In this Q&A, an expert gives medtech innovators advice on building a regulatory and commercial strategy early in the development cycle, including how to avoid an expensive and all-too-common mistake.

Marie Thibault

As vice president of the Global Medical Technology Division at Cambridge Consultants, Harshal Shah works with medical device companies and innovators during the product development process, helping them ready an offering for the commercial market. MD+DI asked him for his insights on the regulatory challenges that device inventors face. In addition to his thoughts on the FDA approval process and commercialization strategy, Shah pointed out a major misstep that is sometimes misinterpreted as a regulatory hurdle.

MD+DI: What do you think is most important for product developers to think about regarding regulation before they start building the product?

Harshal Shah: I think that the key is to identify what you are trying to address and, based on the current FDA guidelines, what category your product is going to fall into. The key is also to engage with FDA early on in your development cycle. FDA has improved drastically in terms of providing opportunity to interact with innovators early on, even before they start heavily investing into their development process. So, you can capture FDA's views on what you're thinking of doing and also, they are happy to provide a regulatory approval pathway so you do not end up assuming something which would be contrary to what FDA is going to think through. Obviously, none of the advice from FDA is binding. They can always take a different opinion once you formally submit the approval, but it still provides very valuable input into your regulatory and development strategy.

MD+DI: How does a medtech entrepreneur actually go about approaching FDA? Do they talk to someone locally, do they reach out to a director at CDRH? How does that actually happen, in your experience?

HS: They have a well-published process for requesting FDA's feedback and meeting with some of the key people who are directly involved and relevant to your innovation. Even before you go to request a designation, you can discuss with FDA the concept and there is an online mechanism where you can request FDA feedback on a medical device submission. So it's a very transparent and open process. Anyone who is actively working in developing or innovating in the medical device industry will know this process where FDA provides opportunity to connect with them, to request online a time to meet with FDA to capture their opinion on innovation and also provide guidance on a regulatory pathway. FDA is an overloaded agency, so they have limitations on how much time they will give you . . . I cannot speak on behalf of FDA, but in my view it may be a couple of months before you can get anything with FDA. But there are professional advisors available on FDA regulations. When these startups and innovators are trying to formally start their process, I would suggest they invest and plan out certain costs for hiring professional regulatory advisors or consultants to help them through, because it's a complex process . . . so that they are prepared to tackle the regulatory approval process.

MD+DI: There are plenty of initiatives at CDRH to encourage innovation: Parallel Review, early feasibility studies, the Expedited Access Pathway program. Do you have any experience with these programs and if so, what are your thoughts?

HS: Again, it depends on your product and the classification and the current need, as well. All those special assessments are available on a case-by-case basis. Not all innovators can rely upon getting those kinds of arrangements for the regulatory process. Even if you follow the traditional path of approval, there is room for making sure you avoid challenges at a later stage . . .

Also, consider your commercial and manufacturing feasibility early on. More often than not, all these innovators design something, they run trials with a certain design or version of the product, and later on they realize that they will have to make drastic changes to their designs in order to make sure that it can be produced cost effectively and that it can be manufactured for high volume.

That is where the biggest issue comes up--how do you establish the equivalence of design that you have run your trials with, that you have submitted the approval process with, and the commercial version that you would like to launch with? That essentially delays the process, introduces a lot of complexities in the process, and ultimately you end up thinking that it is regulatory hurdles that are impacting your innovation cycle, but that's not necessarily always true. I think that's another major pitfall that startups and innovating companies make--in fact, sometimes midsize and large companies also end up in this bucket. They fail to factor in manufacturing feasibility into the early designs that they run the trials with and then it becomes kind of difficult to establish equivalence with FDA and that runs into another development cycle, modification cycle, and the review cycle for FDA. So you end up putting in a lot of years on the development cycle because of that.

MD+DI: What's your advice to companies? Do they need to start thinking about the issue earlier? How do you help companies get through that?

HS: To give you some of the buzzwords you will hear come up in the manufacturing industry, there is Quality by Design and Design for Manufacturing. For example, Cambridge Consultants is a product development company. We have these dedicated experts who will analyze the concept design, even at the prototype stage, whether this is going to be practical to manufacture and what the cost will be, so that innovators or the clients can go back and think through whether this cost is really going to fit into the reimbursement scenario or not. If they decide at a later stage--this is the concept, it works, now let's go for approval--and at the end of the approval they think that this is very difficult to manufacture or the cost is so high that it's prohibitive in getting that product to commercial launch, then they go back to the drawing board and then they redesign the product. Which is something that we would like avoid at any cost.

