Regulatory & Quality Perspectives of 3D Printing in the Medical Device Industry

What are the differences between 3D printing and additive manufacturing? What are the quality and regulatory considerations around 3D printing? What is FDA’s approach to whether or not this technology should be regulated?

In this episode of the Global Medical Device Podcast, Jon Speer and Etienne Nichols talk to Mike Drues of Vascular Sciences about the pros and cons of 3D printing in the medical device industry and key considerations manufacturers should make with regard to this technology.

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Some highlights of this episode include:

• Although additive manufacturing and 3D printing are often used interchangeably, Mike explains that 3D printing is a very broad category with at least a dozen different technologies under that category, including additive manufacturing.

• FDA describes 3D printing as, “a process that creates a three-dimensional object by building successive layers of raw material. Each new layer is attached to the previous one until the object is complete.”

• Classic or traditional manufacturing is more subtractive than additive. What if the intended patient population is for one person, can a clinical trial be performed for validation? Additive manufacturing poses regulatory and quality challenges.

• FDA has sought input from the medical device industry, manufacturers, healthcare providers and facilities to explore appropriate regulatory approaches for Point-of-Care (PoC) 3D printing of medical devices.

• For example, Mike discusses that the regulation of today was not intended for 3D printing face masks and other protective gear. The lack of regulation should not hold back manufacturers from getting products on the market and through FDA.

• FDA, as well as Mike, recommends software certification for people using 3D printing in a controlled environment to make safe and effective products.

Links:

FDA - 3D Printing of Medical Devices

FDA - Technical Considerations for Additive Manufactured Medical Devices Guidance

FDA’s Role in 3D Printing

FDA - Process of 3D Printing Medical Devices

FDA - 3D Printing Medical Devices at the Point of Care: Discussion Paper

FDA - Classify Your Medical Device

FDA - The 3Rs of 3D Printing: FDA's Role

PART 820 - Quality System Regulation (QSR)

Mike Drues on LinkedIn

Greenlight Guru YouTube Channel

MedTech True Quality Stories Podcast

Greenlight Guru Academy

Greenlight Guru

Memorable quotes from this episode:

“There’s been now about 100, a little more, medical devices that have come through the FDA onto the market that have been 3D printed.” Mike Drues

“The phrase, ‘additive manufacturing,’ comes from the fact that many of these technologies, certainly not all, but many of them are based on layer-by-layer-by-layer technology.” Mike Drues

“Additive manufacturing is 3D printing, but not all 3D printing is additive manufacturing.” Jon Speer

“There’s two ways you can do a validation. One way is to validate the product. The way we do clinical trials today is we essentially validate the product, but the other way we can do a validation is to validate the process.” Mike Drues

“The blending of tech and med device, it’s scary on one hand, but it can be exciting, as well. I’m looking forward to seeing how this impacts and hopefully improves our health care in the world.” Jon Speer

Transcript

Announcer: Welcome to the Global Medical Device Podcast, where today's brightest minds in the medical device industry go to get their most useful and actionable insider knowledge direct from some of the world's leading medical device experts and companies.

Etienne Nichols: Hey, everyone. Welcome back. Today, we're going to be discussing 3D printing. We're going to be talking about the differences in 3D printing and additive manufacturing, as well as some of the FDA's approach to regulating this technology, or should they regulate this technology? If you've listened to the podcast before, I'm sure Mike Drues is a familiar voice. A man who needs no introduction, but Mike Drues, Jon Speer discuss this topic. It's an interesting episode. We hope you enjoy it. If you have any questions or thoughts or feedback, please email us at podcast @ greenlight. guru. We'd love to hear from you. Thanks. Hope you enjoy the show. Hey, everyone. Welcome back to the Global Medical Device Podcast. This is Etienne Nichols, your cohost. With me today is Jon Speer, of course, founder of Greenlight Guru, and also Mike Drues. Today, we're going to be talking about 3D printing, or those of you who are 3D printing experts will get onto me, additive manufacturing and some of the pros and cons, some of the different things that are going on in the industry. So the FDA has... It's not guidance. What would you call it, Mike? There's some FDA comments out there about the additive manufacturing. Some of the questions, and maybe we should just go ahead and ask or start talking about the difference, is additive manufacturing the same as 3D printing? Thoughts, feelings on this. Mike, we'll pass it to you first.

Mike Drues: Sure. Well, Etienne thanks for the introduction and the opportunity to talk about this very important topic. In the interest of full disclosure, I've been working in the general area of 3D printing now for probably 20 years more and there's been now about 100, a little more, medical devices that have come through the FDA onto the market that are 3D printed. So just wanted to share that with our audience, because this is not nearly as far off as some people think. Specifically with regard to your question, Etienne, about additive manufacturing versus 3D printing, look, I don't want to get into semantics here, but from an engineering perspective, 3D printing is a very, very broad category and there are at least a dozen, probably more, different technologies that all fit under the category of 3D printing. Some of them would be considered additive manufacturing. Some of them would not be. So right now, a lot of people, including FDA, are using additive manufacturing, that phrase almost equites or a general sense. I think in the future that's going to become... So I try to refer to 3D printing in general and then a number of these different techniques and here's a little bit of trivia, and then, Jon, feel free to add on if you... The phrase additive manufacturing comes from the fact that many of these technologies, certainly not all, but many of them are based on layer by layer by layer technology. In other words, you put a layer of material down, then you put another layer on top of it. In other words, you add to it. Then you add to that, then you add to that, and so on. So that's where that concept of additive manufacturing comes from. However, as I said, some of the technologies that I work with under the umbrella of 3D printing do not go layer by layer by layer. They're a completely different kind of a technology than that.

