This 19-minute compilation from 2014’s 10x Medical Device Conference features Ed Black, Tom KraMer, Pat Kullmann, Doug Limbach, and Bruce MacFarlane on the tricky path for device innovation.

On one hand, you want to be THE SAME.

• If you’re substantially equivalent to an existing device, you get to save on clinical trials.
• And you likely shorten the time for FDA clearance. On the other hand, you want to be DIFFERENT.
• If you’re materially the same as an existing device, why should CMS give you a reimbursement code?
• If you’re materially the same, do you deserve a patent?

Ed Black: A couple of things about reimbursement fundamentals as you go through your own planning. We always talk about kind of the three essential barriers you have to figure out.

There’s coding, whether or not there’s a healthcare kind of procedure code that really describes a service or the manner in which physicians would use it.

Coverage is that question of whether or not Medicare and third-party payors will cover procedures your devices permit and if so under clinical circumstances.

And on payment, are physicians and hospitals going to be paid enough to encourage product adoption without being too expensive, thereby discouraging government and private insurers from covering it?

And in a reimbursement assessment, I think anyone will say these are the three baselines you really need to account for in your planning.

It was the chief medical officer from UnitedHealth Group headquartered here in Minneapolis speaking to our LifeScience Alley Annual Meeting and Expo three years ago, but he got up in front of 1500 med tech executives who are kind of used to getting this nice rah-rah speech for an opening comment at their big annual meeting.

He came up there and he told these people, “You can’t be seduced by all the wonderful technology, toys and other stuff, because every idea ain’t good. And at the end of the day you have to ask yourself, does the technology work? Will it improve quality, help manage costs, be good for the consumer, and meet a real need?”

He kind of stunned the whole audience of 1500 of people who just love their technology, have invested hundreds of thousands if not millions of dollars in it, and all of a sudden were kind of hit with this like, “Yeah, you’ve got all this stuff but we don’t need them, we don’t want all of it, and you’re going to have to figure out how you’re going to sell it to me so we covered for our multimillion dollars worth of members.

And don’t bring me technology that is comparable to what exists out there today and expect me and my staff to go through all this policy review time, figure out whether we should cover this new technology, which is so similar to everything else that’s out there in the marketplace and doesn’t meet a real consumer need, doesn’t help me manage cost because you said your big problem in this country is managing healthcare cost.

Don’t bring me new technology that just fits in here somewhere but doesn’t help me manage cost. I don’t have the time for it.” And it was just a real awakening experience for these people. But it’s kind of the environment that we’re facing right now.

Think about this. We’re dealing with the left arm and the right arm of the federal government, and med tech entrepreneurs have been dealing with the FDA for products clearance for many years.

Understand it’s a big challenge, but you’re getting to sort of understand how it works. And when you work with the FDA…when you go through to clear your product, you do all these clinical studies among homogenous group of patients who have the same disease, you isolate the fact this is the only condition they have, you take your clinical experiments and you take them to the best universities and the best surgeons in the country to prove that your device is exactly what it’s supposed to do, so you really isolate that treatment effect that you can demonstrate to the FDA that this product really is safe and effective.

But then why in the world then won’t Medicare and third-party payors just automatically cover it? I guess I would pose that as an open question.

I mean, think of it.

The clinical trials happen at the best universities and medical centers and surgeons in the country, but you companies don’t market to just those people.

You market to every doctor and every surgeon, anybody who’s going to buy the product, and they don’t all get the same clinical outcomes that the best university centers in the country do. And health plans know this, medical directors know this.

The variation in the real world is much more dramatic than in a controlled clinical environment. You have a clinically diverse group; you have doctors at all different levels of skill; you have physicians who even though you can’t tell them that you can take this product and use it for off-label purposes, these are smart people, they know they can.

So they’ll take device clearance for one indication and use it for another because they think they can in their practice, they think the art of medicine as well as a science, and these are things that health plan and medical directors have to think through all the time when they’re trying to figure out if they’re going to cover a new procedure or technology. So there are all of these reasons why you’ve got two different sides of the coin. You need to figure them out really at the same time.

Joe Hage: A question for Ed. You showed us the two triangles, one up and one inverted, and there’s the FDA animal and there’s the CMS animal, and you talked briefly about how do we as manufacturers get our code, use more or have the third-party payers be more receptive to it? Maybe you could talk a little bit about that.

Ed Black: I put that under the heading of Marketing to Payers, but you have to get in the mindset of what a health client medical director worries about when a new technology comes out in the market. It is like taking that advice that the product that Elizabeth was talking about, shooting for the world to have this applied to everyone with a related diagnosis. Or Ted mentioned the type 2 diabetes market is huge, and if you think you could treat that whole market with your one new gadget and suggest something to a third party payer, that’s a real fast way to get it denied because there is no device that works well for everybody.

You have to think incrementally. You have to think about explaining and encouraging to physicians the most appropriate use for that technology and suggest that you’re going to work with the clinicians on the uses of your product to continue to use it within its defining clinical indication and not stray too far. Be clear and talk about how it replaces other technologies or other therapies, does not add to the cost, add to the treatment continuum. There are all kinds of things that people worry about.

And in certain market areas, if you take the Blue Cross system, these are plans that are pretty state-specific. And these medical policy directors, they know how physicians in their state practice. You may come out with a great new spinal fusion device, but if it’s in a marketplace or a health plan, medical director knows they’ve got a lot of egress with neurosurgeons and the rate of doing spine fusion surgeries is twice the national average.

They aren’t going to let any new product out of the marketplace until they get a better handle on how physicians are using the device already. So it’s being really sensitive about some of the local issues and trying to get an alliance of creating realistic expectations about the populations that these technologies could serve.

Joe Hage: What is an answer that is, “Yes I have a predicate, but I deserve more reimbursement because…” Is there a reasonable route to go to achieve higher reimbursement if you’re not starting with PMA?

Tom KraMer: That may be more of an Ed question than mine because it’s the idea of, do we go out and fight for a new code or do we not? So that example that I gave of that surgical tool using the RF energy, they decided that it was going to be much less burdensome to redesign or re-engineer the device to use it than it was to go and fight for a new code, and I’ve just seen that it takes a lot of effort and a lot of years.

We’ve got another customer who’s fighting for a new code
for a device that they’re trying to put out, and I think they’ve been fighting for that code now for four years, I believe, and they haven’t…I don’t know if there’s light at the end of the tunnel yet. So, from my standpoint as a design engineer, I said, “What can we do to overcome that hurdle? Maybe it’s we design it so we still get the therapeutic benefit we’re looking for and there’s a unique way to design and engineer that so it fits under the old code.” And that’s my challenge. So I take that on as a design challenge to try to do that, but I don’t know. Ed, maybe you want to comment on that?

Ed Black: In referral to codes, I think you’re talking about CPT codes or the codes that physicians use to describe the procedures they do, and there are three…the three components of the new code, the relative value units. It’s:

• the work expense and the manner in which the technology is used,

• the capital expense associated with the device or the technology,

• and the malpractice exposure.

So if any of those are significantly different, then you’ve got an opportunity to make a case. This is not currently covered or anticipated in how they define this particular CPT code.

So this is…dealing with a client right now. They have an enhanced technology for doing colposcopy examinations.

It’s still a colposcopy but it provides digital imaging and mapping systems that provide for more clear and accurate diagnosis and biopsy.

So we’re making the case that, yes, it’s more expensive, there’s a lot more capital expense associated with it, it’s worthy of additional payment because there’s more time required of the physician and there’s more capital expense.

And oh, by the way, we can demonstrate long-term cost-effectiveness by more accurate biopsies and/or fewer biopsies so, yeah, it’s worthy of being covered incrementally, but then we have to get in this case an add-on code for it because it’s something done in addition to standard colposcopy examination.

It gets pretty technical sometimes, but if the approach is different but the technology behind it is different and you can substantiate through clinical evidence that it does what it’s supposed to do, then you have an opportunity.

And if physicians in a medical specialty like it, make it available to those physicians who practice in that specialty, you get their support.

You have to really get them to become your advocates because they’re the ones who carry the weight in talking to the AMA, which controls issuance of these CPT codes, which is why we’re going to Chicago on Thursday and Friday of this week to talk to some of the medical societies on behalf of a couple of clients just so they know what’s coming out of this technology and think about whether they would support elevating this to a category 1 code so it can get paid.

Pat Kullmann: : I’d like to just maybe make a couple of quick comments about your question…I think are important.

I think that in the early-stage medical technology company understanding what your motives and your clients are, not only from an investor’s perspective but from a management or a board’s perspective, are you developing the technology with an exit, some kind of liquidity point to sell the company, get going public?

What are your motives?

Because depending on what your motives are will help to drive you in an ideal or targeted regulatory reimbursement and marketing client to achieve an early objective in milestones that you can arrive at that liquidity point in the timeframe that you want.

So, for instance, in that type of a scenario where—and I think Elizabeth was working with some venture capitalists, and venture capitalists are hungry people who want to see results. They want a 30x return for their money. That’s what they’re in there for, make money, that’s it.

In cases like that when you have a product and let’s say you’re following your 510(k) pathway, the game is to look like the predicate.

When you want to use an existing code, the game is to look like the standard.

When you go to the market, you don’t want to look like the predicate because now you got to go compete against the predicate and the other benchmark for CMS.

So it’s kind of like wearing the two-sided face of a human, you know what I’m saying? The smiley and the sad. At different times you’re going to wear a different face, depending on what your objectives are. Does that make sense?

Doug Limbach: I’ll just follow up on that on the patent perspective, this notion of wanting to be just like a predicate device. It runs in the problems when you’re trying to get a patent on something, you’re telling the patent office, “We’re nothing like that predicate device. We’re completely different.”

And then you got the regulatory folks saying, “Oh, we’re completely like this predicate device.”

There’s a duty of disclosure that patent applicants have to the patent office to make them aware of all of the closest prior art that you’re aware of. And so it’s very important for you regulatory folks to be talking to your patent folks because you’ve got one side talking to one federal agency, the FDA, saying, “Oh, we’re just like this device,” and another side of your company talking to another federal agency, the patent office saying, “Oh, we’re nothing like that.”

That’s probably more than a few companies where you’ve reached your duty of disclosure. If you’re a patent guy, just talk to your FDA person and knew what was being said and make sure consistent things were being said at the patent office. It would have violated the duty of disclosure, which invalidates the patent if you’re not coming completely clean with the patent office.

Bruce MacFarlane: That’s great, man.

Ed Black: And then you tell CMS you want to be paid a third way. You tell the patent office it’s X, you tell the FDA it’s Y, you tell CMS it’s Z.

Pat Kullmann: : Welcome to your government.

Bruce MacFarlane: We thought this might be a follow up question to you, actually. I mean, in the FDA regulatory world, in terms of determining substantial equivalents. When you say it’s similar, you’re saying it’s substantially equivalent.

Well, I’ve had an FDA category that was defined as a plastics-based tissue patch, a surgical patch. The definition was plastic and I got a bovine material that was brought into the market.

Under the category, it was defined as plastic patch, and cows ain’t plastic yet. They’re not plastic yet.

