Luke Herbertson, Ph.D. (LH), is a biomedical engineer in the Fluid Dynamics Laboratory at FDA’s Center for Devices and Radiological Health. The lab is interested in problems involving fluid flow, and the fluid interactions between medical devices and the human body. Dr. Herbertson recently spoke with Rob Fraser (RF), ViVitro General Manager, about his research and regulatory work at the FDA for our Cardiovascular Pioneers series.
RF: What is a normal day at the FDA like for you?
LH: My typical day here involves a combination of doing regulatory reviews as well as research. Regulatory science requires working closely with collaborators from academia, industry, as well as other government agencies, to solve issues encountered by the biomedical community. Most of my research takes place in the labs, where I develop test methods for studying fluid flows through medical devices. We have research interns working at FDA laboratories, just like in academia.
In terms of the regulatory work I do, my expertise is primarily in cardiovascular fluid mechanics. Different types of medical devices with blood-contacting components often come to my desk, and my reviews will typically focus on the portion of the submission that pertains to blood cell damage and flow performance.
RF: On one hand you are a researcher and on the other hand you conduct regulatory reviews. Roughly, what is the split between those two activities?
LH: It varies depending on the day. I tend to schedule laboratory research around the more urgent regulatory deadlines. A typical day might require me to focus 60 percent of my time on regulatory issues and 40 percent on research. Some of my research involves developing or updating methodologies for assessing safety and efficacy of medical devices that are already well established and on the market, and some work goes into establishing new guidelines for devices or emerging technologies that we anticipate coming on the market in the near future. The FDA must be able to adapt to unforeseen issues or outbreaks that suddenly arise. We also have long term research program areas, which span multiple device types where we recognize the problem isn’t going to be solved overnight.
RF: As a reviewer you mentioned anything that is contacting blood might come across your desk, are there common mistakes that you see or any advice you want to give?
LH: We encourage device manufacturers to engage with FDA as early as possible. FDA can work with companies to develop an individualized strategy for evaluating their device and preparing their regulatory submission. In some cases, it could be a good for a company to approach the FDA when they have a good idea or a clear picture of what their device entails, but maybe they are still making modifications to it. It is important for the company to not only perform the correct tests, but also to perform them appropriately, so we can work together to get the best possible medical devices out to the American public efficiently. We work very closely with standards groups and we also develop our own guidance documents to have a recipe or step by step process for companies to follow to get their devices on the market in a least burdensome manner.
In terms of blood damage testing, we see a lot of variability with the test setups and protocols before the devices are even integrated into the circuit. Our goal is to simplify the process and minimize the variability associated with those test methodologies. It is important for companies to evaluate their devices across their entire operating ranges, or to justify a worst case operating point. We often recommend for blood damage testing to be performed in a paired fashion with a comparator device which has a known clinical profile.
RF: From what I’ve seen at conferences, I think the FDA is doing a pretty good job of getting that message out to people. Come talk to us as early as possible. And I think that seems to be working for a lot of people.
LH: The Center for Devices and Radiological Health is currently undergoing a reorganization. We’re always looking to improve upon our efficiency both in terms of time for getting decisions back to companies as well as asking for specific regulatory questions. We certainly don’t want the company to be performing tests that aren’t going to provide us with useful information about the safety and efficacy of the device. We’re trying to be more transparent than ever before and ask good regulatory questions. We want to make the process as least burdensome as possible to companies. The more we can learn about devices on the bench, as opposed to relying solely on more time and cost intensive animal studies and clinical trials, the better. We want to tease out those potential issues with the medical devices as early in the total product lifecycle as possible.
RF: Can you give any more details on the reorganization that you mentioned.
LH: The Center is in the process of transitioning right now to a new organizational structure. We’re constantly getting feedback from the industry, patients and healthcare providers. The consensus is that the regulatory consistency, flexibility, and efficiency will improve if we go towards a more total product lifecycle organization where we have better communication between the preclinical side and the post market side. This will enable us to have a better understanding of devices from their development through their commercialization.
RF: Can you tell us more about your research activities?
LH: Certainly, my work involves studying flow related blood damage issues with medical devices. We recognize the potential for mock circulatory loops to be used as a valuable tool for learning more about devices during their pre-clinical stages. In my research, I’m trying to bridge the gap between preclinical testing and clinical outcomes by developing more meaningful test methods for evaluating cardiovascular device types, as opposed to evaluating specific devices myself. We’re looking for better and simpler ways to simulate real world clinical performance through preclinical testing.
There are no standard test methods for assessing flow performance through or around cardiovascular devices at this point in time, so my research involves working to develop a clinically relevant pulsatile environment using a mock circulatory flow loop capable of characterizing a number of different devices including blood pressure monitors, ventricular assist devices, and hemodynamic monitoring devices. The goal is to have an automated system to quickly and reproducibly evaluate devices at different operating points while simulating a range of patient populations and disease states.
We hope to reduce the need for extensive animal testing and maybe reduce reliance solely on clinical data in certain circumstances to characterize more complex medical devices.
RF: Has ViVitro Labs helped you in setting up that test apparatus?
LH: The ViVitro pump has allowed us to create a versatile physiological flow system so we can quickly recreate and quickly evaluate devices including blood pressure monitors across their entire operating ranges. The pump can simulate worst case conditions that might not be achievable in animals or clinical studies. We’re using a number of different input waveforms, some supplied by ViVitro and some created in house, to generate meaningful pressures and flows with the ViVitro system.
RF: You mentioned blood pressure monitors, does that apply to all of these new wearable medical devices? I think there are a lot of companies that are traditionally not medical device companies that are trying to figure out things like blood pressure monitoring in a say a smartwatch.
LH: Yes, we’ve created an arm phantom here for that exact purpose. We hope to be able to tell companies specifics about different size patients they might have to look at, different ranges of blood pressure, and how to display information and alarm if necessary. I believe there is much unexplored potential for using pulsatile mock flow loops as an evaluative tool. We’ve just started to scratch the surface of the capabilities of these systems, and combining in vitro circuits with validated computational models will only speed up the entire process.
RF: Yeah. Once you have validated your model there is huge power in computational models. You can easily test a wide range of variables compared with bench tests.
LH: Exactly, the use of validated computational models can expedite both the product development and regulatory processes. So if we perform a number of computational simulations on a particular device and then we focus on assessing specific conditions with bench testing, there’s a real advantage there.
RF: Do you have any other advice for our readers? Whether they are on the research side of things or more on the regulatory side or both of those camps?
LH: I just want to get across that the FDA is really trying to communicate the best we can with industry, focus on collaboration, and really take a least burdensome approach. A lot of people don’t know that the FDA does research. But we’re very open to collaboration and we try to perform high impact research that is going to improve how we review well established devices as well as keep up with emerging technologies.
We should always keep patients in mind through the whole total product lifecycle of the device. We’re very supportive of patient centric initiatives. And lastly, we highly encourage companies to come to the FDA early and often, and to not be afraid to share information with the FDA. The more we understand about the device, the more we can help a company navigate through the regulatory pathway and get high-quality devices to Americans faster.
Read about other Cardiovascular Pioneers here.