Etienne Nichols: One of the things that it almost begs the reality that we are used to subtractive manufacturing. We don't really call it subtractive, but once it becomes as common as subtractive, you're probably right. It'll fall off I would guess. Jon?

Jon Speer: Well, I just want to clarify. So I think what I heard Mike share is true. Additive manufacturing is 3D printing, but not all 3D printing is additive manufacturing.

Mike Drues: Correct, Jon, very well said. Thank you.

Jon Speer: Okay. All right. All right. I guess it might be good to elaborate a bit on that. To Etienne's point, I mean, I think there is actually some guidance from FDA, but it's been a bit, it's a few years old. I see you nodding your head, Mike. Can you remind us a little bit about that, some of the guidance that FDA may have?

Mike Drues: Yeah. So FDA put out the original 3D printing guidance, approximately four or five years ago. We can provide a reference to it as part of the podcast resources. I said at that time, and I say with regard to the more current information that Etienne was referring to today, there's nothing in there that is new in any way, shape, or form.

Jon Speer: Right.

Mike Drues: As a matter of fact, the gist of the guidance from four or five years ago basically said that 3D printing is a manufacturing method and at the end of the day, what it comes down to is not the manufacturing method that you're using, but what it is that you're manufacturing. So one of the examples that I like to use is a knee. If you're 3D printing a knee, then you're still going to have to do all of the testing and so on necessary for any other prosthetic knee. Go and see those guidances, which FDA has put out. There's a bunch of guide knees or hips, or a variety of different medical devices. So there's really not a lot in there that is really new in that regard.

Jon Speer: I guess that makes sense. I mean, to Etienne's point, I mean, I guess the more classic or traditional manufacturing is subtractive in nature rather than additive in nature and I don't think there are too many guidances that we've had from the agency on those sort of manufacturing methods. So that part makes sense, but you talk a knee, a great example, the classic or the traditional manufacturing methodology for a knee implant is generally going to be manufacture these in some sort of bulk, not necessarily one off. I mean, how do you see that as a challenge for that type of product with additive manufacturing? I mean, I make a hundred or a thousand or a million of one size of knee versus making one of one size of a knee. I mean, what are some of the pros and cons that you see with that?

Mike Drues: Well, it does pose some interesting challenges, Jon, both on the regulatory side, which I'm happy to chime in on, and then maybe even on the quality side.

Jon Speer: Sure.

Mike Drues: You can chime in on, but look, if you're making a medical device, regardless of the method, that's going to be used for hundreds or thousands or maybe even millions of your closest friends, then it makes sense to test that on the bench top or in a clinical trial on a few dozen or maybe a few hundred people. But when your intended patient population becomes one person, in other words, we're making one device for one person, or if you want to talk about on the drug side, we're making one drug for one person, and we can do that now as well, FDA approved the first 3D printed drug. I was involved with it about four years ago. So not nearly as far off as some people think. When your intended patient population becomes one person, is it possible to do a clinical trial for an equal one? I believe there's a solution to every problem, including that one and the first step is to get people to think and hopefully to get them to think differently. So as an engineer, Jon, and I would love to hear your thoughts, quality perspective. When I look at a clinical trial, I see nothing more than a validation and for those of you that know something about validations, you know there's two ways that you can do a validation. One way is to validate the product and the way we do clinical trials today is we essentially validate the product, but the other way that we can do a validation is to validate the process. I think that's the solution to the enigma that personalized medicine of 3D printed devices or drugs poses. That is we have to validate the process, not the product because if we insist on people validating the product, like we have virtually all medical devices in the past, Jon, I don't know about you, but this technology's not going to go anywhere. It's just not feasible to do that, but to validate the process, that is feasible, what do you think about that suggestion?

Jon Speer: Well, I think it's good and I think there are even some regulatory precedence for this too. I'm reminded of, and I don't know how popular it is granted, but I believe the FDA digital health, I don't know if it's a division, group, whatever you want to call that, the digital health team at FDA, and the name of their guidance or their methodology is escaping me for a moment, but they introduced this concept of certifying the teams or the process or the methodology rather than the product.

Mike Drues: Correct, for software development.

Jon Speer: For software development, right. So there is some precedence. Granted, it's software and not a tangible good, per se, but you're spot on. I mean, how in the world could I validate the actual product when I've got an N of one and I need to prove the process works, for sure.

Mike Drues: With regard to that certification program that you just referred to Jon, and we've done some podcasts on that topic in the past, maybe we can provide some references, but you may remember that I love that idea. I would love to see that idea applied across the medical device industry broadly, not just for software, but that's a topic of a different discussion.

Jon Speer: Absolutely.

