Scientist to Regulatory Lawyer: Getting Medical Devices to Market

Kyle McEntee:

We're joined today by Randy Prebula, a partner at a global law firm who specializes in the regulatory world of medical devices and technology. If someone took a look at your CV, they'd notice quite the gap between when you finished college and started law school, more than 20 years. What were you doing before law school?

Randy Prebula:

I was a scientist. I got my undergraduate degree in microbiology, my graduate degree in immunology, and I bounced for a number of years between a number of different firms. I worked on designing tests to help look for diseases like HIV, and I helped develop vaccines for children to avoid them having diseases that we didn't want them to have.

And during that time, many of the companies that I worked for had outside legal representation. One of them, actually the outside lawyer for the company contacted me whenever the company was being bought and said, hey, I know what you do. I know what you know. I know how well you write. Would you like to come help support my law firm as a scientist?

So that's how, after that long period of time, I transitioned from being in industry and biotechnology and product development and product manufacturing and quality control into a law firm environment, basically explaining science to lawyers and regulations to scientists.

Kyle McEntee:

Were you in law school part-time then, or did you take the time off?

Randy Prebula:

No, I hadn't gone to law school yet. I came to work for the firm that I'm currently working for in 1998 as a scientist. I did not go to law school until 2006. The firm started asking me in 2004, would you be interested in going to law school? And when they asked me again in 2005, I said, well, would you help me go to law school? And they said, we can do that.

And they came up with a method by which they would help support me partially through law school, and I would commit to staying with them for a number of years after law school, and it would be a mutually beneficial relationship. So I went to law school in 2006, night school. I graduated in 2010.

After I graduated, they started me out at the counsel level instead of an associate level. I'd already been with the firm for a dozen years at that time point. They knew my background. They knew what I was doing. They knew that I understood not to commit malpractice. I'd been working under the direction of lawyers for a very long time. And all that time, I was doing regulatory work, not legal work. So any time a client would come to me and say, I know you explained the science to me. I know you explained the regulations to me, but what happens if I don't do that? I'd always say, that's a legal question. Let me get a lawyer for you.

So that dichotomy was really important because that's the way the firm operates.

Non-legal professionals provide non-legal support. Legal professionals provide legal support. And I always worked under the direction of a partner. So I became a partner in 2014, and that's a very non-traditional path and a non-traditional timeline. I realize that. But the firm felt that I'd earned the opportunity.

Interestingly, after I became a partner in 2014, the gentleman who hired me in 2019 said, I really want to stop being an administrative leader for the firm. I'd like to step back and just do law. So I'd like you to take over my role as the practice area leader. So not only was I helping clients, but I was also supervising other lawyers and organizing what we did as a practice. And I just turned that over to another partner in November of last year. So I continued to operate as a lawyer, but I'm no longer in an administrative position as well.

Kyle McEntee:

So you have a lot of support from the firm as you're making the transition from scientist employed by a law firm to eventually becoming a lawyer employed by the law firm. Did that decision feel like a big risk to you at the time? Or at this point, was it just feeling like the obvious choice?

Randy Prebula:

To me personally, it felt like the obvious choice. I had been advising lawyers on the regulatory aspects of what we did for the entire time with the firm. I was able to see the legal questions that we were trying to answer.

I had a feel for how to communicate where the regulatory agencies, the Food and Drug Administration, others in other jurisdictions in Mexico, in Argentina, where they were drawing the lines. And while I certainly don't practice law in those jurisdictions, I can help explain how the regulations apply to U.S. companies. So to me, the transition from being a scientist to a lawyer was just a natural progression of where I was. I'd never considered it ahead of time. Again, I wanted to be a pediatrician, but it was the right step at the right time.

Kyle McEntee:

I think when people think about regulation in the healthcare space, they're often thinking about new drugs. But that's not all that the Food and Drug Administration, or FDA, regulates in healthcare. Can you give me like a 40,000 foot view of the government's approach to devices, starting with what a device even is?

