Med Device Darwinism: Evolving Epinephrine Delivery

By Doug Roe, Chief Editor

Last week, we spoke with Windgap Medical CEO Chris Stepanian about the challenges of entering the epinephrine delivery market, dominated by Mylan's EpiPen. This week, we go more in depth with the startup's CEO; he delves into Windgap Medical's device and development process in greater detail, and offers a peek behind the curtain at his company's down-the-road plans. 

Med Device Online: How does Windgap Medical’s technology work, and what differentiates it from other auto-injector devices on the market?

Chris Stepanian: The technology is actually pretty simple. It is, at its core, a compact, wet-dry auto-injector. It is particularly powerful because of its small size, and the fact that the mixing happens in an automatic and consistent way.

Our goal is to have a product where, with one simple action, we can enable a patient to move a drug from a dry, stable state into a solution that is ready for injection. Then, another simple action — basically, pressing the trigger against the thigh — would enable the drug’s delivery as an intramuscular injection, in the case of epinephrine. The current standard of care is either .15 milligrams (mg) or .3 mg of epinephrine in solution, delivered to the thigh as an intramuscular shot. We are not trying to change that at all. Our goal is to provide the same liquid dose as what is out there today.

What we aim to do is to store the drug a little differently until time of use. This is pretty similar to what we understand is done in the factory today, where pharmaceutical companies buy the dry drug form, drive it into solution on a batch basis, and then proceed to a liquid fill into an auto-injector device. We are just doing it slightly differently — we are doing it on-demand.

MDO: What were some of the drivers that led you to that device design?

Stepanian: Initially, we reached out to patients and allergists, and asked them what they liked and did not like about epinephrine injectors that they had interacted with. They definitely want something that is easy to carry. Patients were very concerned about the obtrusiveness of current designs. They wanted something that could fit easily in a pocket.

They also wanted something where the drug would always remain stable. Right now, putting your epinephrine auto-injector in your pocket — I’m guessing your pocket temperature probably is between 85 degrees and 95 degrees, especially on a hot summer day ­— is either borderline unacceptable or completely unacceptable storage temperature for the drug.

Parents, especially, were concerned that taking the device to the beach, having it at the soccer field, or accidently leaving it in the car would degrade the drug. They wanted something they did not have to worry about so much. We have enough things to worry about; you don’t want to worry whether medication is going to be potent when you actually need it.

Finally, users wanted a device that is intuitive to use — more intuitive than what is currently available. Some folks really enjoy additional features, like a talking device; others, not so much. We wanted to develop something that was simple and mechanical, that enabled safe and effective use, regardless of whether you understand English.

MDO: According to the FDA database for product failure, mistaken injection is one of the top failure modes reported. How did you address this issue?

Stepanian: When we surveyed our potential customers and users, they agreed mistaken injection was one of the top three areas for potential design improvement. We saw an opportunity to make a device that you just look at — no heavy thinking required — and you automatically know which end to push against the thigh.

A lot of folks get confused in the heat of the moment. If your child’s dealing with anaphylactic shock, you are going to lose a few IQ points. It may have been a while since the user last was trained, and sometimes the training is not the best. If you add all of that up — looking at the EpiPen, for example — you can get confused as to which end the needle comes out when you pull its blue tab.

If you read the EpiPen instructions, they are actually quite clear. But sometimes, people do not read them in the heat of the moment. Sometimes, they just try to remember, make a mistake, and take it in their thumb. That is a lose-lose situation, because you lose the dose that could have been delivered to the patient, and now you have to endure — since epinephrine is a pretty strong vasoconstrictor —a fair amount of pain in your thumb.

MDO: It does not appear you are following the trend of incorporating electronic capabilities into this device. Why not?

Stepanian: We thought about electronics early on, because Auvi-Q was just coming out, and the talking mechanism was one of the things investors and users were very interested in. We see audible instruction as a way to partially address some of the perceived issues with ease-of-use.