And so my point is that the concept of substantial equivalence that drives how regulatory people say this is similar to that, it has some leeway.

So I guess the question is, does that help us…? If we can say that non-plastic is plastic, does that help you being able to say in a patent, “Aha, I’m like any other patch of animal, so we’re patenting animal-based patch.”

So I don’t know if you have any other comments you’re going to have. I haven’t actually dealt with bumping into this with patents, but I just know that there’s a substantial equivalence, can be very broad, and other times the slightest difference the FDA will say it’s not substantially equivalent.

Doug Limbach: Well, I used to be able to be when citing prior references to the patent office, you know, explain all the differences and the similarities and talk about it.

Now we just keep the record clean, just cite them.

“Here, you need to be aware of this predicate device or maybe even statements or maybe the FDA need to be aware of it. Really it
’s a case-by-case basis of what you do there, but from the patent side of things it’s just the standard is materiality.

Is this predicate device material to the patentability of the claims you’re going after in the script patent application? If you’re anywhere close, it seems material, you just cite it to the patent office and you don’t have to make much of distinction.

Bruce MacFarlane: The other thing about FDA’s regulatory standpoint is you need to be substantially equivalent, which could be interpreted narrowly or broadly by the agency, and then any differences do not raise new questions of safety and effectiveness that you haven’t addressed, you know, the potential problems with testing.

So you can be different and you can even be better as long as you’re not raising new kinds of safety and effectiveness questions. So I’m just again talking here about how that might still, you know, you can still be different in regulatory, support different in a patent and not have the agency immediately reject your product.

And then the other thing though is you can…because there’s De Novo. So you can have absolutely brand new technology. I mean, it can be made out of brand new materials, brand new intended use, everything could be different, and you can still be a De Novo 510(k).

So in some ways I think the issue has dissipated, because obviously with the PMA you can be as different as you want because FDA is brand new, but now with the De Novo 510(k) I suppose the point is it doesn’t matter how different you are as long as you can be a Class I, Class II in risk level.

So maybe to some extent, since the De Novo has come out, maybe this issue…the only reason the issue wouldn’t dissipate is sometimes you can still be very different and still be within the traditional 510(k) where you’re still doing the dance of “we’re the same.”

But again, I think there are ways maybe to give an interpretation of the substantial equivalence from the regulatory standpoint in terms of the impact, in terms of how you’re different and do you raise new questions of safety and effectiveness.

Well, if you do, you’ve got to put them to rest, in which case you’re still different but you’re saying the differences don’t create a problem from the agency’s standpoint.

And again, I haven’t bumped into this in my own practice where I’ve had patent people interacting with me, but it just seems like there could be a way that you can be different for the patents and still not be so different that you get in trouble with the agency.

Rick Satava: My background is I am a surgeon. I spent 23 years as a combat surgeon in the military, three combat missions that I served on, and in 1992 I went to DARPA. How many know DARPA? Great. Alright. So I’m not going to have to explain that. And this is kind of entrepreneurial at its core. Many people look at us and say, “There’s the government’s venture capitalists,” and to a certain extent that’s very true. We’re not vulture capitalists because we use your tax money. We’re simply venture capitalists.

But what I’d like you to do today is to tell you a little bit about the government’s approach, the Department of Defense’s approach, to entrepreneurship and what the process looks like for acquisition, if you will, and then go into a number of the technologies that were developed, some of which I developed and others had done that as well, and a little bit about what I’ve been referred to, which is called the technology harvester and why that has some relevance.

To begin with, a test. How many of you know what this is? This is a biological molecule. It’s an information system and it’s an energy system. Does anybody recognize this one? Alright, well, let me rotate this 90 degrees. And so anybody recognize this? Sure. DNA. It’s about a completely different perspective, and I think that’s where we need to be going. Clayton Christensen said, right, about disruptive visions, if you will. Yogi Berra framed it differently and he said the future was not what it used to be, and that’s profound in the sense that what he was saying that the things that we have learned, the things that we have integrated into our daily thinking, are outdated and probably false. We’re in the Information Age, but most of us were educated in the Industrial Age and there’s a whole different set of perceptions and interpretations that we carry along with our baggage. And our younger generation, of course, gets it. They’re digital natives. I’m a digital immigrant, more or less, and then some people are just digitally dumb.

So the problem that we have is transitioning and beginning to think in the information space. We define that slightly different. You are probably digital immigrants because you really kind of get what information science is all about, but unfortunately, and to my interpretation, most of what the people in medicine and healthcare look at as Information Age is translating what we used to do from a typewriter to a computer or from a written database to an electronic database, and the Information Age is much more profound than that.

So what is a disruptive vision? An example here of course is Henry Ford, and I love the quote that he gave. He said, “If I asked people what they wanted, they would have said a faster horse,” and that is true today. It’s about understanding what the fundamental question is and what they’re really asking for. They weren’t asking for a faster horse. They want to get from point A to point B quicker, and the only way that they knew was to go ahead and speed up the horse. But if we look at, what is the evolution of point A to point B? If you had a book and you would want to take it from point A to point B, you would walk it, and then we got to a point where we could ride animals and get there faster. Then we had carts and vehicles and we could hold a bunch of them and move them even quicker with multiple animals, then we got mechanical vehicles, and then a disruptive vision hit – the ebook. We can have everything that you want from a book on your Kindle or on your iPad without physically sending the information that’s key to what you want to know from point A to point B. Simply download it in 30 to 60 seconds and you have it available. And this entire chain that we have built up over thousands of years of taking physical objects from this place and taking to that place is completely revolutionized. So this is an example, if you will, of the power of the Information Age and really looking at the fundamental principles, how it is different.

So in my role as a technology harvester, [00:04:48] horizon scanning, I have the opportunity, because of the 12 years I spent at DARPA and the four years at medical research [00:04:56] come in, to get into many communities. I’m a trusted source in the sense that, as you well know because we were responsible for classified material, people would trust us with their information, we are walking NDA and we have access to the broad spectrum. Whether it be from academic, federal labs, FFRDCs, businesses or various large industries, we have access to, and the opportunity there is to share information, particularly information or new ideas and concepts or technologies that most people don’t have the opportunity to do. And these are a number of the things that we use for that, not only literally visiting place to place or going to conferences such as this one to get a broad perspective, but also the opportunity to go ahead and have access to the wide variety of databases that are there, and quite frankly many people continue to send information to us hoping that will stimulate new ideas and so forth.

One of the things that I learned about at DARPA was when you come up with a new idea, one of the first things that you want to do is, so what is the standard that we have today? The standard is basically the best of breed is a 360-degree view. Look at it from all different perspectives, the users and the manufacturers and the company and so forth. But I think that one thing that I was talking about at DARPA is we need to take the 180-degree view, which is what? You look at what the current standard is and assume that’s exactly the thing that you do not want to do. You want to start a new business with exactly the opposite.

And this came out of Clayton Christensen’s book, although he never really spoke about it. But if you read from his book what he used as examples like large [00:06:51] to small [00:06:52], crane operators to backhoes, steel industry to micro steel industry that went to Japan, all of these took what is the standard that we use today, what is the way that our customers tell us we want and this is how we want to do things and look at it from entirely different perspective, which is why I showed you DNA in the beginning. So this is a methodology that you can use. Can I do exactly the opposite of what’s available today and get a better product out of it?

So it’s about rethinking the status quo, and this is what I think our greatest entrepreneur of this era, Steve Jobs, was, and his quotes I think are also very telling. So time is limited. Don’t waste it living someone else’s life, something that’s already been accepted and everybody believes in. Don’t be trapped in dogma, which is living with the result of other people’s thinking. Be innovative, be creative. So this is the direction that we need to go, I do believe.

So in healthcare, what do we want? There are expectations out there by our patients. I remember a year or so ago sitting down with a patient that had a hernia and they wanted to start off by showing me the other children’s pictures and their vacation they went on, and finally I got them to say, “And why are you here?” “Oh yes, I’m here because…”

And then when we decided what it was, she said, “Okay, what do we do now?” I said, “Well, I need to do a final diagnosis.” And so she said, “Oh, we need lab test taken right now.” And I said, “Well, I have an ultrasound and I can look at it.” So I, “Oh, you’ve got an ultrasound and you do have a hernia there.” And she says, “Great. What happens?”

And I said, “Well, this is going to need surgery.” She said, “Well, can we do it now?” And I said, “Well, this one we’re going to have to schedule. I can’t do it right now, although maybe in the future I’ll show you high-intensity focused ultrasound that may eliminate the need for actually doing surgery on it. But I can’t do it in my office now.”

She said, “Okay. And it’s not going to cause any pain, is it?” And I said, “No.” “And when I leave I’m going to be cured, right? I won’t have to come back and ever see you again, will I?” And I said, “Probably not.” And then she said, “Okay. And could you hurry up? I’ve got to go pick up my child from a soccer game today.”

So this is what we want, and I think this is what everybody wants. Why did I go through this here little story? And the reason being is that this is a benchmark that we want to see how close we can come to
with a product.

We want to meet our patient…or our users’ expectations, and the closer that we can get to their expectations; the easier the sell for the product is going to be. But our expectations are high, but now our challenges are getting even bigger. There are significant changes in the population as a whole and some of the approaches in the past are no longer as applicable as they used to be.

So let me tell you a little bit about understanding research as part of the entrepreneurial enterprise and show you where we go on that in terms of new technologies.

In the military, they call it the acquisition process. It begins with, say, a soldier who says, “I need a new helmet that’s laser-resistant.” “Well, I don’t have one of those.” So we have to begin with R&D. Research and development begins the acquisition process, and then you go through all the various steps as we go along, what is called life cycle management, and using descriptions such as the technology readiness levels. And then when you finally finish it and you get your FDA approval, your marketing and so forth, then you finally have to dispose of it.

So what does that process look like? And I’ve seen the complexity that you’ve talked about particularly when we’re relating to FDA and those types of regulations. This is the Department of Defense, NASA, and NIH’s roadmap for developing a new product, and so this is what you go through whether you know it or not.

And the incredible part about this is when you start talking to researchers and you want to start a new product, they think, “Well, I have this new idea and I want 50 or 75% of the royalties.” What they don’t realize is they’ve done less than 10% of the work and the investments in it. So R&D is really down at the very beginning. When you finally get here with your prototype, then you have to go through the FDA, which we’ve been struggling through with today, and finally you get it approved, but then you’ve got to manufacture, commercial, marketing, and eventually it has to disposed safely, and that’s the responsibility in the business.

I only put this out to recognize how hard your job is. Even if you’ve got a great idea in your new product and you want to move forward, this is just the beginning of an extraordinary, long, difficult, and expensive journey particularly in healthcare.

One of the things that will help you are technology readiness levels. How many people know them and use them? It’s a language, if you will. You can find it on Wikipedia, which is a very nice, simplified version of it.

But if you want money, particularly if you want it from the Federal government and any of them, if you can go ahead and tell them using the terminology in the levels here, it will be greatly to your advantage because what you’ll be able to do is submit a proposal in a language that the program managers understand, because they get money depending upon the level of readiness of your technology. It will do you no good to submit a proposal to DARPA to do a clinical trial because by law they are not allowed to do it, so why bother submitting? No matter how revolutionary you may think, we have to go to medical research commands and so forth in order to get that color of money.