Randy Prebula:

Well, medical devices are very broad. They can be things like hip implants or knee implants. They can be pacemakers to keep your heart working. They can be tiny stents to hold blood vessels open, or the alternative, clips to close them when you have an aneurysm or a weakness in the veins or the arteries in the brain. Sometimes you need to close those off to keep somebody from having a rupture and a stroke. And those are medical devices. Those are things that go in the body that do something physical, not chemical. So in a nutshell, anything, glasses, toothbrushes, surprisingly, toothpaste, they're considered medical devices because they act on the body in a physical way instead of a chemical way.

Kyle McEntee:

And there's some kind of claim associated with it, right?

Randy Prebula:

Yes, there's a medical claim associated with it is you're doing X to treat Y, or you're running this test to diagnose COVID. Diagnostic tests are medical devices. I guess the easiest way to look at this is that drugs and biologics, drugs are things that are given to the body that act chemically in the body to treat a disease.

Biologics are things derived from the body, like blood or vaccines, or things that are grown outside the body that are given to the body to stimulate or to change the body's response. Medical devices are physical things that are put in or on the body to help address some medical condition. They have to be tied to some medical condition, otherwise they would be consumer products.

Kyle McEntee:

So earlier you mentioned that you're doing something a little different now. You were wearing a scientist hat, now you're wearing the lawyer's hat. How did that actually change the conversations you were having? On the one hand, it means you weren't sending them to a lawyer. You were the lawyer.

Randy Prebula:

In a nutshell, it broadened what I do. I still do the science. I still explain what it means to be a vaccine or a biologic or a drug or a device. So my becoming a lawyer meant that I got to answer all the legal questions that I couldn't answer as just a scientist, but with my background, I get to bring the full of what I know to my clients. And not everybody in my practice is one or the other. Many people are technically trained, but you don't have to be.

I work with many lawyers that are excellent lawyers that understand how the regulations are applied. They understand when FDA uses or potentially abuses its authority. It works with the regulators to say, hey, wait a minute, where are the lines really drawn here?

We get to help influence how FDA expands the scope of the law by showing them where their precedents have some boundaries. And I get to do that on the science end as well as the legal end.

Kyle McEntee:

So what are the channels of influence for you then? Are you doing it through litigation? Are you doing it through conversations with people at FDA?

Randy Prebula:

All of the above. And let me give you an example of that. Sometimes we help clients write responses to notice and comment rulemaking. That's where FDA says, I'd like to do something here. This is what I think. Provide comment back. We write with our clients and help them submit those comments. Sometimes we write them on our own and submit them on our own volition. So that's where we're actually influencing future legislation.

We help draft legislation. We've provided FDA draft legislation. Some of it's been enacted in part in some areas. Some of it's not been enacted in part, but we're part of the dialogue. We do it through submissions. A company says, my product is very much like this product. It's a slight stretch, but here's why that stretch is appropriate. FDA sometimes agrees and expands the scope through approving that product. Sometimes they disagree and say, here's an alternate pathway to become a new product in this area.

Sometimes they say flatly, no, and there's litigation associated with that, appeals. Appeals lead sometimes to litigation. I've supported litigation as well.

Sometimes it's going to FDA and providing them comments internally on an area where they ask us to come in and consult with them. Our firm also provides people to help FDA in their own internal training. What do the regulations say and how are they applied? FDA hires people from outside the government to help provide training to their new employees, obviously under their review and oversight. So we get to influence FDA and be influenced by FDA through all of those pathways.

Kyle McEntee:

So what are some of the reasons that a company is coming to you for help? And can we walk through a specific example kind of from the time they walk in the door to phase three approval?