But, in our minds, that feature actually added some complications. You add electronic components and power supply to worry about and, if you choose to use the voice feature, you have various language issues to be concerned with.

We saw a path forward where we could make a mechanically simple, non-electronic based, intuitive device. Apple has done a great job creating devices that are very intuitive. That became our design MO. If we could aspire to create something as clean, simple, and intuitive as a typical Apple product, we would probably be well-served. It would be different way to address the ease-of-use issue, but to do so with just human factors engineering. That is what we started with and continue to work on — to understand what our design cues should be, and to refine the device so it is very intuitive, but still just a simple mechanical device.

Another argument in favor of keeping it simple, for epinephrine, is the fact that most auto injectors will be thrown away, unused, at their expiration date. Why make an electronically sophisticated, and consequently more expensive, disposable? The device usually goes untouched for the entire time you have it, and hopefully it will stay that way, until you throw it in the trash.

MDO: How have you moved those design concepts into the actual product development phase?

Stepanian: Brent and I are not medical device 30-year veterans. That is not our background. Our approach towards the market has been to open ourselves to learning. We have tried to set up as many situations as possible to learn, adjust, and redirect.

You know the old adage: “Fail early, fail often, fail cheap.” That is what we have tried to drive in through our design process. We do not like failing; you do not try to fail. But if you are going to have a failure, make sure it happens as soon as possible in that design process, so that you can adjust inexpensively, learn, and move on. That way, you can ultimately come out with a safe and effective product.

We have spent a lot of time developing very simple, very quick feedback loops to provide us with that input. For example, the team was adamant that they wanted a stereolithography (SLA) machine, and that has turned into a real bonus for us. Our director of product development has come up with an idea, designed it, printed it, and tested it — all within the same day.

In addition, we are in Massachusetts, and there is a number of very good injection molding shops. They may not all be suitable for final medical device production, but they are suitable for prototype modeling, learning, and quick turnarounds — figuring out what works as an injection molded part.

These approaches have really helped us to quickly figure out which design theories work and which ones don’t.

MDO: Where does your device currently stand in the product development lifecycle?

Stepanian: We have working prototypes now. We are effectively on our third generation. With the last round of money we raised, we are beginning to develop a pilot production line with a new manufacturing partner. We are also currently talking to marketing-sales partners — “go-to-market partners.”

Our timeline has us submitting to the FDA in a late 2017 / early 2018 timeframe. It would be through the 505(b)(2) route, a classic combination device submission. That’s the same path that Auvi-Q and Intelliject went through to get their products to market.

MDO: What is next for Windgap and your delivery device technology — short- and long-term?

Stepanian: We are in talks with other pharma firms looking to enable additional drug delivery opportunities that might benefit from our wet-dry auto-injector device. As you would guess, epinephrine is not the only drug we could potentially reconstitute automatically and allow for quick delivery to a patient. There are a number of APIs out there that do not do well in solution, either intrinsically or because they are very sensitive to the environment (temperature, light, etc.).

We are in the process of identifying what all those APIs are, and what kind of value we could bring by having them used in our product. There are a large number of them. Then, we are reaching out and talking to either the manufacturers of those products — or finding manufacturers of the API, if it is perhaps off-patent — and trying to see if we can find a good commercialization partner to help bring the product to market.

We are going to talk to a number of potential partners, not just for epinephrine, but for products two, three, and four — what we see might be good applications. These are early discussions, but we believe there are some opportunities out there that our likely commercialization partners would find pretty interesting.

MDO: What has been the initial response from those discussions?

Stepanian: Very promising. There is definite interest in epinephrine, and there is definite interest in some additional products. Let’s consider the future, it is a biologic, or a bio-better, or a bio-similar — reconstitution delivery of powdered and lyophilized drugs is not going away anytime soon. We want to be an enabling technology, to make it easier for patients to take medication. We want to create a technology that enables them to safely and effectively deliver that drug at home.