So I just want to put this out that there are ways if you learn the language to increase your likelihood of being funded. And we know the role of the scientists in the development of a new product and of the different people that are involved in there, and there are a couple of chasms in there. There’s the Valley of Death, which I’ll show you in a moment, and then there’s another one, a second chasm with after you got your product the expectations frequently are higher than what you can actually match. It’s been overhyped by the media and so forth, and that’s another area that’s very difficult that very few people pay attention to.

So this is what the Valley of Death looks like. The government will help or outside people will people help you with funding, but then you get to a point in time where the government says, “Well, this is far enough along. You need to create a business or you need to find an exit strategy.” But on the other hand, those who are investing in you want it further funded. They don’t want to take the risk that’s in here and we end up with what we call the Valley of Death. And so this is very common. People have known about these for decades.

What most people haven’t paid attention to is the second valley, which is the second chasm, and that is you’ve got everything you’ve got, your FDA approval, you’re ready to go, and you go out marketing, you find out nobody really wants it after all. It’s kind of been overhyped, if you will. You can’t meet the expectations. And it was Gartner who brought that to our attention, if you will, which is Hype Cycle and the sense that you start with the new technology and people see it and they have these great expectations on what’s going to happen, and then you don’t meet those expectations and then it begins falling down. You have to do the hard job of the research to validate that in addition to getting the product out, and finally it actually gets out in there. So these are some of the issues that I see as challenges and barriers to actually getting what would appear to be a simple, new innovative product actually out in the marketplace.

So enough with the boring stuff, let’s have some new toys. And so what I’d like to look at as a different way of technologies that you might want to look at as something that you can take advantage of, something that may leapfrog you and put you out of business. There are technologies out there that I think that are coming most people aren’t aware of, and they’re either complimentary to and you should see how you can integrate with them, or they’re going to be competitive to you. Few of them will be completely irrelevant to where you’re going.

One of them, and my area of interest, is robotics and robotic surgery. Here is the system here. I would commend to you that you think of this not as a medical device. This is an information system. It happens to have arms and legs and so on and so forth, but in the paradigm of the Information Age. What’s really important about the robot are not the parts but it’s the software that controls it. Without the software, it’s safety factors, the redundancy, failsafe, graceful degradation, and so forth, that robot is truly useless. So it’s a combination not only of the physical device you’re doing but the information system that controls it.

But the beauty of that is that this is an information system and it’s one that nobody’s taking advantage of. I’ve seen a lot of talk about approval processes and so forth. I haven’t heard a lot about sharing information back and forth across the electronic medical record. The electronic medical record has been talked about, but this is a device as an information system that generates information.

The first time I operated on a patient without ever looking at them was when I did laparoscopic surgery. I never saw my patient. I looked at a video image, which is information about what’s going on inside. The first time I operated with a robot is the first time that I not only saw my patient but I never touched them. I moved my hand, the electronic signal information went and it cut, sewed or whatever I told it to do. So I became an information manager, if you will.

And if you look at other devices today, your CT scanner, that’s not a digital imaging device, that’s an electronic information eye, if you will. And if you look at the things that you’re doing from the perspective of an information system, these are things that you cannot physically integrate but you can if you use the information systems that control them.

The interesting thing about a robot is that it’s bought by an enterprise, usually a hospital of some sort, but it’s used by their physicia
ns. There is an enormous amount of data.

Big data is generated during every single operation and not a single piece of that is used. Why is it that every time I do an operation and I’m finished, I have to go out and dictate an operative note? The robot knows more about what I did than I actually can remember. We should be able to collect and automatically print out an operative report.

We have to change instruments. The da Vinci is only allowed to have five uses, and then you have to throw it away. And it automatically can communicate, although it doesn’t directly with your central supply for just-in-time inventory and so forth. Very, very few healthcare use the systems that have been set up in other areas as well. So this is just to emphasize that there is an enormous opportunity from the devices that we have and the communication back and forth between them.

We decided that we were going to go ahead and not only build the robot but see if we can build an operating room based on manufacturing principles in which we got rid of everybody in the OR except for the patient.

And when you think about it, what does my scrub nurse do? Well, she changes my instruments. Well, we have tool changers for that in industry. And what about my scrub nurse? Well, she gets new supplies and so forth. Well, we have supply dispensers, automatic. So we built an operating room with no people using the currently available robotic system but it’s generic and it can be used with some other systems as well.

And so I would say, “2-0 chromic catgut,” it would go to the dispenser, bring out the suture material and hand it to me if I were ready. If I wanted to change my instrument, I’d say, “Scalpel for the right hand,” it would grab the scalpel, wait until I held out my hand, removed the clamp, and replaced it with a scalpel. It can do this in 11 seconds and it can do it with 99.96% accuracy, almost as good as my scrub nurse.

So we have systems that are available there and they’re trackable, but so far we haven’t moved forward in them. So why would the government spend 30 to 50 million dollars building systems like this? Well, one of the problems that we have is the “far forward battlefield.” We don’t have a bunch of doctors and nurses there but we do have a few medics. So here is the concept video that resulted in developing robotic surgery and the operating room of the future until we go to the next generation. The scenario is what would happen when a soldier is wounded out on the battlefield away from medical facilities? Well, we have a robotic extraction vehicle that you see here, we have two prototypes of that, and we put our robotic operating system with telemedicine into an armored vehicle, a Bradley 557A. Then we began what would conceptually be robotic surgery for damage control on the battlefield. You scan the individual to see where the damage is and send that information back to your surgeon, and then the surgeon can begin operating. If you need to change tools as I showed you, we have the tool changers, and if you needed new supplies—and this represents fibrin glue to stop hemorrhage—we would have those available as well. Not only are we using mechanical instruments but we’re going to more and more towards energy-based systems, things such as lasers and ultrasound, plasma and so forth, which I’ll be talking about shortly. And then when everything was completed, you automatically evacuate the patient into an unmanned air vehicle to the closest MASH hospital.

When we developed this concept video in 1995, everything that you see in that video was available to us in industry. We did not have to invent a single thing. It was a matter of systems integration. And so we did not have the opportunity to complete this because we demonstrated it can be done, and they said at DARPA, alright, our job is over. We invented something new and we proved it could work, and we moved it out into medical research command. The budget came, R&D got slashed, and so now this is on the shelf collecting dust. But the concept is valid, and whether or not we do it no longer is a technical issue but it’s rather one of, “Do we want to really do this? Is this going to be cost-effective? Are we going to have a market?” and so forth.

So, many of the things that we have out there we have been working on for a generation or more. For example, we funded UC Berkeley and Robert Fuller’s lab and Eric [00:21:54] working there on a cockroach. I mean, I hate cockroaches, but anyhow, it is the most efficient motion machine on this planet. And the concept was, if we can learn how this could be so efficient, perhaps we could run our robots better. One night, students snuck back into the laboratory, they disconnected the recording wires from the probes in its brain, connected them directly to a joystick, and began driving the cockroach around the laboratory. Three-and-a-half million of your dollars to drive a cockroach around a laboratory.

But imagine—look at your cell phone, you’ve got that tiny little camera—imagine if we would have put those on, say, a thousand of these little cockroaches and sent them into the World Trade Center, into Haiti during the earthquake, to the tsunami. I mean, these can go places that people or even dogs can’t go. They probably could have found many, many people that were trapped under there perhaps, saved hundreds if not thousands of lives. So maybe it wasn’t so stupid after all. But that was the beginning, if you will, of the biomimicry and the bioinspiration efforts at DARPA.

Here is another one right now that is being developed at the University of Washington, [00:23:05] Daniels laboratory. This is a moth, a sphinx moth, but when it’s in the pupa stage they open it up and implant a transceiver, a receiver and transmitter. When it grows up, it grows in around the neural crest and it actually embeds it in there. And so these little moths now, they’re not very little, they’re about this big, when they grow up and they emerge from their pupa, you can actually fly them around remotely like you would find an airplane, but it happens to be within a living system. So we’re beginning to integrate, if you would like, the capabilities of biological living systems and the mechanical systems that support them.

And you saw earlier the given capsule – this is what used to be an endoscope. I see some of you [00:23:54] squirreling around, you know. You’ve had your colonoscopies and you know how hard it was. Well, now we broke the tip off of it, embedded everything into the tip, and you swallow this pill, and as it goes through every 30 seconds it sends a picture to your belt-worn computer. And about 18 hours later it’s passed, you take the video, give it to your gastroenterologist, and he will be able to go ahead and make your diagnosis. So we’re moving biomimicry, if you will, away from large devices that we use to smaller devices that mimic some of the functions that are biological [00:24:29].

And here was the next generation “the ability to control these,” if you will, a couple of large EU projects running around five to 10 million dollars per year, multinational ones, and these are some of the devices they began building. This is one that kind of crawls around inside the abdomen or chest, has manipulators, and it’s actually able to operate on things. Whereas this one would be in a fluid-filled cavity like the bladder somewhere, and so you can’t walk around, you kind of propel yourself around. And this might be for inside one of the lumens like in the colon somewhere and it’ll wiggle its way through. So they’re looking at different ways and they can make [00:25:05] them extraordinarily small like this tiny one that you can actually put into blood vessels and allow it to swim upstream and so forth. So we are looking at how far can we get smaller devices into the body and be able to do therapeutics with them.

Femtosecond lasers. Who knows what a femtosecond laser is? Yeah. Who cares what a femtose
cond laser is? Yeah, I care. And why do I care? Well, a femtosecond laser is you shine on laser light and when you pulse it really fast, a femtosecond per pulse, which is 1 x 10-15 seconds, if you take this pulsed light and you put it on an individual cell, you can make an incision and open it up and begin operating on the individual parts inside of the cell, mitochondria and so forth. At the University of Dundee in Scotland, they’ve actually gone ahead and gotten into the nucleus, removed bad genes, and replaced them with good genes, giving a new definition to what is genetic engineering. You can do that today and many biologists have been doing this for well over a decade by using some of the computer-controlled systems that we’ve got available to give them micron-level proficiency. However, we have that because the current robotic system that we have, it’s accuracy is 10 microns, which is enough to allow us to operate on individual cells if we would choose to do that. No one’s explored that area. They’re very busy from a business standpoint increasing the revenue and getting enough robots out there at this point in time. But this is an unexplored potential that we may be able to use because the precision of the robot will allow us to do something we have never been able to do before.

And here is an example from Dundee. This bright spot is a gene that has just been replaced and these other genes here are other genes that are defective that can be replaced as well. Where most of this activity occurs is at the cell membrane. And this is an ion channel, and this shows you that we can actually stimulate the ion channel to open up and we could put individual proteins, transcription factors and markers one by one into the cells that we would choose.

So when we start looking at these and we start using things such as femtosecond lasers and radiology with the precision of tenths of a millimeter, is this now surgery or is this radiology, or what is it? Is the future surgeon going to be somebody who sits behind an x-ray screen and use this, for example, something like the CyberKnife that allows them to get an accuracy of 0.1 millimeter on tumors and so forth? You can couple those with markers, individual markers for individual cells, so that only the cells that are marked are the ones that are going to be damaged.

