Kristen Mittal, Co-founder and CEO of Mittal Consulting

Jesus Moreno (00:01.772)
Welcome back to Global Trials Accelerators, the podcast where we dismantled the barriers to clinical innovation and explore the strategies driving the next generation of life-saving therapies. I'm your host, Jesus Moreno, and today we're discussing the famous Valley of Death. It is a dramatic term, yes, but it's actually an accurate description of the brutal reality for most medical startups. In this space,

The Valley of Death isn't just about a lack of funding, but it's a race against the regulatory clock. Every day spent waiting for a domestic trial to be approved is another day of capital burn that many young companies simply cannot afford. However, there is a strategic side door conducting clinical trials outside the U.S. to gather high quality and fast data. However,

The critical question is, will the FDA accept it? Does this move actually save the company or does it just delay the inevitable? Joining us today is Kristen Mittal, co-founder of and CEO of Mittle Consulting. With a background in biomedical engineering and a dual RAC and PMP certification, Kristen has gained

CS1 or class 1, 2 and 3 device ranging from AI to orthopedics through a gauntlet of regulatory and commercial. Excuse me, let me start that that part again. Joining us today is Kristen Mittal, co-founder and CEO of METAL Consulting with a background in biomedical engineering and a dual RAC

and PMP certification, Kristen has guided class one, two, and three devices ranging from AI to orthopedics through the gauntlet of regulatory and commercial affairs. She is a mentor across West Coast incubators and specialists in helping startups align their regulatory strategy with their reimbursement and exit goals. Kristen, it's great to have you.

Jesus Moreno (02:27.49)
here with us navigating this waters. Welcome to the show.

Kristen Mittal (02:31.958)
Hi, Jesus. Thanks so much for having me on. Really excited to have a conversation with you today.

Jesus Moreno (02:38.104)
So am I. Kristen, your background is deeply technical. Understanding... Excuse me. Let me take a sip of water. I think that's part of it.

Jesus Moreno (02:59.208)
Kristen, your background is deeply technical and your undergrad and master degree in biomedical engineering. Usually someone that goes so deep into the STEM area, spends their career in research labs and product design, but you chose to walk a different path. Can you tell us about your earlier years?

And when you realize that you didn't just want to build a device, but rather solve the complex puzzle of getting them through the regulatory gateway and into the hands of doctors and patients.

Kristen Mittal (03:39.256)
Yeah, great question. I think I was very lucky when I was going to school with my undergraduate and graduate degrees. While I was there, I was able to do internships at different startup and small medical device companies and really got an understanding of different career paths outside of research. I mean, through my education, I had no idea about regulatory affairs. I didn't know it existed.

I was actually doing an internship at a very small medical device company when I was in college. I was helping them with their quality affairs work. at some point we got finished with the quality affairs and they said, well, we have an audit coming up, an ISO and FDA audit. Can you help us with that? And I said, sure, why not? We'll try it out. And from preparing for that audit and then going through it, was...

a wonderful experience and I say it's not right for everyone, but it was for me love at first sight and I have been on that path ever since. I think there's something really special about being able to go through all the complex documentation and being able to distill it down into something so simple and tell a simple story out of something that can be very complex. And that's why I enjoyed that position then and still

Love helping our companies from that perspective up until today.

Jesus Moreno (05:09.725)
Wonderful. And I agree, it's not for everybody, but it's so important in that initial stage of developing that there's a wise counsel that knows how to navigate this waters. that I think, and I would love to hear your thoughts on it, really makes or breaks the future of a company. And you've worked with

everyone from university incubators to established manufacturers. When you walk into a startup that just has a prototype and a dream, what is the most common regulatory blind spot you see in their five-year plan?

Kristen Mittal (05:52.162)
Yeah, so at Mitol Consulting, we exclusively work with startup medical device manufacturers who are on the novel or complex side. So we're working through really complicated regulatory strategies to be able to successfully get to the market. you know, the biggest challenge for these first time founders is that they're first time founders, so that there's so much they don't know, and they have so little time to get up to speed quickly.