Randy Prebula:

I'm not going to mention this company by name, but the company had developed an implant, a pin, a screw, a nail, something like that that would go into a part of the body to hold the bones together after they'd been fractured. And they designed their implant not to be put in and left forever, some companies do, or to be put in and after the bone had healed, be taken out surgically. They designed their product so that the product would biodegrade within the body over time, so that after the joint had healed, after the bones had healed and been fused together again to prepare the fracture, eventually the nail would just go away. And they came to us because they wanted to market their product. And they told FDA, we think we should be found what's called substantially equivalent to this other nail. They remove theirs; ours removes on its own. It's not a big difference. And FDA said to them, and they came to us before we submitted this, it was really a novel product. Dissolving on its own over time is something no other product had ever done.

Kyle McEntee:

Yeah, I'm a little sympathetic to that. I'm sitting here thinking, I kind of want to know what happens to something that is alleged to dissolve. What are the consequences to that, right?

Randy Prebula:

That's a good question. The short answer is usually it's metabolized by the body and it goes away. This particular device, as it metabolizes slowly, also releases a tiny amount of gas. And FDA was concerned that that gas would interfere with healing. So what they did was they said, there's this pathway between, I'm gonna get a little technical here. FDA allows products to come to the market that are really simple, like stethoscopes, without prior FDA approval. As long as you're making a stethoscope to do what a stethoscope does, all you have to do is tell FDA, I'm gonna market it after you start marketing it. Call it an exempt product. And there's a whole class of simple products that go like that. The next level up is where you say, I am just like something else you've already cleared, you've already marketed. That's called the 510K, named after the part of the statute to where it comes from. It says, if I'm just like them, and I don't raise different questions of safety and effectiveness, I have to test it, I have to prove that, and I have to get your permission, but I don't have to test it in thousands of people. I can show that I'm just like something that's already on the market. And it's not a loophole, it's not a shortcut. It still requires testing, it still requires showing that it's biocompatible with the body. And that's where my client wanted to be with that product. I'm just like something else. And FDA said, you have a novel feature.

And FDA has a pathway for devices that are mostly like something already on the market, but has some novel feature. And it's called the de novo, or brand new, approval. And de novo approvals were created in 1997 as a pathway where you have a low-risk device that has some novel characteristic to allow it to come to market without testing it in thousands upon thousands upon thousands of people.

For really risky products, FDA has a pathway for that. It's called the pre-market approval pathway. And it requires much more testing. So we helped our client defend why they belonged in that new category that has lower risk. It's a low to moderate risk product where testing can show that it works. And FDA agreed to that.

Now, it took two years of human clinical studies to show that as it dissolved, it didn't cause harm and that the gas that it generated didn't impede healing. And FDA said, you've tested it enough. You've provided us the data. We agree with that approach. You become the first of a novel class of products, bioresorbable implants.

Kyle McEntee:

It sounds like your previous role was really, “let me understand what you're trying to do so I can know how to tell the lawyer what you're trying to do so that way they can figure out which set of regulations apply and in which way.” Now, as the lawyer, you're able to do both because you can understand what's being said, how it applies, go to the statutes, go to relevant cases, case law or administrative rulings or whatever, right? And then figure out, okay, here's how I can give you advice for how to move forward. Here's what you can expect to hear from FDA. And it helps you sort of set expectations and those expectations for these companies that are often raising a lot of money and making promises to investors that we're gonna get this approval in three years or two years or one year. And that makes a big difference in terms of runway.

Randy Prebula:

It does. The valuation of the company is part of what we have to help them address as well. I want to be really clear, however, that I do my work both as a scientist, as a lawyer, predominantly in the area of regulated products, but I also support our firm with mergers and acquisitions and evaluating whether somebody's an appropriate target. Have they followed the rules appropriately?

I also support litigation. I had a case when I was only a scientist at the firm where one of my litigation partners called me at the time and he said, Randy, I have a question. Please tell me, does the blood circulate one way through the body or in two directions? And I said, really simple answer, one direction only, always one direction only. And he said, oh, you ruined my case. I said, no, I saved you from making a fool of yourself.

