When most people think about personalized medicine they only think about drugs, but that term also applies to medical devices. Specifically, the 3D printing of a medical device—not for the masses—but designed and sized to fit a particular patient. While you may also think that those two processes would be separate, at least from a regulatory perspective, that is also not the case. It turns out pharma and medical device companies can learn a lot from each other when it comes to 3D printing.
Michael Drues, PhD is the President of Vascular Sciences, an education, training, and consulting company offering a broad range of services to medical device, pharmaceutical, and biotechnology companies. Michael has served as a consultant for the FDA as well as pharmaceutical and medical device companies working with 3D-printed technology. PM360 spoke with Michael about how personalized medicine applies to the medical device industry, the roadblocks holding back 3D printing technology in healthcare, why the regulatory approval process between a 3D-printed device and drug is not different, and what the future holds for this technology.
Personalized medical devices printed to fit each individual patient would still require approval from the FDA, and as we have seen in other areas within the industry people can be leery of pushing boundaries. Is there enough guidance for companies to move forward with personalized devices?
While medical device companies are very slowly beginning to stick their big toe in this water, it’s not happening nearly as fast as it could or it should for a bunch of reasons. You mentioned regulatory and the FDA. That’s certainly one. But there are other reasons as well.
Focusing on the regulatory side, just this past summer, the FDA finalized the guidance on 3D printing of medical devices. So to the FDA’s credit, I give them kudos for finalizing that guidance. On the other hand, it should have come out at least 10 years ago because nothing is new at all in that guidance. And unfortunately, in the absence of any guidance or regulation, most companies are not keen on being first through the door at the FDA with a new device or a new drug or a new technology. It’s an interesting phenomenon to me that having too little regulation or no regulation at all can hold companies back as much as having too much regulation. This is not unique to 3D printing, or even personalized medicine, I see exactly the same challenges in other advanced technology areas where I work such as tissue engineering or biomedical nanotechnology.
Do you anticipate that now that these guidances are out it will help move things along a little bit?
Well, I hope so, but only time will tell. Currently, somewhere north of 85 medical devices are on the market in the U.S. that have been brought through the FDA that are 3D printed. Additionally, last year the FDA approved the first 3D-printed drug. So simply put, some companies are not waiting for the FDA or anybody else to tell them what to do and are taking the lead. But those companies are very much in the minority. And I’ve said this publicly many times, if we as an industry wait for the FDA to tell us how to do something then we’re going to be waiting from now until the sun burns out.
You mentioned that there are roadblocks besides regulation. What else is holding companies back?
The technology itself is still pretty primitive, and that’s putting it politely. First of all, people use the phrase 3D printing in sort of a generic sense, but there are probably close to 20, if not even more, different technological versions of what goes under that umbrella of 3D printing. So, it’s not a one-size-fits-all kind of technology.
Second, of the technologies that people consider 3D printing today, all but one or two of them have not been developed for biomedical applications. On the contrary, they’ve been developed for other industries such as automotive or aerospace. And now we’re trying to retrofit or spin those technologies and make them work in medicine. It does not take a PhD in biomedical engineering to appreciate that maybe that’s not the best approach. Fortunately, we have a couple of companies that are working specifically to develop 3D printing technologies for biomedical applications. But, it’s taking a long time.
Another limitation under the same category of technology is materials. The materials that we have to choose from that are 3D-printer friendly are very limited. And only a small number of them are biocompatible, and really none are bio-friendly. So we need new materials that can be used with 3D printers.
One other limitation is on the reimbursement side, which is a whole other can of worms. And one thing I guarantee: Unless there’s a fairly well-defined reimbursement pathway, there isn’t a snowball’s chance in you know where of most companies pursuing the technology, regardless of how clinically beneficially they might think it is. At the end of the day, medicine is a business, and if nobody buys your product because they can’t get reimbursed for it, that’s a significant challenge.
But all of those challenges are solvable. None of them are deal breakers. But some of the challenges are not easy, and will require different ways of thinking and different ways of doing things, which, as an industry, is not something that we’re always willing to do.
You mentioned how there’s approximately 85 personalized devices out there in some capacity and one 3D-printed drug. Can pharma companies or medical device companies learn anything from each other about 3D printing?
Absolutely, sometimes you can learn what to do and sometimes you can learn what not to do, but you can definitely learn. One of the philosophies I’ve tried to develop over my nearly 25 years of playing this game is to try to look for similarities where no similarities seem to exist. One of the comparisons that I love to do is compare the regulatory strategy that we used to bring the first 3D-printed knee onto the market two years ago to the regulatory strategy that we used to bring the first 3D-printed drug onto the market just last year.
And to most people, they would think that there’s probably no similarities between 3D printing a device like a knee versus a drug. On the contrary, it turns out that not only are there are a lot of similarities, but the regulatory strategy is exactly the same. Many people in the FDA as well as outside of the FDA have said that we need a different regulatory pathway to market for personalized medicine of devices versus personalized medicine of drugs, but I disagree.
If we approach it from a regulatory logic perspective, which is a very uncommon approach, then the strategy that we used for the knee and for the drug are exactly the same. Of course, the details a little bit different, but the basic logic is the same.
Can you explain why that is?