So it's really important for them to start aligning with experts or fractional people on all of the different subject areas who really do know what they're doing and want to help them to be able to know, learn what they know and learn what they don't know and be able to get the resources to get up to speed really quickly on what they don't know.

Jesus Moreno (06:41.653)
And what do you think that is, that the regulatory aspect is a lesser known reality of building a company, building a product in at least the medical space?

Kristen Mittal (06:51.704)
Yeah. Yeah. So a lot of the first time founders we work with are, you know, professors turned for founders or entrepreneurs that were previously physicians turned founders. So they have a different lens that they're coming from a different set of background. If they were in the lab for a long time, they may really like to do clinical studies for the sake of clinical studies and the sake of furthering research.

And that's fabulous because that lays the foundation for then these companies to be able to come out and become in the startup phase. But there's a big transition from doing research for research sake and doing research to be able to support a marketing application. FDA is looking at these studies through a very scrutinous lens, which they should be because they want to make sure that the devices coming on market are going to be safe and effective.

So they're highly critical about how these studies are set up so that they can really, so a lot of times we actually have the companies work with the FDA through the pre-submission process to get them on board with how these studies are set up so that presuming we get good results that it will be accepted later down the line in a marketing application.

Jesus Moreno (08:10.293)
And what would you say is the biggest difference between doing clinical trials for the sake of advancing knowledge and for the sake of proving safety and efficiency, effectiveness?

Kristen Mittal (08:23.8)
Yeah, so things that maybe aren't always thought about is if a researcher is doing research in their own institution, it may be somewhat of a homogenous sample size in terms of patient population. It also may be homogenous in terms of the types of physicians or professionals who are using that device. So that's perhaps one aspect they don't think about when FDA really wants to make sure that this device can be used by

everyone in the US, all different types of physicians, whether it's rural or academic or urban hospitals, or, and it can be used by on all different types of patient populations. So it's not specific for one different type of demographic. That's very important to the FDA, rightfully so. And other things that they should be thinking about.

would be sample size justification, the biostatistics of it all. So trying to figure out what is the right sample size to be able to really prove certain metrics as opposed to just suggest it.

Jesus Moreno (09:34.066)
That is definitely something I would like to cover in more detail as we progress in our conversation, in particular when we broaden our discussion to other geographies and having those type of considerations when engaging sites and professionals abroad. But I would like to talk about a buzzword we hear daily, which is AI.

You've dealt with class one, two and three devices across totally different fields from neuro to ortho to even AI. And nowadays that line, I don't know if you would agree, but to my estimation, that line between software and hardware is blurring out. And how has your approach to project management to...

devising or strategizing the regulatory plan change as you keep with the speed of digital health iteration.

Kristen Mittal (10:49.614)
Yeah, so we actually help a lot of clients right now with AI submissions, whether AI, S, D, or AI with hardware and software in it as well. know, AI is a huge budge for it. And it's, think our clients are going to really game change the industry in terms of the types of products we're helping them bring to market in terms of decreasing physician fatigue and workload and all of that, and hopefully making it a better system to be able to use.

But in terms of the regulatory aspect of getting it through the FDA, I really don't think it's any different than any other type of application. AI is, you know, it still has to be controlled. It still has to have all of the frameworks in place that a normal software application would have as well. There is a higher scrutiny bar, right, because FDA wants to make sure that this is somewhat.

less known than other types of applications. So they still want to make sure it's reviewed rigorously and we have to have the right data plays. have to think about things like training sets, retraining sets, how are we accounting for bias, and all of these types of things. But it's still an application. You collect the data in a systematic way. You make sure you have rigorous data and

controls in place and then you present that to the FDA just like you would with any other application.

Jesus Moreno (12:14.825)
I see. So the rapid iterative nature of this technology doesn't make for more challenging project management, considering that the product can change drastically overnight with a few lines of code when that dependency between the hardware and the software is so tightly knit.