Mike Drues: Coming back to the manufacturing method, Jon, does it make sense for FDA to try to regulate a manufacturing method or a manufacturing technique? Think about it this way. If you're making a catheter, I know, Jon, you come from the catheter world and to a certain extent I do as well. If you're using an extrusion machine or an injection molding machine or whatever to make a catheter or a portion of your catheter, the FDA does not approve that extrusion machine or the injection molding machine. It's indirectly regulated under the quality system regulation and so on, but you don't get a 510K on that machine. You get a 510K on the device coming out of that machine. So why should 3D printing be any different? Some people have asked me," Mike, if we want to develop a 3D printing machine for making medical devices, do we need to get 510K clearance or approval on it?" That still is TBD. It's still sort of a gray area to allow people, but to me it's not a gray area, and in the drug world, it's the same way. FDA does not approve a tableting machine that you make drugs out of. They approve the drug coming out of the tableting machine. So how is 3D printing any different?

Etienne Nichols: The one thing I would have a question about though, is if it is used in a different location, location doesn't matter, I get that, but the people are going to be different using it with a different focus. If you're at a manufacturing facility where you have a conventional way of manufacturing, they're going to be well versed in installation qualification, so forth, IQOPQ. What are your thoughts about that, point of care use, because that seems to be where the benefit of a 3D printed device comes in?

Mike Drues: Indeed. Kudos to you because that's a leading question because that's basically the topic of the last few documents that came out of FDA in this area, and that is point of care, not just regulating 3D printed devices in general, but specifically when they're used at the point of care. Well, my first question is what exactly is that point of care? For example, and I'm going to give you examples of technologies, all of which I either have been or am involved in right now. One of the technologies that I've been involved with for a few years is printing, literally printing a stent, in this particular case, a drug living stent in the cath lab. In other words, not in some distant medical device, manufacturing facility somewhere, but imagine this not so hypothetical scenario. You're doing a cardiac catheterization. The cardiologist makes some measurements of that particular patient's anatomy, the diameter, the length, the geometry, the tortuosity, and so on. He or she takes that information, feeds them into the 3D printing machine, which, oh, by the way, is in the same room or maybe at least in the same building. That stent is printed right there and then it's taken out of that machine and, boom, seconds or minutes later, it's put into that patient. So that's one example of point of care. Here's another example of point of care. I mentioned earlier printing drugs. Well, why when you get sick and you go to the doctor, do you take a script to the CVS or the Walgreens and they take some pills out of the bottle and give them to you? We've been doing that for hundreds of years, but it makes no sense. So imagine that script, instead of going to Walmart, that information is sent to a 3D printing like machine in the back of the physician's office and those pills are printed exactly for you, Etienne, not Jon or me or anybody else. Further, not just the drug, but a combination of drugs at the dose that you need, at the kinetics that you need, and so on. There's another example of point of care. Then my third example that I'll share with you and perhaps my favorite, because it's potentially the most concerning or potentially problematic is what about having a 3D printer device that you can print medical devices in your own home, in your kitchen or in your garage or in your basement? We now have, and some of this is floating around on the internet, people, including even high school kids and college kids who are printing prosthetics, who are printing braces, and so on, and so on. There was an example on CNN that I use in some of my presentations where a high school kid printed braces for himself for about 60 bucks instead of several thousand dollars for a conventional set of braces. So what does even point of care mean? In those kinds of scenarios, especially in the home, is it even possible for FDA to regulate something like that? What do you think of that?

Etienne Nichols: It's challenging because you're absolutely right. The definition of point of care, right now, I usually think of right there, and well, kind of like what you're saying with the drug alluding stent, which blows my mind a little bit, considering that that's a combination product. So you have a lot of different.

Mike Drues: Fair enough. It's a combo product. You are correct.

Etienne Nichols: It's exciting that sort of thing is going on, but I totally agree, and your third point, especially. When you only have an N of one, in my mind, inspection becomes more important and you don't even have an inspector in that case. I don't know. What are your thoughts, Jon?

Jon Speer: I don't know. The human in me or I guess the potential consumer of healthcare at some point in time in my life, or certainly loved ones who are consuming or have the need for procedures and whatever the case may be, there's something about that that's kind of appealing. I mean, confession, I don't really like to go to the doctor. I suspect few people do. Not that I avoid it at all costs, but I don't go all that often, but how convenient would it be? Part of me has been thrilled by some of the things that have been happening with healthcare. I'm not going to call them innovations because I don't think they are, but movements in healthcare since the pandemic. I mean, being able to, like we're talking on Zoom today, we're all in three different locations across the country. I'm going to be way more interested in having a doctor appointment if I can interact in a way that's less interrupting to my life versus the alternative. By the same token, if I needed a relatively benign procedure or medical device in some way, wow, how cool would it be to be able to click print and here it comes? Out of my 3D printer comes my braces or whatever the case may be. So part of it's kind of interesting from that perspective, but the other side is also interesting. I mean, Mike, I think you asked a question or something along these lines of what role does FDA or should FDA play? I mean, they're still medical devices, but if I, as a person who designs and prints my own medical devices uses on me and only me, should FDA weigh in on that? I guess, technically speaking...

Mike Drues: What if...