And so we’re looking at developing hybrid operating rooms that are a combination of imaging suites as well as surgical suites, and we’re seeing the beginning of the appearance of these. These are extraordinarily expensive because you’ve got the big expensive CT or MRI in addition to the expensive operating room. So rather than spending four to five million dollars, we’re pushing the limits up to seven, eight and 10 million dollars just for the basic operating room that’s a hybrid operating room. We’re not sure where it’s going but it looks like there is a pathway to the future, which I’ll be talking about in a moment.

But I’d like to just finish with robots because I love them so much. They’re so cool. DARPA has a new program, the rescue robot, if you will, and [00:28:52] this, it’s anthropomorphic. It looks like a human. We don’t need a robot to do that, and besides, we can’t build one. And then a friend of mine, Mark Raibert for Boston Dynamics, built Petman. This is probably one of the most sophisticated. His next generation is called Atlas and it’s being used. But this is a [00:29:13] program that is not programmed. This robot has modules called subsumptive architecture in them that communicate with each other. You give it a high-level instruction, go from point A to point B and pick this up, and come back. And it navigates its own way. It’s able to go over different obstacles, if you will. If it’s bad, [00:29:34] it has to do it’s pushups, if you say here. But it’s truly the next generation. It’s got about 10,000 sensors on it, it’s got [00:29:41] a brace that’s a good AI program that helps control it, and you saw the next generation of robots, where we’re going.

So these are the things that we have there, things that are going to be coming out. We don’t have to invent them. They’re already there, and the question is, how can we implement them? Can you integrate this in your overall plan for what you would want to do? Can you build things that would supplement this and be part of them rather than be replaced by them?

So our current trends today in intervention have started with open surgery and luminal surgery, then minimally invasive like laparoscopy, multi-invasive, which was robotic, and where we really want to go is to noninvasive. And we’ve had our instrument development on there and if you look toward the end there, now that we’re robotic, what comes after robots? The next generation, I believe, is something called directed energy surgery, and this is significantly different because it allows us to do it noninvasively. I’ve showed you one or two of the opportunities that we have, say, like with the CyberKnife. That’s noninvasive surgery. Kill the tumors, kill the things without having to make an incision. The patients love this because there’s no pain involved. They come and then they go out as an outpatient and so forth.

So we have to rethink how we’re going to do therapeutics or interventions, if you will, and I believe it’s the flow of information that controls energy and that’s going to guide the future of most of our procedures. The fundamental change is going to go from physical objects, if you will, [00:31:14] tissue with instruments, the tangible things that you feel inside you, the devices will go to intangibles like information and energy and the interaction of the two of them. So it’s about exploiting the energy spectrum and the information space, and I think that’s a new definition for what is the Information Age. This interaction is key.

The electromagnetic spectrum is out there. I mean, we’re surrounded by all forms of energy. It’s this big. Industry is using this much of energy in x-ray, ultrasound and so forth. Medicine is using about this much. The opportunities are huge if we can control the energy with the information, and that’s the direction that we would need to go. This is about all we’re using at this point in time of this massive amount of energy that’s out there and how we can exploit it.

So I think the time has come, and the reason I think the time has come is because I saw this video is because I saw this video by the Navy. Instead of sending their destroyer out with 80 people about 120 million dollars in cruise missiles, they send them out with eight people and one laser, and then they challenge them with 20 different unmanned air vehicles, and from two miles away they were able to destroy within three seconds each of those that were coming towards the ship. They weren’t even within range of their missiles that they carried. So the point being is that we’ve got the systems, particularly the control systems that I mentioned, that are so important. If I can control a device to focus on approximately one square foot and follow that and track that for three to five seconds, certainly I can have a desktop device that will look down at the micron level. So we have the capabilities to do that. We’ve been testing them in the biological field, in cell biology with genetic engineering. Why this is important is when you put the two together, the device that you’ve developed and software to control it, you can develop a single instrument that performs diagnosis and therapy in real time at the point of care in a handheld, portable and low-power instrument that eventually could be autonomous if you put closed-loop feedback into it, and eventually it may end up as a home consumer product.

So let’s digress for a moment why this is important, what the implications are. For about 2000 years since Protagoras made the statement, “Man is the measure of all things,” we have used man as the measure for all things. How many feet did you walk to get into this room? How far is a yard or a m
eter? Well, actually in 1453 it was defined the distance between the nose and the tip of your finger by the silk industry, and what they would do is they put the bolt of silk up and they grab it, and they’d go one, two, three. Those were the measures. And when you look at it, until just recently, everything has been on the macro scale, but in science we’re down on the micro and all the way down to the nano scale. We have a new way of perceiving the world, one that we never had before. Sure we had microscopes and we had telescopes to increase our view of the world, but that was only for a few very, very special people, but now in the future we have the opportunity to move to a totally different scale.

And Richard Feynman was right in 1959. He said, “The future is in the world of the small.” That’s where we’re going, and for the first time we have the capability not only of diagnosing or looking at this but actually manipulating at that level. What makes it possible, it’s a combination of information and energy that results in an intelligent system. So for engineers that are out there, if you send some form of energy into anything that’s living system, you perturb the system. For example, if I shine a light onto a cell, it either absorbs or transmits it, and the difference between what I send in and what comes back is going to be my diagnosis because each living system is totally unique. So I can make a diagnosis by shining a light, shining an ultrasound, shining a terahertz millimeter wave, any one of these spectrum of energies that are out there, and then I could make a diagnosis from it. But if I take that information and immediately feed it into a device for turning on and turning off, say, a therapeutic modality like laser in order to cut and coagulate high-intensity focused ultrasound for ablation and so forth, then we end up with a closed loop. So I can send in a test to find out what my cellular diagnosis would be, and then I can ablate that particular one or I can enhance it, I can give it an extra energy to change the level that it’s moving at. This closed loop is a very profound change because this now makes my instrument intelligent. It will know exactly what the configuration of every single cell is as it queries each one.

So with this, we can do a closed loop in 50 milliseconds, but what does that mean? As a surgeon, that means I can do 20 complete operations in one second or in a minute I can do 1200 complete surgical procedures. I can’t even do 1200 in a year, and here now I’m telling you I can do within one minute 1200 operations, but it’s at the cellular level. The reason that that’s important is that we can identify cell by cell whether it be cancer, whether it be inflammatory bowel disease, whether it be wound healing, to either destroy, apoptosis or ablation, or to stimulate, angiogenesis or VEGF or some of these others that we know that turn healing mechanisms on, and we can do it cell by cell just by sliding our instrument over it, if you will. So it gives us the opportunity to use energy to control the biological processes for either destruction of tissue or for healing of tissue.

So here are some examples of what we have available. High-intensity focused ultrasound. That yellow dot went on. Let’s see if I can run this again. And when the yellow dot goes on, the ultrasound coagulates the tissue inside of the lens without causing damage to the outside. It’s called an acoustic window. You are able to focus it to a point so that the only damage occurs exactly where you would like to have it, and you could measure that, you can modulate your energy to the frequency, the power settings and so forth, to the exact depth and precise point that you would like to.

[00:38:18] is very interested in that. Using their hemorrhagic model, which is to lacerate the internal iliac vein inside the abdomen of a pig, every one of the pigs that you would lacerate, you would cut this vein, they would bleed to death in 15 minutes, 100% mortality. So here you see the Doppler image of that vein being cut, the artery being cut, and now it’s bleeding to death. But we had the high-intensity focused ultrasound, so they pressed the button and they looked, couldn’t see…oh, there’s a little bit [00:38:50], so they went ahead and pressed the button again, and what ended up happening is when they checked it there was no more bleeding. Normally, this would be about a one- to two-hour operation, and they were able to do it in less than a minute without causing any incision whatsoever.

Imagine if someone’s out on the highway and they’re injured, they’ve got blunt trauma, they’ve got a tear in their liver or their kidney, a medic runs up and goes, “Hmm, well, I see where the bleeding is,” and presses the button and stops the bleeding and the patient is cured. Star Trek, anyone? No? It’s a new technology that we’ve been developing based on the premises that I’ve told you about information and energy, and we could move further in other directions as well.

An area that is a great excitement to me that’s brand new, it was approximately six years ago something called cold plasma was discovered by the physicist. Normally, plasma means, what happens when lightning strikes? It energizes [00:39:53] all the air and it converts it to its more elemental forms of energy. So it destroys the product but it creates energy in its place. And so someone just recently discovered how you can do that with low power without all the fancy other equipment like vacuum and noble gases and so forth, but simply by pressing the button you can create this plasma. Why this is important is that we now have enormous amount of free energy that’s there that you can begin manipulating biological systems.

In the cloud that we create [00:40:27] from, it’s a little purplish-colored cloud, you can see it right there, we have charged particles and free electrons. We’ve got reactive species, nitrogen and oxygen. These are responsible for our most basic biological principles. These are the things that turn on and turn off most of the mechanisms that we see that are used in medicine. We use drugs to carry various types of drugs into the body, and what do they do when they get there? They react and cause these electrons to move or the reactive nitrogen species to interact with the systems. We also have UV light. We have high temperature, electromagnetic pulse which is responsible for disrupting adhesions between cells. So there’s this energy that’s in there and we’re beginning to realize that our biological process of life at the molecular level has to do with moving around electrons or other forms of energy, and we now for the very first time have instruments that not only can detect what’s going on but we could add or subtract energy from it and actually turn on and turn off specific molecules. This is a revolutionary concept. Right now plasma is limited to the surface. We’re using it for things like sterilization and wound healing, and we’re looking at other areas. We can selectively turn it on and turn off. These are the things that we’ve been able to turn on and turn off like angiogenesis for healing. We can also incite apoptosis.

An interesting thing is that high-energy plasma in the past had been used for sterilization, but it was too difficult to use. You had to have monster instruments and so on and so forth. We’ve discovered that cold plasma does the same thing that hot plasma does, and why is that exciting? There is no known biological agent that is resistant to 30 seconds of exposure to plasma. Can I repeat that? No known biological agent that is resistant to 30 seconds of cold plasma. We’ve investigated it. We took blood samples from our soldiers that died in the battle [00:42:36] from overwhelming antibiotic-resistant bacteria, subjected them to these, and it killed every one of them within 30 seconds, and we would repeatedly take the few that weren’t killed, [00:42:53] them, and through multiple generations, at least six generations we have data on that they cannot develop
resistance. And this plasma does not injure cells. The going hypothesis on that right now is because our DNA is controlled inside of a nuclear membrane, which has a number of important chemicals in there like [00:43:14], which destroys nitric oxide and prevents it from damaging. But all other known biological agents don’t protect our DNA or RNA, and therefore they get totally disrupted by this process. We have to learn more about this. This is only six years old. It didn’t exist six years ago, so the opportunity now is enormous to be able to move forward.

So these are some of the things that we’re already looking at and investigating for clinical applications, if you will. Am I getting close? Ooh, I got to hurry up here. The University of Tennessee just discovered that they could put a marker on a brain tumor and then they would shine a specific wavelength of light into the skull, activate the markers, and kill the brain tumors. So now we know how to kill brain tumors cell by cell that are individually marked without even doing surgery, without giving you terrible poisons like the ones that we use in chemotherapy or immunotherapy simply by marking them and giving them the right light. This has been going on for a long time.