Kristen Mittal (12:44.6)
Yeah, so definitely companies can have AI, real true AI platforms coming to the market, but they still have to be locked when they get on the market. So it's not like they're ever changing and morphing in the background without someone having proper software verification and validation going on. So still, if you want to make changes, the best way you can do is through a PCCP with the FDA. If you have a lot of different AI software changes you want to make once you get onto market.

But nevertheless, that is a very controlled and rigorously scrutinized process to make sure that this doesn't go out of control once it gets onto the market. There's a lot of controls in place to make sure it doesn't suddenly turn into something that the company didn't expect it to be.

Jesus Moreno (13:32.012)
I see. It's good to hear that. At the speed that we're moving with AI and generative AI and agentic AI, it does raise some concerns in terms of how much is this is being controlled or led by those boundaries, safe boundaries that we've

established through the regulatory processes. And if those boundaries are able to keep up with the speed of change that these technologies have brought to the market. But, going back to that valley of death that we mentioned in the introduction, statistically, we know that nearly 90 % of medical device startups fail. And many of them die right in the

gap between the prototype and the clinical validation. From your perspective as a consultant, why is that mortality rate so high? And is it usually a lack of capital or is it a failure to respect the regulatory clock, let's say, to achieve the objectives before the funds run out?

Kristen Mittal (14:57.626)
Yeah, well that early on, could be a lot of reasons and not necessarily a regulatory reason. I mean, the biggest thing for first time founders and medical device startups is to always be raising, to be able to get enough documentation in place to convince an investor to fund their company. So then a company has to think backward, what do I need in place to really be able to convince this investor that this is the right solution? And I will say,

We can definitely get medical devices through the FDA. It's challenging, it's not gonna be the biggest challenge for our novel and complex startups actually. The biggest challenge is gonna be once we get them on the market, how are they gonna sell and who's gonna pay for them? How are they gonna sell at a volume and getting that reimbursement in place? So we do BC due diligence as well and our investors are now and more and more asking BC.

for these reimbursement assessments in addition to these regulatory assessments to really understand, yes, this may be a great idea, but does it really have a good spot in our US healthcare system? Is it really something that can either supplement, augment or replace what we already have on the market? So how does it fit in the US current standard of care? And is it worth paying for?

Are people going to want to pay for it once we get it through the FDA and on the market? So those are the even more important questions of figuring out, should we even bring this through the FDA? Is there a space for it? And also thinking about other markets, because a lot of humanitarian devices really don't have a place on the US market, but they have great places on other markets.

And so the earlier a company can really figure out what is the long-term commercialization and reimbursement strategy and which market is that most appropriate for, the less likely they're going to burn through a lot of capital going down wrong avenues and be able to really throw all the capital to the proper avenue that's going to serve them long-term. And that's a lot easier said than done. But really thinking about that focus much earlier and not saying,

Kristen Mittal (17:15.77)
Hey, I'm gonna wait till after we get through the FDA to start thinking about this, because it's challenging and complex. No, we should really be thinking about this commercialization and reimbursement strategy at the same time we're thinking about regulatory strategy.

Jesus Moreno (17:31.286)
Excellent. think that's a perfect segue to the next topics that I would like to explore with you. talking about that abroad strategy, some consider it like a lifeline, a lifesaver strategy for startups that have to go through clinical trials quick in order to, you know, be able to

compensate their burn rates. And for cash-strapped startup, what are the primary advantages besides just cost of looking outside the US and consider early-feasibility clinical trials or even pivotal trials? And how does that align with what you were just

mentioning the strategic commercial plan.

Kristen Mittal (18:29.818)
Yeah.