So while it's a fraction of what I do, probably 80 to 90% of what I do is regulated products, it's not just science in the context of getting the product on the market is making sure that it causes no harm, that it fits the entire regulatory framework. And sometimes it's just answering a simple question from a litigator, what's possible, what's not possible from a physical perspective.

Kyle McEntee:

You know, that 10, 15, 20% of your time you're spending with M&A lawyers and commercial litigators, that other 80% or so, who are you working with primarily inside of your firm? What's the team like?

Randy Prebula:

Our firm has 16 regulatory practice groups, everything from pharmaceuticals to food, to government contracts, to transportation, to privacy. Of the 16, I think I've worked with all of them. Within our corporate practice, we have corporate M&A specialists, we have finance specialists, we have individuals who are looking at somebody to review an SEC filing, a filing that the company has to file to be able to become a company. We review those documents with them. We provide insight as to whether the way they're stating the regulatory laws are appropriate.

Kyle McEntee:

I think it's fair to say that a big part of your job is acting as a translator between regulators, scientists, product designers, and lawyers. Where do things most often break down when people aren't speaking the same language?

Randy Prebula:

I think it's when people don't take the time to stop and listen and say, let me repeat back what I think you're saying. Do I really understand what you're looking for? Regulators, companies, litigators, the courts often assume they understand before they really do. They draw conclusions before it's really, they have enough information to draw valid conclusions. Correcting that or resetting that and starting the dialogue over again is essential to avoiding those types of errors. Being thoughtful, I'm not always going to be right. Somebody may say, yes, you're right about that, but you haven't realized this other issue that I'm concerned about. Listening carefully, the same applies in both of those contexts.

Kyle McEntee:

Can you give an example of a case you worked on where your ability to bridge these worlds really paid off?

Randy Prebula:

The case I'm most proud of working on where I got to bridge the science and the technology was helping get the first at-home COVID flu tests to the market. It was a test that didn't have to go to a laboratory to run. It was just as good as a laboratory test and it was done within 30 minutes at home and FDA authorized it. It was the very first product that was authorized for at-home testing of that type.

Kyle McEntee:

What's interesting to me is your line of work is public health. It involves a lot of urgency and the regulatory process at FDA can be slow or deliberate, depending on your point of view, because it's life and death on either side. The people who want to put a new medical device out there or a new drug therapy, they're wanting to improve or save lives. On the other side of it, the regulators want to protect people from false claims, from products that don't work or that do more harm than they promise. Can you talk a little bit about how COVID impacted timelines for your clients? We saw live out through our experiences just a few years ago.

Randy Prebula:

FDA for many years has had the authority to respond to emergencies through emergency applications. Think about during the war on terror and after 9-11. There was a real risk that there were going to be dirty bombs and dirty bomb being a bomb that exposes radiation to individuals by dispersing radioactive material over an area.

Responding to that, Congress gave FDA the authority to approve emergency products when a national emergency, when a national health emergency existed. West Nile virus was an example of that. Zika was another example of that. Ebola was a potential concern in the United States whenever there was an outbreak amongst monkeys at a laboratory. If any of those things were to happen, FDA has the authority, the Secretary of Health and Human Services has the authority to issue an emergency declaration. There is an emergency. When there's an emergency, products that are used to help reduce the risks of that emergency can be expedited. They can be reviewed on lesser data than they would normally be because the benefit of the product outweighs the risks presented by it. FDA's authority in every product, drugs, biologics, medical devices, foods, they all relate to this balance of risk and benefit.