Jon Speer: Yeah, go ahead.

Mike Drues: What if it's not just you, Jon?

Jon Speer: Yeah.

Mike Drues: What if I print braces and give them to you? Here's another interesting regulatory challenge, if you will, that personalized medicine, including 3D printing technology poses. A lot of what we're talking about today are just demonstrations of how it's a challenge to bring truly revolutionary products and technologies to the market, through a regulatory system that, let's be honest was never in a million years...

Jon Speer: Yeah.

Mike Drues: The current regulatory environment was built on the me too model, on the blockbuster model. You make one device or one pill for millions and millions of people, but here's the next regulatory challenge that I wanted to bring up. As you guys know, FDA does not regulate the practice of medicine. So when a physician does something, then FDA has absolutely nothing to do with it. That's the practice of medicine. The only thing that FDA can do is regulate us, meaning industry. That's not true just for physicians literally practicing medicine, but one could make the argument about a pharmacist. When they're compounding drugs in the back of a pharmacy, how is the 3D printing of the drug any different than pharmaceutical compounding today, which FDA does not regulate? How is it any different than the reprocessing of medical devices, which historically FDA has not regulated, although now they're trying to, because of the UCLA disaster with the duodenoscopes that you and I talked about in the past, Jon, and so on and so on. So here's a couple more specific examples. I remember almost 30 years ago when I started working in cardiology, it was not uncommon for a physician to take a catheter out of a box before they put it into the patient. They didn't like the shape of the catheter. So if, I don't know if you saw this before, Jon, they always had a teapot going in the back of the cath lab and with water boiling. I always thought, gee, maybe somebody wants to have some tea. Well, it's not because they want tea. It's because they would hold the catheter over the steam and use that to bend the catheter.

Jon Speer: Shape it, yeah.

Mike Drues: To shape it, to get it into the shape. This was common practice for a very, very long time.

Jon Speer: Yeah.

Mike Drues: During COVID, I mean, how many people, I know you and I both, Jon, know examples where physicians and other people were printing masks and face shields and other kinds of protective devices. Did FDA have anything to do with that? No, largely because it was the practice of medicine. So I think that one of the big challenges that we're facing is that the regulation that we have today was not intended for this. So there's two solutions to that. First is we've got to fix the regulation that we do have, and that's taking a very, very long time. It's happening, but I mean, that 3D printing guidance, when it came out of FDA that I referred to a few minutes ago, it came out about four or maybe five years ago. At that time I said publicly," Kudos to FDA for putting it out," but I said," Shame on you because that should have been out at least a decade before, if not more than that. It's really holding us back." But the other thing that I work with companies all the time is, as you know, Jon, I refuse to let regulation, or in this case, the lack of regulation, hold me back. We've got to figure out a way to get these products onto the market and through the FDA, given the limitations of the regulatory environment that we have, given the quality challenges that we have today as well. These are the things. So I want to try to keep this discussion on the positive side and figure out ways that we can make these things work as opposed to on the negative side. Quite frankly, just bitching and moaning and groaning about all the reasons why we can't make something happen, because we've got way too many people in this industry that are quite good at that.

Jon Speer: Yeah, and just the whole technology of 3D printing, I mean, Etienne, no disrespect, but you probably don't remember working before 3D printing.

Etienne Nichols: I had to learn it in college. You're absolutely right.

Jon Speer: But I remember very distinctly, very vividly the first product that I worked on and developed where we actually incorporated 3D printing, and that was probably back in, let's go with 2000, somewhere around then. The use of 3D prototyping at least then was primarily a predominantly for prototyping purposes, not necessarily for finished product purposes, but here today in 2022, I mean 3D printing, Mike has shared his experience with 3D printing pharmaceuticals and drug alluding stents. I mean there's 3D printing knee implants and other orthopedics and a litany of other products. So obviously the technology has a lot of applications and it's exciting to see how that's been adapted to a manufacturing methodology.

Mike Drues: Well, let's take one application, Jon, that's been around for a very, very long. That is anatomical models.

Jon Speer: Yeah.

Mike Drues: So I'm going to give you a few scenarios and you tell me what, if any, FDA involvement has in this. If I have an anatomical model, let's say, produced, let's say not by 3D printing, but by some conventional molding technique and I use that model in medical school, for example, to train on anatomy, does FDA have anything to do with that?

Jon Speer: My gut says no.

Mike Drues: No, and what's the reason why? Because it's the practice of medicine.

Jon Speer: Right.

Mike Drues: In this case, it's training. FDA has nothing to do with that. Well, let's now take the step further. Let's say that we 3D print that model, but it's still used for educational purposes. So we've changed the manufacturing method, but not the intended use. Does FDA have anything to do with that?

Jon Speer: Still say no.

Mike Drues: No. Now let's say we print that anatomical model, but we, instead of taking some generic Gray's Anatomy like information to print a model, we take information from a specific patient. In other words, from a CT or an MRI or something like that and we print that model that corresponds to, say, your anatomy, Jon, but we don't use it for teaching purposes in medical school. We use it for surgical planning. In other words, prior to the surgeon opening you up, you said earlier, Jon, you don't go to the doctor very often, but let's say that you did God forbid go to the doctor and they needed to open you up. So before opening you up, they would print this model and they would figure out what the appropriate course of action would be. Would FDA have anything to do with that?