Yeah, so for that higher complex or higher risk devices that do require clinical trials to get on the US market, FDA's stance is more or less it needs to be the pivotal trial on a US population, at least 50%. But these trials in the US are very expensive and very time intensive. So the question is, how do our companies get funded to be able to do one of these trials? What do they need to have in place?

to be able to go to that step. And you're right, a lot of times thinking outside of the US to do these studies is a great way to do for early feasibility because you really don't know if the study is gonna go well. So if you can exercise a less time intensive or less costly option to really build up confidence internally, right? You wanna have confidence going into a large scale pivotal trial that you're going to be successful.

and build up investor confidence as well. That's a great avenue to pursue and a lot of our clients do that in order to build up everyone's confidence that the larger trial is going to be successful. That's one way to think about it. The other way to think about it is we can actually work with the FDA through the pre-submission process to get them on board for a multi-site, multi-country type of trial, even at the pivotal stage as well. It doesn't always work out, but if you start early,

communication with the FDA about it and start telling them and thinking how you want to think about this and set this up, they can work with you to be able to design a multi-country trial that they would be on board with, given that their concerns of safety and risk are all met in how the study is set up. So we've seen it work in both ways.

Jesus Moreno (20:22.381)
Okay, could you maybe outline what are the must haves to ensure that outside of U.S. data is actually, if not...

if not supporting evidence for US submission, at least an adequate approximation to that burden of proof. What is the FDA looking for in data from places like Australia, Europe, or even South America?

Kristen Mittal (21:00.238)
Yeah, they're really looking for high quality documentation. They're looking that you've followed GCP protocols. They're looking that you have really thought about sample size, patient demographic. You've really done an analysis of how the standard of care is the same or different, rationalizing the same physician types of practices as how comparing it, how it is in the US and how the patient population is compared to the US as well.

So those are things that they're looking at. They're going to very scrutinously look through all of the documentation. So making sure it's a very high quality is very buttoned up. Nothing is inaccurate. Nothing is inconsistent. Nothing is missing.

Jesus Moreno (21:45.666)
Would VCs be looking at the same features in your data set, or are they more interested in how easily the clinical team was able to use the device or the technology, the platform to perform the theoretical process?

Do you see any difference between those two perspectives, regulatory and VC interest in what they're looking for in outside US trials?

Kristen Mittal (22:24.368)
Yeah, I mean, it's going to be the same. They want to make sure that that data is going to support eventually either US trial or eventually US application. So they want to make sure it's also suggesting the same thing. It's increasing confidence and bridging that gaps of the unknown. And so they're looking at the same types of things, perhaps through a different lens.

Jesus Moreno (22:49.225)
And are there any certain therapeutic areas where an outside the US strategy is a no-brainer versus others that the regulatory bodies or just the nature of the, let's say, medical problem that we're trying to solve doesn't lend as well to those outside the US trials?

Kristen Mittal (23:20.002)
Any of this is a no brainer. think all of it has to be really thought about in terms of it. It's going to be a unique strategy for every company, depending on who they have on their team, what their funding status is, what type of product they have. So I think it's a unique decision each time. Definitely the biggest considerations when using the OUS data is if your device type is, for example,

looking at skin analysis and skin color has to be a factor. That's going to be very highly scrutinized by the FDA to make sure you're being representative of all the different types and have enough adequate representation of the different PhisPatrix scale colors. So you have to think about the unique aspects of your device, which might play into place for either the patient population

or the current standard of care or the physician representation.

Jesus Moreno (24:26.605)
And beyond that FDA regulatory, let's say, yeah, process, how does the outside the US trial strategy impact a company's exit strategy? Is it well received by the strategics? Is it a highlight? Is it something that draws away from their interest?

How do you look at that?

Kristen Mittal (25:00.706)
No, not necessarily.

Jesus Moreno (25:00.971)
the fact that they conducted them. Sorry.

Kristen Mittal (25:04.779)
Yeah, it's not necessarily a detractor at all. It's all about it builds the story, it tells the story. So it really have the question is going to be how did those results go? How did the studies that were conducted after those studies go? That's part of the evolution of the company and the story that they're building.

