By Michael Drues, Ph.D., President, Vascular Sciences
3D printing has taken the medical device industry by storm in recent years, initially as a prototyping tool, but increasingly as a method for producing finished devices. In fact, some 85 3D-printed devices already have been brought to market in the United States, and that number is growing rapidly. Nowhere is this trend more evident than in the area of personalized medicine, where individualized devices can be manufactured on demand, custom-fit to the needs and anatomies of specific patients.
Yet, despite 3D printing’s continued growth in the industry, the regulatory pathway to market for 3D-printed devices remains murky at best. Here, we’ll examine how best to navigate a U.S. regulatory system that is not designed for these revolutionary technologies.
3D printing is an example of personalized medicine, i.e., making a device (or a drug, for that matter) specifically designed for one patient, as opposed to the traditional one-size-fits-all or blockbuster approach that we have used in the past. Clearly, our existing regulatory framework was not designed for the personalized approach.
Consider this: When our intended patient population for a new medical device is thousands (or perhaps even more), it makes sense to do a clinical trial on a few dozen patients to make sure the product is safe and effective. But when our intended patient population is only one person — as is the case with personalized medicine — is it even possible to conduct a clinical trial ? I believe there is a solution to every problem, including this one, and the first step is to think differently!
As an engineer, when I look at a clinical trial, I see nothing more than a validation. And a validation can be done in one of two ways. We can validate the product — and the way we have done clinical trials in the past is essentially a product validation — or we can validate the process. The solution to the clinical trial enigma in personalized medicine is to validate the process.
So we need a new pathway to market for such products, both for medical devices and for drugs. To be fair, there are ongoing discussions at FDA regarding a new regulatory pathway for personalized products like 3D-printed medical devices, but it’s taking a long time.
Still, 3D-printed medical devices are getting through FDA and onto the U.S. market. Most of them are 510(k)s, some of them are premarket approvals (PMAs), and they cover a broad spectrum in terms of device technologies. Each 3D-printed device presents its own set of regulatory challenges, from relatively simple devices, like surgical instruments and prosthetic limbs, to permanent implants, like total knee replacements.
And things will just get more complicated as the technology is further developed. Clearly, the future is in more sophisticated products than can be 3D-printed currently, like combination products and, eventually, living human tissue for use in drug screening and organ replacement, to name just two!
3D-Printed Artificial Knee Example: How To Apply Regulatory Logic
This is one of several products that I’ve had my hand in recently. A knee replacement is a permanent implant, so defined by regulators because it is indicated to stay in the body beyond 29 days. Knee implants, like most orthopedic implants, can be brought to market under the 510(k), essentially because they were on the market prior to 1976 and they were grandfathered in. So, is the 510(k) pathway right for bringing a 3D-printed knee onto the market? I have mixed emotions on this.
On one hand, I don’t think the conventional pathways to market — 510(k), PMA, de novo, human device exceptions (HDEs), custom device exceptions (CDEs), and so on — are the appropriate pathways for personalized medicine. On the other hand, we don’t want to wait years for FDA to create a more appropriate pathway to market. So the question becomes, how can we bring that 3D-printed implant market today, ideally under the 510(k)? The answer: Apply regulatory logic.
Regulatory logic is important because there is little actual regulation concerning 3D printing and other personalized medicine. Not-so-hypothetically speaking, if I can show that a 3D-printed knee is substantially equivalent to a knee produced by a traditional manufacturing process, then I can remove the knee itself from the regulatory equation — all that remains is to validate the 3D printing process. That’s the crux of being able to bring a 3D-printed device onto the market under the 510(k).
Furthermore, I can mitigate my regulatory risk — the probability that I will not be successful in selling my regulatory strategy to the FDA — by limiting my 3D-printed knees to sizes already available, off the shelf, via traditional manufacturing processes.