Jon Speer: Still going to say no.

Mike Drues: Still going to say no for the same reason.

Jon Speer: Yeah.

Mike Drues: Because it's the practice of medicine. Now let's take it a little bit further. Now let's say we print that model, but now we're going to use it, for example, as part of our bench top testing so that if you're developing a catheter or a stent or a heart valve and you want to test it on the bench top, and maybe you're going to use some of that data as part of your regulatory submission, does FDA regulate that?

Jon Speer: I'm going to say no with a caveat. No, but I still need to demonstrate that that model is applicable and appropriate for the product that I'm developing.

Mike Drues: Correct, Jon, so I think you're four for four. So the answer is...

Jon Speer: Yes.

Mike Drues: No, they don't regulate it directly for the same reasons that I said earlier. FDA does not regulate directly, anyway, your injection molding machine. You don't get a 510K clearance on your molding machine. You don't get a 510K clearance on your anatomical model either, although perhaps you should, but that's the topic of a different discussion, but the underlying reason is exactly the same.

Jon Speer: Yeah.

Mike Drues: It's that FDA doesn't regulate the practice of medicine. So it's not the machine that's producing the product. It's the product that's coming out of the machine that's the most important thing.

Jon Speer: Can I ask a twist on that though? So yeah, another example. So let's imagine that I am a stent graft manufacturer to treat aortic aneurysms.

Mike Drues: Triple As. Yeah.

Jon Speer: Triple As, and I'm able to print a patient specific anatomy of their aneurysm and I use that as a guide or a template, if you will, for me to manufacture that patient specific stent, what are your thoughts about that?

Mike Drues: Well, look at the end of the day, let me be crystal clear on this, there's a difference here between looking at this from a regulatory perspective, in terms of what is required versus the broader what is the right thing to do perspective.

Jon Speer: Yeah.

Mike Drues: I want to be absolutely crystal clear here. I'm not, as I never have before, Jon, been an advocate of taking short. We're going to be printing a trip away stent graft or anything else. At the end of the day, whether this goes through the FDA or not, I could care less. What's most important is that you do all of the testing and so on to make sure that the product is safe and effective, that it's biocompatible and all those other kind of things. So to me, as a professional biomedical engineer, that goes without saying.

Jon Speer: Yeah.

Mike Drues: But from a regulatory perspective, one could make the argument that if a physician was doing this, him or herself, in other words, if he or she had the capabilities in their own lab to make this for one particular patient, then they would not need to go through FDA. I'm not suggesting that I agree with that. I'm just saying that one could make that argument, and this is one of the reasons why, Jon, from a regulatory perspective, I think that the CDE, the custom device exemption, although it's not a perfect regulatory pathway to market for personalized medicine, in my opinion, I think it's an appropriate pathway to market for personalized medicine in spite of the fact that FDA made it very clear in their guidance from about four years ago, 3D printing guidance, that the CDE should not be used for 3D devices like this. I strongly disagree.

Jon Speer: Yeah.

Mike Drues: I think that the CDE is the best thing, the pathway that we have right now. It is not a perfect pathway and I think that we definitely need a new pathway specifically for personalized medicine, not just of medical devices, but of drug, because I see a lot of the changes to be similar, and we have to be fair. We've had discussions at FDA about that, but it's taking a very, very long time, a very long time.

Jon Speer: Yeah.

Mike Drues: I don't know about the other folks in this audience, but I can't say to one of my customers," I would love to help you bring your new really cool product, or coming from Boston, wicked cool product onto the market, but we're going to have to wait 10 years for FDA to get their ducks in a row to create a new pathway to do that." That's just not going to cut it.

Jon Speer: Yeah. These are class two these days aren't they?

Mike Drues: Most of them are, correct, yes.

Jon Speer: 510K? Yeah.

Mike Drues: Right, and when we did bring the first 3D printed knee onto the market, Jon, a few years ago, and I was one of the principal architects of the regulatory strategy on it, we did it as a 510K.

Jon Speer: Yeah.

Mike Drues: We did not do it and we certainly did not do it as a PMA. We did it as a 510K.

Jon Speer: The predicate was a standard knee?

Mike Drues: Basically.

Jon Speer: Yeah. Basically.

Mike Drues: What we had to do was we had to argue that the manufacturing method was different. There's no question about that, but at the end of the day, we had to show that the knee coming out of our 3D printing system was essentially the same.

Jon Speer: Substantially equivalent.

Mike Drues: Substantially equivalent as the knee coming off of our conventional manufacturing system. At a very, very high level, that was the regulatory lodge. We further, to meet the 510K requirements, we had to show that there were no new questions of safety and efficacy, and we had to show that there were no changes in overall risk. So all of those regulatory requirements are exactly the same, but I'm curious, Jon, because you're probably more knowledgeable about the world than anybody I know. What do you think when it comes to 3D printing, especially point of care, that Etienne asked us to focus on at the beginning here, what are the challenges of verification and validation? What are the challenges of product consistency or process consistency when we're making, instead of hundreds or thousands of devices at a time, we're making one device at a time, and especially if we're not doing it in a conventional medical device facility, in a manufacturing facility, but instead we're literally doing it in the hospital, maybe even at the patient point of the... What do you think about that, Jon?