Here is food processing, to give you example of what’s out there. The chickens go past for inspection. Before, they used to have one check in every hundred. You would swab it, in two days literally you’d find it. Now as each one of these chickens go by, they rotate around and they do two-and-a-half chickens per second. They laser-scan them, not too different from this laser scan that you got in the grocery, match it to a database and determine whether or not any one of a hundred different pathogens are on there, and they go through this. So we should be able to in healthcare leverage off of this. And they also have coupled it for automatic milkers and so forth. So I think what the future is looking at is a combination of image guidance and intelligence systems with energy to take us to a noninvasive form of therapy, which we’re calling directed energy surgery.

So I have a few more…how much time do I have? I’m getting close.

Alright. [00:45:39]. These are probes that we put into the brain of monkeys, and these monkeys, what we would do is we would teach them if they would move the red dot to touch the green dot, a robotic arm would come and feed them. It takes about six weeks to process the signal, pretty much like we did with the cockroaches, but then what we did is exactly the same thing that happened with the cockroaches. You take it away from the recorder, you hook it directly to the robotic arm. It took the monkeys about two weeks to realize they didn’t have to move their hand in order to get fed. They just had to think about eating and the robotic arm automatically fed them.

So this was translated into an IRB-approved protocol in a quadriplegic that you see here, Mark, at the Rhode Island VA. He has the probe in his brain, he’d had it for three months, and Mark drew a circle, and so you see he’s trying to draw a circle with his thoughts. They made a little program so he doesn’t have to call the nurse every time he wants to turn the television on or off or to change the channel, and so here is Mark turning and turning off the television, changing the channels and the volume and so forth.

One of the students ran down to the prosthetic lab—this wasn’t planned as part of the research—and hooked up the prosthetic hand, and said, “Mark, can you open and close this hand just by thinking?” It took him about 15 minutes but as you see now in this raw data, the first time that a human ever opened and closed a prosthetic hand simply by thinking. So DARPA began its next-generation intelligent upper arm prosthesis and it’s in progress at this time and it will eventually be able to be connected directly to the brain. But perhaps we’ll be able to provide a device that sends the signals without putting probes into the brain. Now, this is going to be extraordinarily hard. The signal-to-noise ratio is so low. But perhaps five, 10, 50 years from now we’ll actually be able to have a device you could pick up the individual thoughts and be able to control devices with them.

And we may be even sooner than we thought. This is a very interesting experiment out of USC. This mouse has a tiny little 50-micron fiber optic probe in its brain, and with that they were able to look at the cells, see which ones were firing off, and they discovered that there was a pattern: Every time he turned left, they had these specific neurons that were activated. So what they did was very similar to what was done in the monkey. They focused it on each of those neurons and he was walking around at random, and then they started stimulating the neurons and the mouse started [00:48:13] turning these left-hand circles exactly as he had thought. So they said, “Wait, that’s really cool. I could make him do what I want to do.”

But the next thing that they did was even cooler, and what they did is they sensed when he was going to turn left, took that and sent it over to the second mouse. And so every time that this turned left, he made this one turn left. He sent his thoughts from one mouse to the other. What would we call this? Mental telepathy, anyone, sending a thought from one person to another? We may be on the threshold of some new way of discovering information and transmitting it. So don’t invest too heavily in your cell phone companies. We may have something else coming forward.

We’re replacing body parts, if you know, and we’re growing new organs. We’ve had clinical trials that demonstrate if you harvest the patient’s stem cells, you grow the new organ and you take out the bad one and put the new one in, they do not reject it. They now have an organ without having to go through chemotherapy, immunotherapy and so forth. This is truly profound.

As a surgeon, I know 23 operations to operate on your stomach. What am I going to do in the future with this technology? One operation for your stomach and only one. No matter what’s wrong with your stomach, I’m going to take it out and give you a new one, one of your own that you won’t reject and you don’t need chemotherapy for. And all other industries except healthcare do this. They take your car in, they don’t fix anything anymore. They find the bad part, throw it away, and give you a new one. Time for healthcare to catch up.

And we’re looking at printing these organs with 3D printers, and 3D printers are going to be a revolution beyond just healthcare and we need to be part of that. For example, in our fundamentals of robotic surgery, we had to develop a new system and a new device in order to test how well people trained in robotic surgery. We built it with a CAD/CAM and then we printed it out, and now the people can have in their training center not only the device but they can print new parts. They don’t have to go out and order any because all they have to do is reprint them from them.

So [phone rings]…don’t you just hate that? I thought that was off.

So I think the 3D printing is going to be a huge step in the future, and it has applications already that are just beginning to surface in healthcare, replaceable parts that are printed out that are patient-specific as you see here. And as Dan showed you, we can print not only biological parts but electronic parts together as a single device as in the lower right-hand corner. It may be more important than the Internet. But think about this: If we can do things like create organs and dispose [00:51:07] and patient amenities, if you will, right in the hospital, we don’t have to have people manufacture them for us and ship them all over the place. There’s no delivery, minimal inventory, it’s just in time, custom-made, and you can recycle it locally as I’ll mention here in a moment.

So here are some things that…how much do these cost? Probably cost pennies to manufacture an
d they cost us about 125 dollars for them. If we print them locally, we have them when we want them, don’t have them standing around, we can sterilize them with plasma or some other form and use them immediately. So we have an opportunity now to get the relatively straightforward, low-cost 3D printers, make them available, and create the things that we need when we need them.

This is very interesting. There is a company out there called Filabot, and what it does is it takes old materials that were used to print things, reprocess them into the filaments, and allows us to go ahead and use that to print something new. It’s kind of like the ultimate recycler, if you will. If you don’t like the piece of equipment you have, you put this through the Filabot, you reduce it to its basic chemical processes, and then you feed it back in. Talk about something that’s going to revolutionize the way things go. There are certain products like milk bottles and so forth that you an reprocess, use them into the Filabot, and create things that you would want or need. And so I think that that’s going to be one of the huge advantages in the not too distant future.

I’d just like to mention suspended animation because I think this may be the opportunity to replace, if you will, anesthesia. Brian Barnes in Alaska discovered that the Alaskan ground squirrel does not hibernate because it’s cold, it hibernates because he turns himself off. We don’t know what the signal is that turns him on and off; however, it activates the hypothalamus to send out a chemical that goes to every cell in the body and basically turns him off.

And Mark Roth discovered a way to do that with hydrogen sulfide, and I watched him one day in the laboratory when he put a mouse underneath the ground and gave him some hydrogen sulfide gas, and he was dead in three minutes. I said, “Mark, dead.” He says, “Yeah, I know.” And I said, “Well, what do we do now?” He said, “Go for lunch.” Alright. So we went out for lunch, saw a couple more experiments, came back about four, five hours later, “Mark, it’s still dead.” And he said, “Patience.” He takes the top off of it, he whips it up, gives it a little bit of oxygen, and the mouse wakes up, looks around—he hadn’t had lunch—finds the maze, runs through the maze, and starts feeding himself. So we think that he was completely intellectually intact.

So what does this mean? I said, “Mark, what’s going on here?” And he asked a question. He said, “What would you do in your life that takes the most energy?” I know what you’re thinking. No, it’s not sex. It’s dying. Because we have something called the agonal gasp. At the very end, you shut everything down, you’re basically auto-digesting your body in order to create energy to save your heart, your brain, and your kidneys. And so according to Mark death is an auto-digestion, but he said, “If I block all the enzymes that are needed to begin the auto-digestion, you can’t die. You’re not alive because nothing’s moving, but you can’t die either.” And he said, “The only thing I can give as an explanation for this is this is a form of suspended animation.” So far he’s had it up to two weeks in small animals like rats, and he’s beginning his large animal trials as well. And he’s converted it from a gas into a liquid form that he could actually give IV. So this is going to be an exciting area to look for, and I’m excited because if I can use that I won’t have to worry about my patient moving, my patient won’t bleed while I operate, and certainly it will numb the brain to a point that he can’t remember anything. And when surgery’s over, we’ll reboot the system.

So, do I have two minutes or do I need to stop? Okay. Because the most important…oops, sorry, that wasn’t [00:55:20]. I keep on putting that one in. Is that we have to make sure we do the research so that we don’t have some unknown, unintended consequences. But this is raising the issue. The technologies I’ve showed you are raising the bar on the moral and ethical issues. We human cloning, we said we can’t do any of it. That’s not the answer. We now have genetically engineered children. And so the question is…if you have a child with an abnormality, the government’s going to ask you to have another child, to harvest the cells from that one and give it to the genetically deformed, disabled person so they can have a normal life. The question is, what happens if the family doesn’t want to have another child? Is the government going to be responsible for taking care of this poor, disabled child for what few years they have left in their miserable condition at hundreds of thousand dollars a year rather than giving them a short 30,000- or 40,000-dollar procedure and giving them a normal life? Who’s going to make that decision?

We know at least three ways to extend the life of a mouse –apoptosis, anti-telomerase. What happens if I do? I could give it to your granddaughter. Now, she is going to live three times, 210 years. What is that going to mean? We heard from Eric Rasmussen about the problems that we have with increasing population. What’s going to happen when people can live for 200 years? Who’s going to get this technology, everybody or just limited to certain persons? It’s here. Should we use it?

I said we can grow any part and I said but except for the brain, but in Vienna we got people even trying to grow the brain. So I can replace any part of your body, but the question is if I do, are you still human? What is it that makes you human, this flesh and blood that you were born with that I can now replace or is it something more?

So I would like to close—and thank you for your tolerance—with probably the most profound question that our technologies raise today, and it comes from Francis Fukuyama’s report to the biomedical commission from the president and he turned into a book called Our Posthuman Future. And this is what he thinks is the most profound question, and it’s for the first time in history that it walks on this planet, a species so powerful that it can control its own evolution to its own time and own choosing. That species is Homo sapiens.

That’s not a patient species.

We’re not going to wait 500,000 or a million years to evolve into something new. So I ask you, “What are you going to make as the next species on this planet to follow man? Because that decision is up to you.”

Carrie Kuehn: So, what is FDA’s refuse to accept policy? So, FDA developed some criteria for assessing whether or not our 510(k)’s are good enough to even get in the front door. They issued the final guidance in December of 2012 and we’ve now had a year to see how this works, the idea being that better-quality 510(k)’s coming in would lead to faster review times, etc., and all of us have read a report or a blog or an article or two about FDA complaining that the 510(k)’s they get are not of good quality and woe is FDA because they just can’t do our reviews any faster and get us our devices cleared because our submissions are just so bad. So they came up with the refuse to accept policy. The idea at FDA was they want to focus their resources on reviewing really good submissions, not crummy ones, enhance the consistency of their acceptance criteria, and they reported this policy to be about assessing the completeness of our submissions, not the quality of the submission, so…and then they would get back to us in 15 days.