In a normal time when there's no emergency, you tolerate very little risk because the benefit is part of developing the natural development of products. It's about helping somebody get a better knee implant, but it's not like an emergency. The COVID example, because it was so immediate, it was so widespread, it involved things like taking respirators that were designed normally to work with adults and making sure they could work with pediatrics children that were dying because they couldn't get enough air into their body and adapting them and modifying them to fit that emergency need required lesser data than you would normally have because you would normally need to get a product approved because you had no alternative. You had to get something to them today. The testing for COVID, designing that testing, getting it out to the field, whether it was a home test or a laboratory test or getting a sample and figuring out how they work together, FDA couldn't say, give me, I'm going to use the term PMA, pre-market approval application, give me the proof that you tested it in hundreds of thousands of individuals and that its diagnostic accuracy is 99.9% because in an emergency like that, 80% is better than nothing. 90% is better than nothing. Getting a test that can be run at home within an hour is better than saying, come to the doctor, get on the Metro to go to the doctor, expose thousands of people. The emergency warranted that. FDA used their existing authority, not new authority.

Kyle McEntee:

So I think the role of the scientists and the companies, the biotech companies, the pharmaceutical companies is pretty clear in the emergency situation. They're trying to take what they know already and apply it to this new emergent circumstance. Can you talk to me about the lawyer's role in this?

How are you taking in what you're hearing from those companies and then figuring out how to translate it to FDA to say, the balance of risk is on our side here. We need that emergency authorization.

Randy Prebula:

I would say that early on in COVID, I was more the scientist than the lawyer because a lot of the time it was explaining to FDA the science. As the epidemic evolved and as technologies and what we knew about the virus shifted, it became more making sure that the lines were drawn properly. In the second year, it was probably 50-50.

In the last year, it was defending whether the emergency needed to continue, whether the transitioning from emergency application to other application was adequate, whether we had a predicate device, a device to compare it to, to allow us to bring it onto the market. It was more law because at that point, the science was robust. Everybody understood what was going on. Most people had a good idea what was going on.

Kyle McEntee:

So when you're making that transition, now you're doing the predominantly legal work, what does it actually look like?

Randy Prebula:

The research side is usually from FDA maintains exquisitely detailed databases of the products that they clear, approve, or authorize through emergency applications. And they're publicly available. They're usually publicly available on FDA's website within 15 days of an approval being issued. You research it. It's available to multiple technologies. With AI now, many of that is accessible through the searches. You can use AI. You can say, tell me how many products is FDA approved for COVID or how many products FDA is EUA authorized. And it'll about search it for you. Now with any good AI tool, you want to do the diligence to make sure the information you got back is accurate. That's a given. But having said that, it's a great place to start.

But I usually go to FDA's databases. They're a little harder to search because they're not set up like AI is set up. But FDA also lists products by what's called a product code. A product code is every product that works similarly is bucketed into this product code. Well, you search that product code and you find out how long they've been on the market, what type of products they include, how have they evolved over time. You do that by scrolling through them and looking at their approval documentation, which is often linked off of that.

So I use FDA databases. I use publicly available information. I look for publications through PubMed and Medline and other sources that talk about the disease and conditions. I always look back to how long has it been on the market.

I worked with a product once that was used to hold tissues together during surgery and their predicate device, the device that they were comparing themselves to had been on the market since 1896. It existed before FDA even existed. It was being used by doctors in the old west to hold tissue together. It was basically a button that you put through the tissue and held it close together. So we researched that and we researched that by going to, believe it or not, a Sears catalog from 1896 that described it.

Kyle McEntee:

So you get all this information. What do you do with that information as it pertains to the legal analysis?

Randy Prebula:

We have to describe to FDA both why it's relevant, how it answers the question that they have authority to ask, how it demonstrates that the product is either safe or effective or performs in the way we want it to do, that it's a valid comparison. We're giving you scientific data showing why we're like that and how it functions. FDA often very much defaults to does the practice of medicine, do doctors recognize that information and that approach is valid for those patients?

If you can show that what you're doing is similar to those products, is addressing the problem in a way that medical doctors accept is relevant, that you're not creating new risks to the patient, you have a more straightforward argument that it should be regulated in a particular way. So we synthesize that information. We look for everything that's known about the product and the product type.