Jon Speer: Well, I think Etienne highlighted a key point. I think those types of scenarios put more emphasis on the inspection methods that one uses to make sure that the product that was produced from the 3D manufacturing methodology, in fact, meet the specifications and criteria that were defined. Now, even with that said, I mean, some of these point of care facilities, I mean, they are not accustomed nor do they have the necessary infrastructure or processes or resources to act as a manufacturer, but there are different responsibility. I mean, just think GMP, good manufacturing practices, there's elements of GMPs that are certainly going to apply in this case. That is making sure that product that you designed, put through the 3D manufacturing methodology, that the product that results from that meets those predefined specifications. So I think it's possible. I just don't know a lot of point of care facilities that are set up to be a manufacturer.

Mike Drues: Well, let's take that, what you just called predefined specifications, a step further, Jon.

Jon Speer: Okay.

Mike Drues: My question is what specs and who sets them? In other words, while you're laughing, let me take this a little further to illustrate.

Jon Speer: Yeah, I know. That's a good question.

Mike Drues: So in a traditional medical device company, the company sets the specs. In other words, if I'm printing a knee, a catheter, I don't care, whatever it is, the company sets the specs. Part of the regulatory process is to take those specs to the FDA and vet them with the FDA. In other words, they say that, okay, we make a device that fits these specs.

Jon Speer: Right.

Mike Drues: If it fits these specs, it will be safe and effective. It will do the things on the label and yada, yada, yada, but with personalized medicine, now the physician sets the specs. In other words, the physician looks at the patient, their anatomy, their physiology, maybe even their molecular biology. They enter those specs into the machine and the machine will produce the device according to the physician set specs, not the company and FDA vetted specs. Does that change the calculus at all here?

Jon Speer: I don't think so. I mean, granted, the physician may not be used to QSR and 820 and design controls and the contents of a regulatory...

Mike Drues: I'm sure they probably haven't heard any of those things before, Jon.

Jon Speer: No, that's true. They probably haven't. I mean, I've worked with plenty of physicians over the years who built the prototype, a crude one, but nonetheless a prototype and they struggle to understand how they could not go to market with that prototype.

Mike Drues: This is the point that why I'm bringing it up. This is exactly why I'm bringing this up. Here's the solution, or at least this is Mike's solution to this problem. When it comes to personalized medicine, the burden, if you will, the regulatory or even the quality burden is not to make sure that the specs are correct because those specs are being set by the physician or the user or the maybe in some cases, even the patient. The burden is to make sure that, regardless of what the specs are, when they're put into the machine by whoever puts them in that what pops out of the machine at the other end fits those specs.

Jon Speer: Correct.

Mike Drues: Whether it's right or wrong, I hate to say it, but that's somebody else's problem, but we need to make sure that the machine is capable of making a product that will fit the specs. So if I say that the machine is going to make something that's got dimensions of X, Y, and Z, that we need to make sure that the device coming out of it fits that X, Y, and Z dimensions, plus or minus a little, whatever it is. It's not the question of are the dimensions X, Y, and Z, correct. That's a completely different discussion. This probably sounds reminiscent to you, Jon, in the design control discussions that we've had. Have we designed the device right? Have we designed the right device? This is just sort of a riff on that. Do we meet the specs or are the specs correct? They're two different questions. Go ahead, I'm sorry.

Jon Speer: But you're not implying that if I'm a medical device, let's just say a traditional medical device company. I'm registered with the FDA as such and I design a device that can be 3D printed and I get the necessary regulatory clearances or approvals, whatever the case may be for that product. You're not implying that I am held to a different standard or set of rules, if you will, versus a point of care facility that's doing the exact same thing, but has never operated as a medical device company, are you? You're not implying that there's different rules?

Mike Drues: Philosophically, no, but realistically, probably yes.

Jon Speer: Yeah.

Mike Drues: Because the medical device company is subject to all of that rules and regulation and the FDA oversight, or what I like to call the sanity check, but when, not if, when these things are being done at the point of care, and remember, as I talked about earlier, point of care doesn't have to be in a hospital.

Jon Speer: Right.

Mike Drues: It could be your kitchen. It could be in your kitchen. Is that even logistically possible? One of the suggestions that FDA does make in the new documentation, and it's a suggestion that I've, in the past, it's a riff on what you referred to earlier, Jon, the software certification program, is for people that are actually running or controlling these 3D printing devices, that some sort of license or certification for people using that equipment is a good idea. I personally think that's a good idea. That's a step in the direction. Just like if you want to drive a car, you need to have a license. You need to demonstrate some competence. Just like if you want to perform surgery, you need to have graduated from medical school and so on. So having some sort of a certification there, I think is a good idea for people that are doing this in a controlled environment where your point of care is a facility, but how is that even enforceable when we get to the high school kid, that's printing braces in the garage? Take it just one step further, Jon, from a business perspective, I think that this kind of technology has the potential to really shake things up in the medical device industry. Think about it this way, Jon, most medical device companies, they're used to thinking of their revenue, the amount of money that they make as a function of the number of devices they set.