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What have we seen so far? So, there should be a difference, right, between an administrative and a substantive review? RTA is intended to be an administrative review. So is it a device? They have some preliminary questions, you can go to their website and there’s a laundry list of them, but they’re going to look at it and say, “Well, is your widget, even a device, does it belong here? Did you pay your fees? Is the 510(k) [00:01:50] ready for submission? Maybe you don’t need a 510(k) or maybe you should have a PMA. Are you even in the right space?” And then their presence or absence are required components, right? There should be a checklist. Do they have their user fee documentation? Do they have their DCs? Do they have their device subscription, etc.? Resulting in a refuse to accept or a move on to substantive review. It should be pretty straightforward.

Substantive review, we expect it’s going to be our review of the 510(k)’s. It’s the quality of your components, whether or not you have substantial equivalence, going to the AI request and response, the cycle and process that we’re all used to with the review of 510(k)’s, and this should result in a binding determination of substantial equivalence or a failure of that and you move on from there. Marjorie Shulman actually said that, “There will be no evaluation of the adequacy of contents or rationale as part of RTA.” So, what did we get?

So, here’s the RTA checklist, I don’t know if any of you have seen this. It is enormous, it has multipart questions, there are separate sections for different pieces, and it is anything but administrative. If you look through it, there is definitely a blurred line between that administrative or substantive review, and so we’re going to talk a little bit about what happened when this was implemented by FDA over this past year.

So in 2013 FDA received 2965 510(k)’s. They accepted through RTA. This is not substantial equivalence determination. This is just getting past RTA, only 1197 of them. Fifty-eight percent of the 510(k)’s that showed up at FDA’s door were turned back under the RTA guidance based on the checklist that they have. So, what happened? Some of the anecdotes that we’ve seen, there are blogs, you can Google this, FDA Law Blog had a fantastic review kind of looking back, if you will, and there were any number of reasons that kind of baffle the imagination with regard to why these were turned away including failure to indicate whether a vinyl glove had software and had passed the electrical safety standards. There were substantive questions too regarding shelf life. They also turned them away for misprints, pagination problems. I think one of the anecdotes I heard was there were two page 17s and so they turned it away. “It wasn’t good enough, go back, send it to us again.” Failure to state whether a condom was patient contacting. So, just little things like this that kind of baffle us in terms of is this really what RTA should be about?

Real quick, I’m going to actually turn it over to Rob, who’s going to share with you some anecdotes based on his experience filing submissions, and then Jorge is going to talk to you a little about what this failure of RTA, if you will, means for your new product development cycle, and then Rob has some really great suggestions for getting through it. So, Rob, do you want to tell us some of your worst stories in this regard?

Rob Packard: Yes, thank you. I work with several different clients right now, I’m working on some 510(k)’s for those clients, and when you put together a submission for the client and they’re reviewing the records before it gets submitted I get these kinds of questions. They can’t believe that we need to be this detailed, and oftentimes they’ve done a 510(k) submission themselves before and they’re looking at my submission versus the one that they prepared before on the predicate device and they’re saying, “Why do we have so much more detail? We didn’t have to do this before. Why do we need this?” Or I’m asking for information for a certain section and they say, “Well, why? I didn’t need to provide this information before,” and it’s simply because that’s the level of detail that this RTA checklist is requiring. That’s the level of detail that the FDA is scrutinizing submissions. They’re not asking questions about safety and efficacy. They’re asking you to dot your i’s, cross your t’s, and then do it 10 more times, and then it’ll be almost good enough to be rejected.

So, it’s a ridiculous hurdle that they’re asking companies to go through and it’s not meant to be, “Is your submission complete?” This is not an administrative process. This is clearly blurring the ones between an administrative review and a substantive review. But that doesn’t mean you’re going to stop submitting 510(k)’s because you’re not going to stop making new product innovations. And some of these submissions that companies are submitting are special 510(k)’s case, which is just a catch-up saying, “You know, we’ve made these minor modifications over time, we want to catch up,” or the FDA is telling you, “You shall catch up and tell us what changes you’ve made since the last 510(k).” And so it should be shorter, it should only tell you what the differences are, yet we’re still getting really tough questions about things that make no sense, things that shouldn’t even be applicable but they want us to connect the dots anyway.

So when I get these kinds of questions, you need to understand, the FDA 510(k) submission process is nothing like it was in 2003, 2004, even up through 2007. You might be able to figure out what political trigger might have caused all this, but I’m not sure a change the other direction will make it any better. I think the new FDA’s 510(k) process is here to stay and it’s only going to get worse, not better, because the FDA really doesn’t like the 510(k) process. Back to you.

Carrie Kuehn: Jorge?

Jorge Ochoa: Okay, while we turn this on, sorry to be the buzzkill of the day, but who here has been involved with the RTA process in the last year? Okay, who here is in direct charge or participation in new product development? Okay, so I want to talk a little bit about resources.

Carrie Kuehn: I could make that work…

Jorge Ochoa: Okey-dokey.

Carrie Kuehn: There you g
o.

Jorge Ochoa: So everybody should be familiar with this particular…at least this is my version, [00:08:54] version in the new product development [00:08:56], and the reason I brought his up is because we’re always thinking about people, process and product, and the standard of reasonableness went a little bit out the window with RTA, and we’ll talk a little bit about why aside from the politics.

So, Ms. Shulman…Dr. Shulman talked about this to the FDLI at the FDLI conference last year and this is what the FDA saw. So, politics aside, this is the data the FDA saw. They looked back in industry for about 10 years and what they saw is there was an increase in the average number of review cycles, that as far as they were concerned industry was getting worse and worse because they had to intervene more and more in these review cycles. Number two, our reaction time slowed down. So if we got 180 days and 179.5 days, we would come back. So, obviously, it was industry’s fault that innovation was slowed down. The third is that over 80% of the AI letters, when the FDA called up and said or sent you a letter saying, “We need more information. There were inconsistencies in the submission or they were missing some of the admin requirements.” So that’s a pretty big number and it was leveraged to justify this initiative.

And the last thing is there was actually an old RTA checklist. Did anybody know that? Did anybody know it existed, anybody in this room? That’s what I thought. Nobody ever used it. So, we took the baby, the bathwater, threw it out, and started on this process, and it’s actually unfair to put it all on the FDA because we are partially responsible as industry. What is the number one bitching point about the FDA? It takes forever, right? Well, we asked for it. Within 15 days, we’re going to tell you whether we’re going to look at your 510(k) or not. So that’s like your mom when you come in and you tell a lie, “Okay, this is what I’m going to do to you.” So, we participated in that and this is what we got.

So, the reason that the FDA gave is they wanted to reduce a number of review cycles and the total time before devices were cleared. What it means to us in industry is you get one shot at it. Once it gets rejected, clock starts again and you have to come back and there’s another 15 days. The new checklist, this was the criteria, and I’m going to tell you what I think it means to us in industry. It was meant to be a compilation of regulations, of statuses, statutes, guidance, review, everything under the sun, and what ended up happening, instead of finding the efficient intersection of all that data that needs to be put in for an initial review, what we ended up was that slide that Carrie gave us with multipage, multi-question, multipart questions, compound questions that are actually, if you remember logic from your senior year in high school, it was a union not an intersection. So that’s where we landed, and it’s much easier to form a union logically than an intersection. To do an intersection, you actually have to do a little discerning work.

They wanted to create an objective tool to understand the components and if you have a complete 510(k). Couple of things here. What they’re saying with this in my thought process, it’s important to us so it better be important to you. The danger here is who defines what objective is. Is it objective? Who gets to define it? And the FDA does. So there’s very little wiggle room. The last thing, as we stated before, is they’re supposed to be only evaluating the presence of an item, not the adequacy, in principle, so mostly administrative.

The last thing the FDA stated is, “We want to make efficient use of our resources,” which the semi-cynical view that I have is it’s more work on our part. If we do more work, they could become more efficient. So it’s a shifting of the resources, especially early on. It’s much high risk, much shorter time. When you have lesser resources at the FDA, efficiency, looking at a boatload of data with a short amount of time upfront, very high risk, we need to put that into our new product commercialization process. That’s the bottom line.

Is this making sense to everybody? It’s not a free ride. This can have a true impact in how you get your products to market. So how is your new product development process and your projects affected? Well, number one, timing, schedule, budget, resources. If you get rejected, if you get the RTA ding, clock resets to zero and you start again. At the bottom where I said the effect could be cumulative, that’s what I’m talking about. Number two, it’s not an interactive process. What we bought ourselves in those first 15 days is we send our stuff in, stuff comes out, done, we don’t get a chance. So because we were yapping off about, “Oh, we want quick, we want upfront, we want decisions,” that’s part of what we got. No interaction. There’s no limit of the number of RTA cycles, and that to me I think is one of the most dangerous things. It hasn’t come to fruition, we just need to monitor it, but 15 days at a time plus the time in between to react can add up pretty quickly, if you are on a very short timeframe as far as your product development cycle, if you are in hips, knees, spine, where new products, really significant products get launched every five to 10 years, not as big a deal, three- or four-year projects. If you’re doing stents, if you’re doing pacemakers where the technology changes every six months, two or three cycles, it’s 20% of your product development cycle. So it is significant.

Next one is the concept of substantive interaction and the MDD decision. These are actually pretty cool and I wanted to put them in here to show that it’s actually not just a one-way street, is there is now a decision point where the FDA will tell you if this is going to require [00:15:06] exercise with your submissions and require more interaction than usual, and in principle they’re open to actually reversing the first 15 days where there’s no interaction and really getting into the weeds with you, which I think potentially is a favorable thing.

The last one is—and I think they actually did hear us—remember after 90 days they’d stopped the clock and didn’t come into a decision, kicked it out and then you have to start all over again? There’s actually a tool now, the MDUFA decision where if they don’t think they’re going to come to a decision in the 90 days, they tell you and you can continue to work on it without restarting the clock, which I think that actually is a silver lining in this whole process.

The last couple of things I’m going to talk about or the last thing is, even though there’s not a lot of interaction at the beginning, we can create the interaction by talking to the reviewer because now there’s a very specific point where the lead reviewer is going to be identified and then sent to you and be part of the process. So, especially in the tail end, if they’re substantial, is there going to be substantial interaction or you’re going to pass the 90-day and there’s going to be a lot of back and forth with the FDA, and I think this has the potential to be very good, is please make your 510(k) an integral part of your new product realization, new product commercialization, new product introduction process. Anybody here that can give me a sense on whether, when you’re looking at your design control, new product commercialization, PMO office, is 510(k) part of it and is it consistent throughout? Is it addressed at all your design reviews and is it addressed by the team? Because it’s important for the whole team to be involved now because the FDA is looking at all the elements early now.

Anybody here have that inside their companies? Okay, cool. We should. Just a little thought.

Second one: Make sure, and this is something that is…this could be a very useful unintended consequenc
e of this change, is in the traditional model, even in cross-disciplinary teams, people take care of their own element and there are very few things that everybody participates in, and I think that are two elements that are highly underrated by not having participation of multiple experts in multiple fields. One is regulatory submission and number two is intellectual property protection. Those are two areas that are multi-disciplinary, nobody in any company could be an expert on everything that goes into those two areas, and those are the two areas that are most, in my experience, securely guarded by the 510s.