Jesus Moreno (25:25.407)
I see. Well, thank you. Thank you so much for talking about the side door of outside US trials and advantages and disadvantages of this strategy. But that's only half the battle. Even after crossing that valley of death and having some proof that the technology works, as you mentioned previously, surviving is only half of that.

that challenge. The other half is eventually getting the commercial strategy in place and placing the product in the hands of doctors and patients and actually have health care insurance cover the cost of those therapeutic devices. I would like to explore that a little bit further. And we often see that

There's a victory gap between companies that get their FDA clearance, but then sit on the shelf. The product sits on the shelf for two years because they don't have a reimbursement code or a commercial strategy in place. How do you coach founders to design their trials, whether inside or outside the US, so that they

don't only collect the necessary data for safety, but also collect the economic evidence, let's say, players like CMS demand when approaching a buyout.

Kristen Mittal (27:10.316)
Yeah, that's a great question. And I'm really happy you brought this up, Jesus, because we work with a lot of breakthrough clients. And they've done a study for breakthrough devices, and they've shown that it takes an additional after getting through the FDA and getting approved, it takes an additional five to seven years on average for them to be able to get reimbursement. So a lot of companies can't with stain that additional time. And they do go out of business during that time. So

That is one of our main focuses is to bring this conversation much earlier and think about how could we potentially modify our regulatory strategy or modify our clinical study to be able to take into account these different considerations. So I think one of the misconceptions is that FDA only looks at safety and efficacy when they're reviewing these applications. We don't submit any value or cost data. They're not reviewing.

from a value perspective. On the flip side, reimbursers, that's all they're looking at is value and cost and how it fits into the current standard of care. So one thing might be is if you have one widget coming out that, you know, there's five already on the market and yours is number six, you went through the 510K, it's number six, maybe it's a 30 % longer battery or some aspect of it. Now, sure.

We can get that through the FDA, but the reimbursers are going to ask, well, if I'm already paying for these other five, why would I pay for your widget? Is that 30 % longer battery life really worth it to get you in our system? Is it going to justify this price premium increase compared to the competitors? This is how the reimbursers are thinking. if we can figure out certain, also from the regulatory perspective, if we can figure out certain product codes,

that have better reimbursement rates than others and go down specific pathways or modify the indications for use statements to help them hopefully have longer term success from a commercialization perspective. That's something you want to figure out when you're in the strategy phase, not once you've already gotten on the market and have to go back and change that. Other aspects would be setting up the clinical study as opposed to just proving safety and efficacy. Can we also look at things like value and

Kristen Mittal (29:37.866)
longer clinical term aspects of decreased hospitalization. What are the other secondary endpoints we can be looking at? Because oftentimes after the company gets through the FDA, they will still have to do another clinical study to be able to show these endpoints that the reimbursers are looking for. So if we can combine these studies into one, as opposed to them having to do a second one once they get on the market, that is potentially very valuable for these companies for their longer term success.

Jesus Moreno (30:08.041)
And would you say that those reimbursers are comfortable with looking at outside the US data as a source of truth that signals that this particular product would be or has those functional advantages or cost advantages?

Kristen Mittal (30:33.464)
It really depends. It really depends on the situation. I can say at a high level though, there's a lot of clinical studies that have been done outside the US that are then repeated inside the US and don't get the same results. So FDA is acutely aware of that. So it's something that can be supplemental and also build up the case, but not necessarily a standalone type of data set.

Jesus Moreno (31:04.173)
Wow, that's very interesting that the geographical location of the study has such a bearing on the results. But shifting our perspective for a minute, you spend a lot of time with incubators and universities. If you were looking at the 2020-30 landscape, rather, what is the one future

skill MedTech founder needs to develop right now. Is it understanding AI or is it the ability to navigate increasingly fragmented global regulatory landscape?