Jon Speer: Yeah, exactly.

Mike Drues: Well, once people start to print their own device, how many devices are the conventional medical device companies going to be selling?

Jon Speer: Oh, wow.

Mike Drues: Something to be thinking about.

Etienne Nichols: It just made me think of the SAAS model actually. So it software as a service. So if you had a company that maybe they have a certain model that you could license and it changes, and let me go upstream because I want to ask a question. So when you're talking about that knee implant that maybe is being 3D printed, I'm not sure in your instance where it's being 3D printed, but to Jon's point, when you have that being 3D printed, where is the burden of responsibility for that device? Is it the medical device manufacturer or is it the person printing it? There's a certain amount of testing that went into the design of that, that maybe the doctor or clinician is not going to be privy to, maybe the fill structure or the geometry of the interior of that. Maybe it's a homogenous device. Maybe not. They're not going to care about that. There's certain parameters they do. What are your thoughts, I don't know, on the shared or duality sharedness?

Jon Speer: Well, before Mike answers, let me add another twist to your question, Etienne. What if I, as a doctor, maybe I didn't design the knee implant, but maybe I was able to get my hands on some CAD models of existing knee implants, or maybe I have some.

Mike Drues: Which by the way, are floating around on the internet somewhere.

Jon Speer: Floating around the internet or I could use...

Mike Drues: Just like that.

Jon Speer: A scan of something. Yeah. Go ahead.

Mike Drues: Just like 3D printing of schematics for printing a gun.

Jon Speer: Yeah.

Mike Drues: Which was in the story about the TSA a few years ago, but anyway. Purely hypothetical, Jon. Could never happen in reality, but anyway, go ahead. Continue with your example.

Jon Speer: I was just going to say that that was the twist, Etienne's, where's the burden of proof or responsibility lie?

Mike Drues: So, great question. So let's just use the knee example as a way to peel back this onion a little bit, because I think even though, as I said, at the beginning, we have now more than 100 devices that are through the FDA and are on market that are 3D printed, most of them. I've had my fingers in many of them, certainly not all. Most of them are pretty, let me just say from a biomedical engineering perspective, they don't very excite me very much, but 3D printing a knee, an implantable device, that is something that's very significant and we don't have too many of those yet. This was among the very first. First of all, to your questions, Etienne, we're not doing that at the patient's bedside, at least not yet. That's still being done in the medical device company's facility, although I don't think, as I talked about before, that's the future of the technology, but that's what we're doing right now. More importantly, to address the whole question you're raising about the specifications and how do we know if X are right and so on, my advice to the company at the beginning, this is exactly what we did, although they didn't want to do it at first, is limit your 3D printing of the knees, at least at the beginning, to make knees that correspond to 3D printed needs that are already commercially available. In other words, eyes, the shape, the geometry, as much as possible, the mechanical properties, the hardness derometer, compression strength, and all that kind of stuff. I'm just curious to put you on the spot here a little bit. Why do you think that was my advice to the company, because that's not what they wanted to do initially, but that's what they did at the beginning, why do you think that was?

Etienne Nichols: So you're saying they were designing ones that are equivalent, not just a 3D printed, but ones that are not necessarily one offs?

Mike Drues: The ones that were already on the market. In other words, we purposely designed these things to be as close as we could to devices that already exist in terms of size and shape and everything else.

Etienne Nichols: I assume to compare whether it's adverse event, complaints, and failures?

Jon Speer: Well, and I would say the predicate model is probably a little bit more straightforward in the eyes of FDA if you choose shapes and sizes that are already preexisting.

Mike Drues: That's exactly correct. So here's the regulatory logic. So if I can show that my device coming off of the 3D printing machine is basically the same, IE, substantially equivalent as a device, a knee that's already on the market, if I can show that, and I'm not going to get into the detail here of how we did it, some of it is still very confidential, but if I can show that, then essentially, I can totally remove the knee from the equation. In other words, I don't have to say anything about the knee.

Jon Speer: Yeah.

Mike Drues: All I have to do is validate, if you will, the 3D printing process, which is, oh, by the way, the solution to the enigma that I posed earlier about 3D printing and that is validate the process, not the product. Then the next step, and I have to be careful what I say here, because some of this is still unfolding as we speak, the next step would be to go back to the FDA as a label expansion and say," Okay, now I'm going to start relaxing my criteria," and I'm going to say," Okay, now the physician," remember before at FDA, we said they can only print knees of this size. Now I'm going to say," The physician can print any size that they want as long as it's between X and Y," and where do those numbers X and Y come from? Do I pluck them out of the sky? Absolutely not. They correspond to the minimum and maximum size of the knees that are commercially available. We do a label expansion that way and then we go back there with a third label expansion and say," Now we can place any size that we want." So this is the best way. It's certainly not a perfect way, but it's the best way that I've been able to come up with to be able to take truly revolutionary, I'm not talking about evolutionary technologies here, but revolutionary technologies and bring them through a regulatory environment onto the market that it was clearly not intended to support. But as I said earlier, and I believe this strongly, we cannot use regulation as an excuse to hold us back. We have too many people in this industry who seem to say that, oh, I have this wonderful idea for the greatest thing since sliced bread, but I can't do it for all of these reasons that FDA is preventing me. I'm sorry, that kind of thinking drives me nuts.