Patents, legal, and regulatory. Train everybody to understand that we work in a regulated environment, how important it is to participate, and that what everybody does especially now in the first 15 days, it’s critical to success, [00:18:09] dimension of success. And the last one is, even more important now, make sure that you train the people that interact with the FDA directly—and that doesn’t just mean your regulatory person on the team, but it means anybody because there will be questions especially when there’s a lot of interaction towards the end of the project—make sure that everybody speaks the language and make sure that people have great communications skills. In my opinion, you don’t only have to be very good technically and know the regulations, but the people that are great communicators are the people that are most successful dealing with the FDA. And I don’t think that all of us have 20 years of time to weed out who the best people are to do that. I think this should be a proactive…it’s a cost on your resources but it’s important.

So, just a little view from the industrial perspective, where this could go. It can affect your resources, it can affect your schedules, it can affect your effectiveness, but it doesn’t mean that’s it all doom and gloom. Rob?

Rob Packard: So, for those of you that aren’t intimately familiar with the 510(k) requirements, there are 20 sections to the contents of a 510(k). They even provide a guidance document that lists the 20 sections and explains what’s supposed to be in each section. So, we’ve provided a graph here and Carrie has done the bulk of the work; I just gave them numbers and rankings. But the top of the list there in the red, they are the two sections that are most likely to result in an RTA. We don’t have the FDA data to back this up. That would be nice to have, but they won’t give us everybody’s 510(k). I don’t know why. And then the second category is sort of the medium risk. These are the areas where you might get an RTA for something in those sections. And then the green section is unlikely, and primarily it’s because the green section consists of forms that you’re going to fill out and it’s much more administrative, so there’s not subjectivity in the eyes of the reviewer or in how you fill things out or provide information. But in the top section in particular, the FDA is asking for a lot more detail than they have in the past. But if your company hasn’t done a 510(k) in a while or you have somebody that doesn’t have a lot of experience, those yellow areas can be problems, and the next slide is a good example of that.

Volume nine, declaration of conformity. Here is a section that’s at the bottom I think of the first page or close to it of the RTA checklist, and they’re just asking you, “Have you completed the FDA Form 3654?” Well, as the name of the form would suggest, it’s kind of boring. All it is is a form where you explain, did you comply with a standard the FDA recognizes or did you deviate from it and if you did, explain how. Well, it’s a long form. You have to submit a separate form for every single standard the FDA recognizes, and just like I was saying earlier, the FDA surprises us with how much detail they want. If somebody submitted a lab report for testing and they referenced one of those standards, so it’s only a single mention buried in page 47 of a 200-page report. If you don’t fill out that form, you’re going to get an RTA letter. That’s how easy it is to get an RTA letter. Somebody else’s test report that you didn’t go through with a fine-tooth comb has a reference to a recognized standard so you need to include this form filled out for the FDA.

Another example of a real RTA letter that a client of mine got back, they filled out this form for a whole bunch of different standards but they didn’t fill it out for the ones that were obviously not applicable. So, for instance, if you have a list of standards and some of them are for, let’s say, a wheelchair that is for somebody that can move the wheelchair themselves and another standard is for a wheelchair that is electrically powered, they want to know why you didn’t apply the one that’s for the manual wheelchair for the powered wheelchair submission.

This sort of goes back to the same kind of comments we saw earlier for the condoms that they want to know whether it’s patient contacting. It’s silly obvious questions. We think it’s obvious; the FDA says “No, you need to specify.” They are also saying, “You need to fill up this form.” So here’s a lot of labor that you’re going to put into something that’s absolutely pointless and adds no value, but the FDA says you shall, so you will.

The next slide. Volume 12, the substantial equivalence. This is one of those red items at the top of the pyramid. This is probably the most technically challenging part of a 510(k) submission and it’s the whole reason why the 510(k) process exists. If you are going to submit a 510(k), you have to explain how it’s equivalent to some other device that’s already on the market under a 510(k) or something that existed prior to the FDA amendment. So, it’s a pre-amendment device. It’s something that’s been around a long time, really safe, great track record.

Well, let’s see. If I have a knee implant that was made out of wood back in the seventies or sixties and I have something made out of a titanium alloy now that has all kinds of coatings and special vitamin E added to it, those are exactly the same, right? Everybody wants that same 1970s technology in their knee. So, you can’t even keep a straight face when you say these are absolutely the same. I like to use the explanation of, “Here is the marketing department over here saying how this clinical data shows how everything is totally different from the competitor’s product and the regulatory person of the same company saying how this product is totally identical to the existing product on the market.” Now, if this seems a little bit bipolar for a company, it is, but the FDA says, “Please provide us a tabular document that explains point by point how it’s equivalent or not worse than the predicate device.”

Next slide. So, identifying a predicate, this is probably the first thing that every company ought to be doing. And you might think, “Well, of course I’m going to pick the last device I submitted because we just made a minor change to it.” Let’s say the previous version was hydraulically powered and this new one is going to be electrically powered. So all I did is change the power and, well, I added on a couple of extra features, so I guess I need to do a 510(k) submission. I can’t just do a letter to file saying, “You know, it doesn’t require a 510(k),” but in fact, when you do the analysis of what it’s going to look like on substantial equivalence table, you may realize that your competitor’s product that already is electrically powered is the better choice for predicate. So there’s a lot of strategy that’s involved in selecting your predicate device and you have to be intimately familiar with all the competitor products and how they establish their device was acceptable from a risk and safety and efficacy standpoint, and then you have to make that argument in a tabular form that some FDA administrative clerk that ha
s been there three months is going to understand. So, just picking your existing predicate device may not be your best strategy.

Next one. In volume 11, this is the one that’s going to look about 10 times thicker than you’ve ever seen before. Each of these slides, I have like part B on here, this is part B of the RTA checklist and it’s fairly lengthy. They’re asking for a lot more detail in what will be the device description than you’ve ever seen before, and things that you didn’t think were important they want to know about.

Next slide. And here is the other parts of the RTA checklist, and as we said before it’s a fairly long document. It has parts A through K. And I’ve indicated a couple of points here that might jump out and grab you, like, “Is your labeling device specific? Is there a guidance document that the FDA has for that type of device?” That’s important because they may say, “You shall have a label that includes the following information.” The newer guidance documents that the FDA is issuing now actually do. If you have sterilization, you may think, “Well, I’m going to reference the gamma sterilization or the EO sterilization standard.” Well, if you do anything that’s a little bit out of the ordinary, you could dump yourself into a third guidance document that’s out there or a standard for nontraditional sterilization validation. So the FDA is getting tougher and tougher all the time. Every single time somebody has a recall, the FDA looks for what more regulations can we throw at them. So it won’t get easier, there’s no good hope in sight, but the best thing you can do is try to learn this process really, really well and, as Jorge indicated, train your whole organization because one person cannot possibly do it all. It’s a team effort to get one of these across the finish line. I think that’s it.

Carrie Kuehn: Yeah, I think that’s it. So just to wrap up, I think that the message here is that RTA is not going anywhere, so we need to find a way to, within our processes, within our organizations, accommodate it, cope with it, and try and work our way through it. The hope would be that that acceptance rate goes up, but I think that remains to be seen and, clearly, the line between an administrative refuse to accept review and a substantive review has not been drawn very clearly at FDA, and so it behooves us to do our best to make sure that our submissions are going in.

I think the anecdotes indicate that our submissions aren’t as bad as maybe the failure rate would indicate. It’s that the decisions being made are not necessarily logical or meaningful. One anecdote that recently I read about was that the submission went in, they got an RTA, worked with the reviewer, got the concerns that the reviewer had brought up addressed, sent it back in and got another RTA because the first reviewer was now gone and they got a new reviewer and all the questions had changed. So, I think there are still a lot of challenges I’m hearing. We’d love to hear your stories and answer your questions. Thank you.

Joe Hage: I have to laugh. Jorge in the middle of the presentation said, “I hate to be a buzzkill.” The whole damn presentation was a buzzkill.

Carrie Kuehn: [Laughs] There is hope.

Jorge Ochoa: Drinks at six, man.

Joe Hage: It’s drinks at six. That’s why they sponsored.

Carrie Kuehn: That’s right. That’s why we gave you the drink tickets.

Joe Hage: Okay, our first question is from Brian.

Brian Blachly: Hello. We import blood pressure monitors and they’ve all been complied with by FDA except for one part of our hospital monitor, which is SpO2. We sent that in 6 months ago, we’ve heard nothing. Is that good or bad?

Carrie Kuehn: Sent in your 510(k) six months ago?

Brian Blachly: 510(k), yes.

Carrie Kuehn: So you got past RTA, it went for substantive review, and you have not heard back or…?

Brian Blachly: We’ve heard nothing. We thought we’d have an answer a month ago.

Carrie Kuehn: I would call your reviewer as soon as possible.

Jorge Ochoa: They’re supposed to get back to you within 15 days.

Brian Blachly: Thank you.

Carrie Kuehn: Yeah, so do you know for sure they got it? Because that would be my first question is, did they indicate that they actually received it? Because you should get a letter that says that they got it.

Brian Blachly: That’s not my department. That’s my partner’s department.

Jorge Ochoa: Everybody needs to be trained.

Carrie Kuehn: So, about the training…

Joe Hage: You were saying something about the entire organization, right?

Carrie Kuehn: Let us know if we can help you though.

Rob Packard: The same comments apply to not just 510(k)’s but any interaction with a regulatory body. It doesn’t matter who it is. Do not wait for them to call you. Do not wait for them to email you. If you think they’re going to call you on Thursday, call them on Wednesday. Be polite about it, be professional about it, but don’t wait for them because they are administrative. They have a very heavy workload and they will forget, things get lost, and it’s your fault.

Carrie Kuehn: Yeah, one of the things I would say just to respond to that as well is a lot of the folks that I talk to are actually afraid to call FDA. I can assure you there are some really nice people there. They’re a hardworking people but they don’t always make good decisions as we’ve seen, but you should never be afraid to give them a call and say, “Hey, what’s going on?” They’re not going to show up and inspect you the next day just because you called and said, “Hi, I’m over here,” which I have actually heard people afraid to call FDA because they’re afraid that means they’ll get inspected.

Rob Packard: That’s the IRS. [Laughs]

Carrie Kuehn: So, as Rob said and as he said, that goes with any agency. Don’t be afraid to pick up the phone or get someone like Rob or me or whoever to call them for you and find out what’s going on on your behalf.

Ross Bundy: Hi, we just started our submissions and actually we haven’t done…we will do a 510(k) but right now we just submitted for our pre-submission meeting, and so how useful is that meeting in terms of passing something like RTA and are the folks there that we’ll talk to? Are they well-versed in RTA issues and maybe give some advice in terms of how to pass it?

Rob Packard: The quick answer is it depends. If it is a device that has a predicate that’s obvious and there’s a very similar product on the market, it’s a waste of your time and money. To give you an example, if you go through the 513(g) submission process, which I gave a link for up there, you’re going to wait 60 days for an answer, you’re going to pay a few grand for it, it’s going to be nonbinding, and it’ll probably be wrong. That’s the good news. [Laughs] However, if you have a device that’s totally different and you’re having a lot of trouble identifying a predicate device, and when you call up a consultant they scratch their head several times, you probably need the pre-submission process. I don’t think the 513(g) process is going to be much good to you, but you probably need to still talk to the FDA because you may be headed down the road of a De Novo submission and you’re trying to avoid a PMA,
and you probably don’t want to do this without a lot of coaching and preparation in advance.