Kristen Mittal (31:48.996)
Yeah, I think US first is usually a pathway for a lot of companies. So it's not necessarily the fragmented landscape. you consider different countries after US if US is a good market for your product type. I would say first time founders have an incredibly hard road ahead of them. I won't sugarcoat it.

because they have to either, if they want to stay as the CEO, they have to really develop good business skills and realize that they're running a business as well. So thinking about it from an entrepreneurial perspective and not just a research perspective. So we have some CEOs who can make the switch and are really good at it and get up to speed on what they need to know from a entrepreneurial perspective.

And we have some CEOs who really like the research aspect of it, and that's where they want to stay. That's what they're much more comfortable with. And so in those cases, being able to identify which type you are and being able to fill in the gaps, so perhaps putting in a CEO in place who has had that prior experience of starting and running medical device companies to really make sure that they have the right team and they're going to be successful in the long term.

It's a hard decision to have to make, but it's really important for them to make early on so that they have the right people in place to be able to support them through the long term.

Jesus Moreno (33:18.089)
Of course, well, having been on both sides of the table, both the entrepreneur side startup and the sophisticated investor, what are some of those critical signals or indicators that you've come across doing that deep dive due diligence that tell the story of

truly de-risked and ready for scale a company. And conversely, what are those quiet red flags that suggest the company has checked all the regulatory boxes but has fundamentally failed to build a survivable transition to a global stage?

Kristen Mittal (34:10.904)
Yeah, definitely. I will say for our companies that are in the startup phase, it's really important. The things that we look for in terms of what's likely going to be a high quality company is one that from the beginning has thought very hard about who's going to be part of their team. So they really do have the right expertise in all of the different areas to be able to help support them.

That's one is thinking about the right team and having them in place. Second is making sure that, yeah, I don't have a second. Maybe we can edit that out. I did have it, I forgot it.

Jesus Moreno (34:51.725)
Okay, it's okay if you want to take a minute and maybe gather your thoughts and maybe share with us a little bit of your insights of what are those strategic signals or characteristics. Okay.

Kristen Mittal (35:09.146)
yes, I remember the second one. Yes. The second one to have in place is making sure when we work in the novel and complex, so making sure from a regulatory perspective that they're doing things in the proper way. So they're engaging early and often with the FDA through the pre-submission process.

that is really the best way to de-risk their regulatory pathway. So getting the FDA on board early and often on what they're doing and getting the FDA's buy-in throughout every single stage is going to make those subsequent stages less risky. We can all hypothesize about what the FDA might like for a novel and complex device, but unless you've gotten their written sign-off, informal sign-off through the FDA pre-submission meeting minutes process,

You don't really know for sure. So every stage, every pre-sub that we do, we know we're de-risking that eventual marketing application. And that's a really important trail to have in place to show that this company knows what they're doing. They know what the process is and they likely have a large chance of being successful. So I'd say that, the two most important things would be thinking about who's on the team and making sure to engage early and often with the FDA.

to de-risk that process as much as possible.

Jesus Moreno (36:30.857)
Excellent. And are there any quiet red flags that you've seen be present in companies that go through the regulatory process successfully but end up not being ready for that scaling part of the process?

Kristen Mittal (36:49.25)
Yeah, yeah, I mean, I know there can be the allure to try to hide things from the FDA and think that they won't find out for major issues. But the FDA will eventually find out maybe not through the pre-submission process, but they will eventually when you go to go to do a marketing application, they will find out. So if that's kind of the nature or the approach to it for the novel complex devices, it's not a very good strategy and we see it not work a lot of the time.

Jesus Moreno (37:21.559)
Thank you. Thank you for that, Kristen. Thank you so much for sharing your insights with us. throughout this conversation, I can see that you've proven that regulatory strategy is not only about checking the boxes, but it's a competitive weapon that when thought through properly can be the difference between a startup surviving and failing and

Well, thank you for your commitment to educating the next generation and for sharing your background, your knowledge with us today. To our listeners, thank you for joining us and until next time, keep accelerating.

Kristen Mittal (38:07.472)
Great, thanks Jesus, thanks so much.