Etienne Nichols: I'll just say one thing, because you alluded to the people who just complain about this type of thing or the complaint. It's really exciting to see, and there are a lot of applications that it's going to a lot. My wife was a nurse Malawi for a while and she said there was one hospital with a heart doctor and they lacked a lot of equipment. This is the kind of thing that could provide that kind of equipment in places where they might not otherwise receive it. So it is exciting technology and I'm glad there's people like you working on working out the kinks.

Mike Drues: There are a few, there are not enough. There are a few. Thank you.

Etienne Nichols: Any thoughts, Jon?

Jon Speer: Just looking over some of the notes that I had ahead of time. I think we hit most of the things I wanted to talk about. Some of the other things may be rabbit holes, but I think it's really going to be... I guess I could sum it up as this. I'm excited about the potential and the possibilities that additive manufacturing and 3D printing. I like Mike's mantra as per usual. To paraphrase, don't let the regulations get in the way, just figure out a path. Also to quote something that Mike will say from time to time is lead don't follow, and I think this is an opportunity that if you have a technology where you could do this and it makes sense, lead. Build a strategy, reach out to a guy like Mike Drues who has a lot of experience with these sort of things. I'm, for one, kind of excited about this. Many of you have probably heard me talk about the blending of tech and med device. It's scary on one hand, but it can be exciting as well, you know? So I'm looking forward to seeing how this impacts and hopefully improves our healthcare in the world.

Mike Drues: At the end of the day. I'm glad you picked up on one of my messages, Jon, and that is don't let the regulation hold you back, but I also want to make clear that statement is not underlying not substantially equivalent to don't follow the regulations.

Jon Speer: Right. Don't ignore.

Mike Drues: Don't ignore the regulation, but understand the regulatory logic, not necessarily the literal interpretation of the law, but the regulatory logic so that you can apply it to technologies like 3D printing or other technologies that don't easily fit into the existing structure that we've been using in the past. But at the end of the day, as long as it makes sense from a biology and engineering perspective, what you're doing, whether it's 3D printing or anything else, that should be what's most important.

Jon Speer: Yeah.

Mike Drues: I'm not advocating taking shortcuts.

Jon Speer: For sure.

Mike Drues: I'm certainly not advocating not doing testing or bringing products onto the market that are not tested enough or unsafe, but on the other hand, we've got to be able to do it in a fairly timely way so we're not spending decades and decades to do a seemingly simple thing.

Jon Speer: Yeah, and to hopefully state the obvious after that, the goal, the objective as medical device professional or a healthcare professional who may be making your own devices is still to make safe and effective products, right?

Mike Drues: Absolutely.

Jon Speer: Even if maybe you only need one device for that patient specific application, maybe you need to make two, and one of those is a model that you're using to do all of your performance testing and all that. Whatever the case may be, but be smart about it. Make sure that at the end of the day, it's safe and effective because...

Mike Drues: I know we got to wrap this up, Etienne.

Jon Speer: Yeah.

Mike Drues: I know that you're going to end this, but if it's okay with you, I'd like to put our newbie on the spot here for just a moment, Jon, and when you wrap this up, Etienne, Jon, you and I, when we end our podcast, we both usually like to share what are two lessons to be learned. So, Etienne, you're now playing in the big league. You're sharing the stage with Jon and I. So as you've listened to our conversation about 3D printing, what do you think are the couple things that were most important for audience to come away with? We can use that as our conclusion for today's podcast discussion. Etienne, take it from here.

Etienne Nichols: Sure. All right, I'll see what I can do here. So one of the things that stood out to me obviously is the definition of point of care, understanding that, and really, I suppose if I were to sum that up is understanding the letter of the law and understand the spirit of the law and see how those intersect. Maybe the letter of the law potentially needs to change, but I definitely agree with that. Taking a risk based approach for every device and following those regulations, that's going to be key. If I go back to the very beginning, the definition of 3D printing, the pros and cons and the definitions of what those are, I think that's very important takeaway, but following the regulations and the spirit. What have I missed though? Any thoughts?

Mike Drues: No, it was not meant to be a test. I was really trying to measure the efficacy of Jon and my communication method.

Etienne Nichols: Yeah.

Mike Drues: By seeing what you came away with, because at the end of the day, Etienne, that's what's most important. So I think you did a nice job. My intention here was not to grade you in anyway.

Etienne Nichols: Well, I appreciate it. It was enlightening for me and I enjoyed the conversation. I guess we'll end it there. I'm looking forward to our next conversation, but for those of you who've been listening, you've been listening to the Global Medical Device Podcast. You won't be graded either just yet, but eventually it's possible, so stay sharp and stay tuned. We'll see you next time. Thanks, everybody.

About the Global Medical Device Podcast:

The Global Medical Device Podcast powered by Greenlight Guru is where today's brightest minds in the medical device industry go to get their most useful and actionable insider knowledge, direct from some of the world's leading medical device experts and companies.

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