Are there doubts in the literature? Does somebody say, you know, it doesn't work that well? An example of that is there used to be lasers that would be used to punch little tiny holes in the heart for people that had heart failure with the idea that if you created those channels, those little micro channels, the body would naturally allow blood to move into that space and create new blood vessels.

In theory, that's a great idea. In practice, it didn't work quite as well as people thought it was going to work. But testing it out and designing how to test it and showing whether it works or not and designing the clinical studies involved FDA and the companies and the scientists and medical doctors and lawyers to come together and say, this is how we should study this to figure out whether it's actually effective or not.

This is where the doctors shouldn't be testing randomly people without actually identifying, are they eligible for this? Is it reasonable to treat them with that? Is it not an unnecessary risk to enroll them? And drawing those lines comes partly from the statute, partly from the understandings of the science, partly from precedent, partly from medical knowledge. And it doesn't require a lawyer to synthesize it. It doesn't, but it requires a lawyer to help explain where the lines are drawn and why you fit within the lines.

I tell my clients all the time, don't just tell FDA what you did. Tell them why it was the right thing to do and how it fits within their framework for reviewing it. And that's what I do.

Kyle McEntee:

Well, that's fundamental to persuasion, right? Understand how someone's going to get information from you, how they're going to interpret it and then interpret it favorably.

Randy Prebula:

And listen if they have alternatives to why they have an alternative or why they have a concern and figure out how to help address that concern. I was on a project once with FDA and I won't give you the gory details, but it required testing cells taken out of a patient whenever they donated blood. And FDA said, we'd like you to test X number of those units because we just need more data. Why can't you just test some number of them?

And the client did a really quick mental calculation and said, well, given that there's only 1 10th of that number actually drawn for patient use in the United States every year, I would have to not have that legally marketed product available to treat patients for the next 10 years to do the study you want me to do. So either I can take 20 years to do it and treat half the people who need it or we need to find another way to do this.

And FDA has thought about it and said, what I asked for was unreasonable, let's work on it. So it's that understanding of the field and the patients and the amount of product that's used and understanding whether their question is relevant and possible, physically possible to do is part of having that dialogue.

Kyle McEntee:

Do you feel like that dialogue is what you can expect or is it not always the case that you get that active dialogue where you kind of feel like you're both swimming in the right direction?

Randy Prebula:

Not always the case. It's not always the case. To be clear, I think having that dialogue is successful somewhere in the 90 to 95% of the time range, just from my gut reaction and thinking back over the last 20 years of doing my work.

There are times when the FDA says, we understand your point, we continue to differ with you, here's where we're going to draw the line. And often that's in questions of jurisdiction. Is a product a device, a drug, or a biologic?

We think oftentimes the product should be regulated as a device because it seems to have a physical mechanism of action. And FDA says, great arguments, we understand why you believe that, we don't think you've demonstrated with enough assurance there could still be something you're overlooking. And we say, theoretically where? And they say, no, no, no, we still think it's possible. And that's where it's not frustration, it's just where FDA draws the lines. We understand that. We still try to work with them. We still try to educate them. We still try to hear what they're saying.

We're not always successful. Nobody's always successful. What I'd hope we've done is help create a broader body of knowledge so that in the future when we come back with more data, we can show them why we think we're right. And it's a dialogue. We want to continue to have it.

Kyle McEntee:

So you wanted to become a pediatrician very early on. You ended up going instead into medical technology and then eventually ending up at a law firm. Has your career scratched that itch for you of wanting to do something important in medicine?

Randy Prebula:

Yes, it has. A lot of people that I work with, lawyers mostly, tell me that I should never, I would have been a good pediatrician but never become one because I'd never get to sleep. And my answer is, well, we don't sleep either.

So I guess I've accomplished it. I'm happy with my career path. I'm very happy to have been given the opportunity to grow into the law and to be able to apply what I know and love in the context that still helps public health, but from a completely different perspective than I thought it would.