
First: You are the expert. You have to know that you are going to be integral in the submission process, providing the answers and the responses to guide the agency to an understanding of your product and why it's safe and effective.
Second: It’s vital to get a lot of external thoughts and reactions from people with their own areas of expertise.
Device developers — and businesspeople in general — tend to bring on consultants, thinking they will solve all your problems. That’s the wrong way to think about it. Consultants may have great experience and may have succeeded with different products, but no one is going to know your invention and your medical treatment like you and your team. Being even a couple of steps removed from your research can make it difficult to provide the accurate information needed for the authorization.
That said, there is enormous value in bringing on people who have been through the pitfalls and the successes in positioning submissions to the agency — the questions and concerns are very similar across various products and pharmaceuticals. We always found it helpful to have people who had been on the other side of the aisle, at the agency, doing these reviews, to understand how they are looking at it.
Some will be scientists and consultants, from the medical device side and the FDA. They can weigh in on concerns or questions and help you focus your submission, so it is logical and accurate, and ensure it has all the details but doesn’t go off on tangents. FDA reviewers are just like you and me: They may have engineering degrees or Ph.D.s, but they are not experts in your field. You want to speak at their level, but you don’t want to go over their head and confuse them.
Like professional athletes, each has their own way of preparing for the game. Each company and its team has an approach that works for them in working with the agency. There’s not a one-size or single approach; like an engineering problem, there are a lot of ways to come up with a solution.
How To View The FDA As A Collaborator Rather Than The Enemy
Sometimes we take for granted that the agency understands our technology as well as the scientists and engineers who develop new medical innovation. It is important to provide education and evidence from the ground up so evaluators can appreciate your responses.
Therefore, my advice for pursuing and receiving approval from the FDA is to see the agency not as an obstacle to circumvent but as a potential ally to enlist. Its product evaluation and quality staff are not your partners; they are objective arbiters whose ultimate mission is to advance healthcare while also ensuring patient safety. But like any neutral party, they can come to support you if you have a persuasive argument.
After our three years of clinical research and a year of review, FDA cleared ZetrOZ’s Sustained Acoustic Medicine (sam) device for marketing in the United States. When FDA provided our clearance, it came in a new category of devices, stationary ultrasonic diathermy. Our years of research and documentation proved that there was a significant difference between our sam platform and what was already available in the FDA device database, mandating the creation of the new category. After our clearance, the agency recategorized two older existing devices as stationary ultrasonic diathermy.
Since 2013, more than 20 level I-V clinical research studies, randomized placebo-controlled trials, and other articles have been published about ZetrOZ’s technology, on its efficacy in treating back pain, arthritis pain, strain injuries of tendons and ligaments, recovery, range of motion, strength, and soft tissue healing. In 2020, ZetrOZ received clearance for sam for prescription home use approval. For this clearance, we had seven years of use in the United States healthcare system demonstrating that the device was being used safely and effectively by thousands of patients and providers. But those seven years of evidence only were possible because of the many years of research and effort we had already put into the product’s development stage.
FDA’s creation of this new device type is just one example of how the agency can and does respond positively to innovation. It indicates that the agency sees a new category of devices that add value to healthcare by successfully addressing a medical need. It is worth noting that it also is to the agency’s benefit because it reduces the administrative burden on its staff.
Do your work. Dream, research, collaborate, innovate, and improve your work. Take the time and make the investment in your product. And then be patient. Educate, listen, and answer questions and be willing and prepared to do more work.
Remember, while it seems like the regulatory system may be a roadblock hindering your progress, both you and the agency have the same goal: improving the science and the quality of healthcare.
About The Author:
George K. Lewis, Ph.D., is the president and CEO of ZetrOZ Systems, a medical device company headquartered in Trumbull, CT and global leader in non-invasive soft tissue healing technologies. He currently serves on the Veterans Health Administrations Research and Rehabilitation Review Board and on the Orthopedic Foundation Board of Directors, and he was previously a Presidential Life Science Fellow and a National Science Foundation Fellow. A prolific author of peer-reviewed articles, he has also filed over 60 global patents and has raised millions of dollars to support healthcare innovation commerciality. He earned his degree in biomedical engineering from the University of Miami and his doctorate in biomedical engineering from Cornell University.