Here’s the logic. Let’s talk about the knee first. What if I can show that the knee coming off of our 3D printer is basically the same as, i.e., substantially equivalent, as we say in the medical device world, to a knee coming off of our traditional manufacturing process? If I can do that, it is a huge advantage, because now essentially what I can do is totally remove the knee from the equation. In other words, I don’t have to say anything about the knee, and all I have to do is validate the 3D-printing process.
I can further mitigate my regulatory risk by, at least for the first generation of the device, limiting the surgeon to be able to print only knees that correspond to shapes and sizes that are already commercially available. Because if I can do that, then I don’t have to validate the size or the shape, because presumably somebody else has already done that.
So we get this, if you will dumbed down version of the product onto the market, and then we go back to the FDA at a future point, maybe a few months later, and we start removing some of these limitations. Now I’m going to take one of these criteria off, say the surgeon can print any size of knee that they want, as long as it’s between X and Y. Where do X and Y come from? I don’t just pull those numbers out of the sky. I look at the range of sizes of the knees that are already commercially available, and I pick the minimum and maximum. So again, I don’t have to do any validation. Somebody’s already done that.
Then we go back to the FDA a third time, and this hasn’t happened yet, but we basically relax those criteria even further, and say, “Now we will let the surgeon print any size that they want.” To use a baseball metaphor, this is the difference between swinging for a single versus swinging for a homerun. I would much prefer to swing for a homerun and incorporate all the bells and whistles into the product the very first time. But the problem is when you swing for a home run, you have a higher likelihood of striking out. Instead, swing for a single. Get the product onto the market in its dumbed down configuration, and then move from base to base.
In the regulatory vernacular, that’s what we call a label expansion. Interestingly enough, label expansions happen in the drug world all the time. It doesn’t happen quite as much in the medical device world, but I use label expansions a lot in devices.
So now let’s shift over to the 3D-printed drug from last summer. The logic is exactly the same. If I can show the active pharmaceutical ingredient (API) that ends up in the pill coming off of our 3D printer is the same as the pill coming off of our traditional tableting machine, then once again I can totally remove the drug from the equation—just like we removed the knee from the equation. All I have to do is focus on validating the new manufacturing technique. And I can further mitigate my regulatory risk with the drug just like the knee, at least in the initial configuration, by limiting the printer to print drugs at a certain dosage.
Once we get passed the regulation hurdles, as well as the other roadblocks you mentioned, what do you see as the future of this technology in healthcare?
First and foremost, 3D printing is truly a revolutionary technology, not an evolutionary technology. We’re just at the tip of the iceberg—what we’ve done thus far is child’s play. I mean, you’ve got to start somewhere, but where are we going?
On the drug side, let me pose this not so hypothetical scenario to you. You get sick, you go to the doctor, and the doctor writes a script. You’ve got to take two, three, maybe four different medicines to get better. So you take that script to CVS or wherever and they give you some pills out of a bottle and send you on your way.
But in the future, imagine instead of the physician writing you a script, that information is transmitted electronically to a little 3D printer in the back of the pharmacy, or better yet, in the back of the physician’s office and those pills are printed for you. And not just one medicine per pill either, but the combination of drugs into one pill at the dosage that you need. In other words, why the heck should some drug company decide how much drug to put in a particular pill? We’ve been practicing medicine like that for decades, maybe longer. But when you think about it, it makes absolutely no sense. I want the doctor to be able to decide how much of the drug, and not just how much, but how fast it comes out and so on and so on.
But I don’t want to just limit myself to giving a patient a combination of some existing drugs. Instead, I want to be able to actually design a new molecule, what we call the new molecular entity (NME), a molecule that does not necessarily exist in medicine, a molecule that was designed specifically for that patient, and have that printer make that molecule and put it into a pill and deliver it to the patient.
What would something like that mean for pharma companies, if you are able to print these NMEs in a physician’s office?
[Laughs] That’s a question that is probably making the top folks in several very large pharma companies a bit nervous. Interestingly enough, I see exactly the same dilemma for medical device companies, because as we’re able to print more medical devices on demand then you can literally print things as you need them.
But as I mentioned previously, if we can’t sell the economic model, then no matter what the technological or medical or regulatory challenges are it’s a moot point. So, how do we sell the economic model? It’s pretty simple, instead of focusing on selling devices, medical device companies can focus on selling or licensing the design of the device. Similarly, pharma companies, instead of selling pills will have to focus on the value proposition. So the focus is no longer on the pill or the device, but the process.
The last example that I’ll give you in terms of the future prospect for this technology, is in bio-printing—actually printing living tissue or perhaps even organs. It sounds like science fiction, but we’re making more and more progress in that direction.
While the most obvious application for that would be for tissue transplant or organ transplant, to me that’s too obvious. Instead, imagine being able to turn the way we do drug clinical trials totally upside down. Anybody familiar with the drug world knows that the way we typically do drug trials is we test it on the benchtop, we test it in animals, and then we test it in people. And we’ve been doing this for decades, if not centuries.
Instead we could go from what I call engineered human tissue testing to clinical testing. For example, companies could print tiny little organs—we can them organoids—such as a tiny little human liver that is genomically and biochemically identical to the liver in your body, and we expose our possible drug candidates to that little human liver. Not only could that make clinical trials more efficient, but it makes so much more sense.
Those are just some of the applications that I see as the future. Clearly there are challenges, but as I said earlier all of them are solvable problems. We just need to get people to think differently. And that’s not always as easy as it might sound.