Later, I can do a label expansion to add additional sizes outside the original sizing range and, eventually, any customized size. I ultimately want to enable surgeons to make the best choices for their patients, based on each patient’s anatomy and physiology. However, at least initially, introducing new sizes is more of a challenge from a regulatory perspective. This same logic is applicable to other, if not all, medical devices.
By example, if not by definition, regulatory 101 says that label expansions are easier to do than bringing a new product onto the market. It’s a strategy often used in the drug world, and one that we could use a lot more in the medical device world. It can help medical device companies reliably get their devices to market by opting for a series of well-planned, well-executed baby steps, rather than one great big step.
This is a great example of how we can use regulatory logic to accomplish what we want to do, as opposed to following regulation. From a regulatory perspective, that’s an advantage, because it lowers our regulatory burden and equally, if not more importantly, it lowers our regulatory risk.
What Can We Learn From The First 3D-Printed Drug?
FDA recently approved the first 3D-printed drug, Spritam, which is designed to reduce seizures among epileptics. On the surface, it would seem like 3D printing a drug is very different from 3D printing a medical device, but the regulatory logic is exactly the same.
Mirroring the 3D-printed knee example we discussed earlier, if we can show that the drug is the same in both the traditionally manufactured pill and the 3D-printed pill, we can remove the drug itself from the equation — all that remains is to validate the 3D printing process.
Just like with the knee, we can further mitigate our regulatory burden by choosing an existing drug, as opposed to a new drug, and by limiting the dosage to what’s already commercially available. Through later label expansions — and this is where the real power of 3D printing or personalized medicine comes in — we can modify the dosage and kinetics (release rates of the drug) of the pill, and eventually introduce different combinations of the existing drugs or brand new drugs into these 3D-printed pills.
This example, too, illustrates the power of regulatory logic and emphasizes the risk mitigation strategy. This is one of the reasons why I say that, although I believe we need a new pathway to market for personalized medicine, I do not believe that we need different pathways to market for personalized medical devices and personalized pharmaceuticals. I think that if we approach it the correct way, the same pathway can be appropriate for both.
FDA Guidance On The Way?
FDA is making progress. Last October, FDA held a two-day public workshop on 3D printing, and there was a lot of discussion by a number of experts. But, since then, very little has been officially released. As a matter of fact, FDA has had technical guidance for 3D printing on its list of priorities throughout fiscal year 2015.
In my opinion, we should have that guidance already — years ago, in fact. Its delayed release has held back medtech, since the majority of medical device companies do not want to be the first through the door at FDA with a new technology, whether it’s 3D printing or something else. They would rather wait for others to do it first. They would rather wait for FDA to put out regulation and guidance on it.
I understand that, but if everybody felt that way, we’d still be living in caves. Don’t wait for anybody, including FDA, to tell you what to do. Figure out what you think is necessary, from an engineering perspective and from a medical perspective, and then go work with FDA to make it happen. Somebody has to be first.
Work With FDA, And Explore Every Regulatory Option
There’s no bigger fan of communication with FDA than I am. When seeking FDA approval of revolutionary technologies, 3D-printed or otherwise, communicate early and communicate often. But there’s a caveat: Lead, don’t follow; tell, don’t ask. It’s not their job to tell you, and you’re opening up a Pandora’s Box if you ask an open-ended question. It’s your job to figure out what to do: Come up with a plan that makes sense from an engineering perspective and from a biology perspective, and then go to FDA to sell it.
I think there are too many people in our industry who blame the FDA when our medical devices fail to make it to market. The FDA has an important job to do, and we need to work together with them to get the best products — the best technologies — on the market to benefit the people we’re trying to help.
Finally, take baby steps, using label expansion to your advantage. You might come out with a device that doesn’t have quite as many bells and whistles on it as it could, but once that device is on the market, through a series of label expansions, you can add more things to it later.
Taking this approach, you can always discover at least one — and, usually, more than one — way to get your revolutionary product to market.
Michael Drues can be contacted via email or LinkedIn.