This is where the Quality by Design and the Design for Manufacturing principles come into the picture . . . The product might be excellent, but it's not designed for mass production, it's not designed to maintain the quality of the product at mass production scale . . . Again, you have specific experts who specialize in Quality by Design principles and QbD audits and Design for Manufacturing audits of your design work. So, you can make those changes early on and produce your prototypes as well as the clinical trial devices in line with what you will be able to produce for commercial scale in the future, after approval.

MD+DI: What are some of the regulatory challenges that are particular to the mobile health and smartphone-driven technologies? What are the challenges you see most often there?

HS: I do not have direct experience with that area, however our firm is keenly interested and involved in that area as well. The key challenge right now is, it's a fairly new area for FDA to tackle. All the innovations that came as a result of a revolution in cell phone and smartphone device engineering, you have so many capabilities in smartphones nowadays that you can leverage for health monitoring, vitals monitoring, to cardiograms and urine tests and whatnot. I believe FDA is still forming their opinion on how they plan to regulate these apps and what they consider a device and what they consider not a device. Any apps that advise or help to determine certain conditions or provide support to the patient or caregiver, technically speaking FDA would like to regulate that, and it will come under regulation at some point in time. However, it's still kind of an evolving area . . .

You need to understand that the simple assumption is, if you're trying to bring diagnostics or a certain type of function onto your cell phone, it will probably get very similar scrutiny as a device that is in the hospital setting currently or the lab environment currently . . . If you're not prepared to go through that kind of stringent regulatory approval process that you would go through otherwise, then you are probably making the wrong assumption that it's just an app attached to a cellphone or a sensor attached to a cellphone. That's not how FDA is going to look at it . . . Rather than assuming things in your favor, you want to assume the most difficult pathway to regulatory approval and then you have a better chance of being prepared to manage what is coming your way.

MD+DI: Not too long ago, FDA put out guidance on mobile medical apps. I'm curious if you think there are other topics in medtech regulation where FDA has been particularly helpful in providing guidance? Alternately, are there other areas where you would like more clarity from FDA?

HS: I think FDA has, in recent times, done a really great job of improving their performance benchmarks. If you look at the IDE process . . . they have reduced the process down to less than 30 days . . . It's a drastic improvement from what it used to be. Looking at the kinds of challenging devices that come to FDA for IDE approval, it's no longer traditional . . . devices that they're dealing with. They have all these robotics and smart interoperable devices, the latest cutting-edge imaging devices, and genomic sequencing devices. Devices are getting more complex at the same time as FDA is improving their performance benchmarks, which, in my opinion, is really commendable. Not to say that there are no areas of improvement for the FDA process, but then, there are regulations for a reason. Their primary objective is to maintain the safety of public health. I would feel comfortable with FDA taking a more conservative approach than not. I think especially for Class II and III devices, they have been pretty proactive in providing guidelines.

As you mentioned, mobile health and medical data-related innovations are something that they're struggling to come to terms with . . . it will find a solution in due course. I have reviewed some of the commitments that FDA has published . . . and they do mention pretty openly their priorities in making the PMA and 510(k) applications smooth and shortening the timeframe. If you are really doing something super innovative and you're first in the industry, then obviously it's going to be a very complex process for FDA to work with you and understand what you're trying to innovate. Logically, you will spend more time than the people who are coming right after you in the similar innovation area.

Some of the noise that you hear in the industry also comes from a lot of inexperienced startups who do not understand the value of getting with FDA and understanding the regulations, the current regulations, the fast-updating regulations. They need to put some emphasis [on this] and they also need to budget for hiring either appropriate people or appropriate advice to understand the regulatory process early on. If they don't do that and then if they fail to get approval in the appropriate timeframe, they're going to be disappointed. That's not really the correct data point to observe . . . It goes both ways . . .

MD+DI: What did I miss? Is there anything else you'd like to discuss?

HS: My deep expertise is more towards the late end of the development cycle when you're preparing for your trials and approvals. Even before you think about producing your trial size batches for your new product, it's really a must to get a good understanding of how you're planning to get this product into the commercial market . . . Avoid a very costly regulatory pitfall because once you apply with a certain version or design and specs of your device, changing those specs will obviously add another round of regulatory review cycle. Not as long as the original cycle, but it's still considerable time to be lost in launching your product.

I can't emphasize enough this aspect of the product development cycle which most innovators tend to ignore because they're probably focused on whether this product works or not . . . It's wrong to assume that the regulatory process has delayed your project when the fact is that it's a lack of integrating your commercial inputs and manufacturing inputs at an earlier stage before you go for the approval.

This Q&A has been edited for brevity and clarity.

Marie Thibault is the associate editor at MD+DI. Reach her at [email protected] and on Twitter @medtechmarie. 

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