Carrie Kuehn: Yeah, I would agree with that. I would follow up with you can still interact with the FDA without going through the pre-submission process. So you can talk to a reviewer in your reviewing branch and get some questions answered, and then you don’t have to go through that. That may answer your questions.

Ross Bundy: They actually advised that we go through [00:34:15].

Carrie Kuehn: If they advise you to do it, then I would do it, yeah. Yeah. Whether or not that’s going to help you with RTA I think is questionable. I don’t think we know the answer to that yet. I think it depends on whether or not the reviewer that would be handling your RTA and your submission is going to be in your pre-submission meeting and I don’t think there’s any guarantee that that’s the case.

Jorge Ochoa: That’s the good and the bad of it. The RTA is much more dependent on the lead reviewer or the individual reviewer. The 513 process is really good for more overall, put your finger in the pool, see what the temperature is. That’s really good for you. If you need that, if you’re in that kind of gray space of technology, then it’s worth something.

Carrie Kuehn: I would also remember what Rob said, and that is that anything in those pre-submission meetings is nonbinding. So don’t be surprised if they come back and say, “Oh, you know what, actually, we’d like to get this additional information.” One of the ways you can avoid that kind of ambiguity is to go into your pre-submission meeting highly prepared with a very specific list of questions. What I usually tell clients is don’t ask FDA how to do it. Tell them how you’re going to do it and see if that’s okay. It’s usually going to be more beneficial and productive that way.

Jorge Ochoa: It’s like going to Vegas. [Laughs]

Joe Hage: Our next question comes from my friend Debbie Black. She’s flown all the way here from Australia.

Carrie Kuehn: Can I fly back with you?

Jorge Ochoa: Drinks at six. Yes.

Joe Hage: I don’t know what her question is yet but give her a nice answer, would you please.

Debbie Black: Okay. I’m from Bionic Products and we manufacture a negative ionizer of oxygen which we export globally, 50-year-old company, and we’ve had TGA approval in Australia for quite a few years. I’m just about to go down the process of the De Novo 510(k) that I learned about yesterday with the FDA and I actually have an appointment with you, Robert, next week, but you probably don’t know that yet. [Laughs]

Carrie Kuehn: Yes, they know.

Debbie Black: But what my question relates to is our particular medical device, we had to fight in the Supreme Court for eight years to prove that we can make the medical claims that we are making in Australia, and it got us to the point where we are the only one registered in Australia and TGA has told us they will not register anybody else, plus we have global patents protecting our science anyway. But, from my discussions so far with the FDA, my intended purposes that I’m allowed to say in Australia I would not be allowed to say in the United States. Well, that actually presents a huge problem because with my websites and international websites, how can we communicate to the consumer in a language that they can understand what our device can do if we have to try and fit within different jurisdictions globally when the Internet goes across so many different regions? I don’t know how to fix this issue.

Carrie Kuehn: Rob will give you some really good advice next week, but it’s a huge labeling problem. And so the key is I think going to be to work with the FDA to generate a web presence that is US-specific. I mean, other companies have had this concern. There are indications overseas, for example, in hips, for example, [00:37:59] resurfacing, it’s cleared overseas and it’s not cleared in the US, things like that. So I think it’s a matter of working with…it’s a labeling and marketing issue that you’re going to have to create one that’s very specific to the US, and then on your other OUS web presence it’s going to need to be very clear that the indications that you’re describing are not cleared in the US. And so it’s a challenge. It’s certainly very complex. Rob, you want to…?

Rob Packard: The only thing I would really add to that without getting into specifics that we don’t have time for would be that your distributors also need to follow you. So, one of the ways to irritate the FDA severely is to sign up a bunch of distributors that create their own websites and do their own thing because you’re the legal manufacturer that’s on the label and you’re the one that’s going to get in trouble with the FDA, not the guy that’s just shipping it.

Joe Hage: Our next question comes from Dick DeRisio. He is with notified body TUV SUD, also one our sponsors, and I’m interested to hear what you have to say.

Dick DeRisio: My comment comes from many years of living the dream doing 510(k)’s and PMAs, and just to reinforce something that Jorge said about getting the right people with the right expertise, since a lot of people here are involved with new product development, often what would happen is the R&D group would keep regulatory out of it until the very end, until they started throwing all the reports to them, and I ran QARA for many years in companies. The fact is they miss the sizzle of going to clinical advisory boards, meeting with the key opinion leaders who are talking about the new technologies, and they never had a chance to get excited and find out why they could support the indications and claims. So whether it’s a quality engineer or a regulatory manager or specialist, having them involved at the earliest stages really gets them excited and makes them much more conversant with FDA in terms of the values of that device.

Carrie Kuehn: Yeah, actually, one of the things we wanted to do at 10x and there just wasn’t enough warm bodies to do it but it’s still something that we want to promote, and that is what we call kind of your blue-collar regulatory—it’s kind of our term for it—and that is training your operations and manufacturing and quality people to understand their role in the regulatory process whether it’s submissions or compliance. We’re not trying to train everybody to be a regulatory specialist. Not everyone likes to read the CFRs at bedtime like Rob does, and I wouldn’t know anything about. But having a basic understanding of their role in the quality system, in their role of generating those reports for your submissions so that you can get past RTA, just having a general sense of it, can change how they think about the work that they do and lead to better overall compliance both from a quality system perspective but also lead to greater efficiency. So I think it’s a really good point, is that regulatory shouldn’t be relegated to the regulatory space only, it should be pervasive throughout your organization.

Jorge Ochoa: If you have a guy or a lady at the end writing a 510(k), RTA City, absolutely.

Rob Packard: I wanted to add one more point. I like your comments about getting regulatory involved early, but I actually started out in R&D, so the last thing I did in my career was quality and regulatory and I think that’s benefitted me tremendously because I can walk into design meetings and I speak their language, I think their way, I’ve done their job, and I can help t
hem do what they’re doing as well as teach them what I do. But I know that regulatory pathways and regulatory strategy is not all that exciting to the R&D team, but when I can give them a list step-by-step of “these are the tasks that you’re going to have to do for verification and validation, and I can guarantee you it’s 100% of the list, I won’t add on more later,” that’s really helpful to them. It’s their yellow brick road. All they got to do is stay the path and do those tasks, and if I can give it to them before they’ve decided what the design solution’s going to be, whether it’s going to be battery-powered or line-powered into the wall, that’s extremely valuable to them because they can say, “Well, which solution will be easier to pass that test?” because I already told them the tasks. And so I’ve actually had several R&D people say, “This is fantastic. I’ve never had one this good before.” Well, that’s because you asked for it a week before you want to submit. It’s not a checkbox in your technical file or your DHF. It’s something that’s supposed to help you plan your whole entire design project, so if you don’t do it early enough it doesn’t have much value.

Joe Hage: The good news for all of you and those of you watching is Rob is really good at what he does. He leads our QARA subgroup, which in my view is our best subgroup for the entire group. He pours himself into it every week and writes something really, really meaningful, so all that goodness means he’s really really busy. The bad news is I don’t get to hang out with my friend on Skype so often anymore. So, Vizma, you had a question.

Vizma Carver: Sure. Hi, and I just spent a year inside FDA as an industry expert as part of their entrepreneur and residence program, and yes those challenges are there. There’s also an interesting dynamic of when we were starting to just pitch some of the ideas in the [00:43:47] pre- and post re-balance, which was one of the cohorts I lead, and it was interesting to see how much pushback came from industry to not change it, because they use FDA as their legal buffer of once it’s approved by FDA we have less legal cases against us. So just to put a little bit of one of the reasons FDA keeps having all of those “more data, more data” is that they’re the ones that are dragged down in front of congress, not everyone behind the scenes, and industry then wants to continue to use them. So just giving that perspective as they’re making these regulatory changes and these guidances that are coming out as part of that strategic plan that we helped them make for this year – that’s also behind the scenes.

Carrie Kuehn: Yeah, I think when it comes to doing a 510(k) versus a PMA we’d all prefer the 510(k), please, because you don’t have time to clinical trial. I will say as someone who works with clients in adversarial situations where they’re either being sued or they’re in other adversarial situations that getting your device cleared by FDA does not really give you a whole lot of buffer against liability or litigation. PMAs, you get to deal with the…you get a little more protection under preemption, but with the 510(k), getting your device cleared, it rarely provides much of a speed bump. So, I think while that might be some motivation for industry pushback, I think that the greater motivation, and this is just my personal opinion, is given the choice of doing a clinical trial and spending that time and money and burn rate versus a 510(k), the 510(k) as much of a pain as it is and as much of RTA is a speed bump now, again, it’s still a more timely and more efficient pathway to market. So, I think there are a number of reasons for that pushback.

Joe Hage: Rob, you told the story about how the bipolar organization has a marketer saying, “Brand new, fantastic,” and regulatory saying, “It’s completely like the other thing.” Ed Black is, as you know, on our medical devices group advisory board and he’s my go-to for matters relating to reimbursement and health economics. And he participated in a workshop yesterday where he showed two triangles, one of them pointing up, one of them pointing down, and he was making a comparison of the things you need for FDA and the things you need for CMS, and I wondered if I could ask Ed to comment on the presentation and what challenges and what possible solutions. You know, finish us off here with some good news. [Laughs]

Ed Black: The fun of my job is telling entrepreneurs their new technology won’t get paid. That’s what people like I get paid to do sometimes. The comment I made, and Doug Limbach was here, it came up I think in the course of talking about the difference between patent protection, working with a patent office, working with the FDA, and working with the CMS, is that there are predicate devices that help you get through FDA clearance. That can hurt you when you try to get intellectual property patents that get even more confusing when you describe them differently to CMS, and you have to be careful when you talk to three federal agencies who all don’t necessarily talk to you until you leave an audit trail that could come back to bite you.

And the other thought was that regarding the triangles I show is that the FDA and all the work that you do to get a product clinically approved is focused on isolating all the other variables outside of an equation to demonstrate that your technology does exactly what it’s designed to do so you can meet that requirement for being safe and effective. But, when you take that technology into the real world and health plan medical directors look at that and try to figure out what that’s going to mean to the populations they cover, they look at this from a completely different perspective, and they know that when you take your clinical trials to the best university medical centers and the best surgeons and others, they aren’t the ones who are going to be using the equipment once they approve for coverage within their service areas. So there’s a completely different view of the world when it comes to covering something because not everything that is safe and effective, which is the mantra of FDA, is reasonable and necessary for treating any particular medical condition, which is the harbinger of Medicare and third-party payor coverage. They’re the left and the right arms of the federal government. They just look at the world much differently.

Carrie Kuehn: Yes, great points.

Joe Hage: Anything to add to that? Doug, did you want to add a comment? Okay. Well, in that case, I have some good news for everybody. It’s lunch time. And before we go, I’d like to thank my friends Jorge Ochoa, Carry Kuehn, and Rob Packard. Thank you.