Target customers are patients with a brain aneurysm amenable to surgical clipping. This excludes patients who have aneurysms very deep in the posterior blood circulation of the brain, or the base of the skull, which are difficult to reach with a surgical approach, or those where the ratio of the neck diameter to that of the largest dome of the aneurysm is greater than 0.5.  The latter require surgical coiling. 

Approximately 35,000 people in the United States suffer from ruptured brain aneurysms, half of which are fatal, and half of which are amenable to clip ligation. With an approximate 10 million patient prevalence of brain aneurysms, and approximately 5% diagnosed, there are about 500,000 Americans who are eligible for treatment with our device. There are millions of potential patients globally (the world market for clips has been estimated at $40M).

Virtually all treated patients will require a post-operative MRI or CT scan to evaluate the aneurysm or another medical complication. Currently, surgeons are severely limited in their ability to provide adequate care for this very dangerous problem. The postoperative course is extended and many people die or become more ill because of the inability to either diagnose or monitor the progress of a treated aneurysm.

There has been a continuous effort to minimize MRI artifact throughout the evolution of clip technology.  Initially, clips were made with steels that had some magnetic properties; these were dangerous because they could move due to the magnetic field created by the MRI machine. Next, clips were made with non-magnetic steels that would not physically interact with MRI, but would nonetheless obscure images in CT and MRI.  The latest designs use titanium, which has less imaging artifact than steel, but still obscures images, especially given that the surgeon is trying to examine small features in the vasculature. 

There was a startup in the last decade that was attempting to make a ceramic clip concept which would be invisible under MRI/CT.  However, they had to incorporate a spring element made of titanium in order to hold the ceramic jaws together because ceramic is not a viable material for springs since it does not carry tensile forces. The product never made it to market.

We have a design for an MRI clip that is invisible under imaging (MRI and CT) because it is made of plastic.  All aneurysm clips on the market are made of metal because the designs employ a preloaded torsional spring that provides the clamping force. In order to generate the required clamping force with a spring-based design, a material with the stiffness of a metal (titanium or steel) is required because the size of the device must be very small. While effective at stopping the aneurysm, the metal clips distort MRI and CT imaging, thus precluding visualization of future complications.

Our design departs from this conventional torsional spring configuration and employs a snap-together hinge configuration, wherein the clamp has features that flex when squeezed by the surgeon's tool, and clip together at the required force.  Since this new device contains no metal, it will not affect MRI or CT imaging, yet it will stop aneurysms, in the same manner as current clip technologies on the market.

The material that we have chosen for the design is PEEK (Polyether ether ketone).  PEEK is commonly used in long-term medical implants because of its mechanical strength and biocompatibility.  Applications of PEEK include implants in orthopedics, spine, cardiovascular, and neurology - including deep brain stimulation. These precedents will help to reduce development and regulatory risk.

Another advantage of the plastic design is that it will be low cost.  Metal designs are handmade in a precision fashion requiring hand craftsmanship and are typically made in Germany and Japan.  Injection molding is inherently low-cost and scalable so that our cost of goods will be a fraction of that of the competition.

The PEEK clip will also improve time to treatment. Currently, surgeons address the lack of visualization by looking for alternative means of diagnosing post-operative complications, often times adding significant cost and vital time to finally obtaining a proper diagnosis. An artifact-free clip would eliminate this problem altogether.

In summary, as compared to the state of the art, the PEEK clip will be cheaper, allow clear imaging, and improve diagnosis and treatment time for people who have had an aneurysm that requires clipping.

Aneurysm clip companies use the Premarket Notification (510k clearance) pathway because the devices are class II medical devices and they have been on the market for over fifty years and the mechanical performance is standardized. To achieve 510k clearance we will be required to show that the new device is substantially equivalent to a predicate device (or devices) on the market.  The FDA has mandatory test standards that must be met for clips and these tests form the basis for our bench test plan and allow us to plan our bench testing accurately and reduce uncertainty.

Since our device uses a new material, we will be required  to do additional testing in order to validate safety.  This could require as little as doing some additional bench testing to possibly being required to undergo pilot human clinical studies.  We are likely to fall in between the two scenarios and require additional mechanical testing and perhaps animal studies for safety validation.  The choice of PEEK provides regulatory advantages over other non-metals due to its acceptance in implants throughout the body and its proven biocompatibility.

We have engaged IP council (Daniels Patent Law) and filed a provisional patent covering our current design embodiments. This gives us one year to file a utility patent in the U.S. and international via a PCT application.  As we progress in R&D throughout the coming year, we will file additional provisional patents as necessary.  We are also doing a patent search on our own to keep costs down, but the intent is to contract for a professional freedom to operate search before we file the utility application.

Our development plan for the next year involves technology development aimed at reducing development risk and much of this can be done with the funding from the competition. A rough outline of the plan is as follows:

Q1 2012-Q2 2012:  Detailed design and prototyping of leading permutations of our design. This includes computer simulations using finite element analysis (FEA) to predict stress and mechanical behavior, rapid prototyping using stereolithography (SLA) or selective laser sintering (SLS), and bench testing with force measurement.

Q2-Q3 2012: Take leading candidate designs into pilot molding in PEEK material.  Injection molding is the only way in which we can get prototypes made in the correct material because rapid prototyping is not possible with PEEK.  These injection molds will be low-run aluminum molds for quick turnaround and low cost.

Q3-Q4 2012:  Design for manufacturability.  Work with micro-molding vendors to create the net-shape design that we require.  Start manufacturing iterations with real molded parts. Continue with IP protection looking to our preferred embodiment and possible process related IP.

Q4+ 2012: Run bench tests as per accepted aneurysm clip methods to verify that the device meets the requirements for equivalency.  If the device meets the requirements then the R&D risk is substantially reduced and we will be ready to seek funding to go to the next level - regulatory approval.

There are only a few players in the aneurysm clip market (e.g. Aesculap USA and Mizuho) competing for a relatively small market, and these companies have an appetite for new technologies that will provide them with a competitive advantage.  Our strategy is to get the product through regulatory approval and pilot studies in humans, after which we hope to sell the company to one of the companies in the market or to a company desiring to enter into the aneurysm market.  However, a rough, top-down, estimate of the costs to market follows:

Proof of concept: We can reduce a lot of the risk out of the business with a relatively small investment ($60,000) which would get us to a working molded prototype.  This milestone would add immense value to the company because we will have a working design ready for FDA clearance and at that point we would have an assessment of what testing the FDA will require (i.e. animal models, etc.).  We will also have a potential licensing opportunity if large companies wish take our device at this point and continue with manufacturability and scaling. However, this is unlikely because most companies prefer to engage after regulatory approval. 

Regulatory approval: In order to get to a regulatory application we will need to execute the testing as per FDA requirements.   This will require pilot manufactured devices and a delivery tool made in the likeness of the product we will bring to market.  We will also need quality and manufacturing capabilities (potentially contracted).  This stage will require approximately $500k of funding.

Limited market release: With a product this simple, it will be feasible to start out slowly in order to reach the market and test out the ease-of-use and acceptance in specific surgical centers.  Thus, we could sell on the order of dozens of devices in the first year (after regulatory approval) using pilot manufacturing molds.  This will allow us to monitor the usage of the product and control the growth and distribution in the early stages. This is a low cost means to get into the market without creating an excessively large company and getting ahead of ourselves, as often happens with companies selling more complicated medical devices.   As such, the milestones include manufacturing devices with hard-tool molds and in a scalable manner, along with the quality, inspection, and manufacturing personnel required.  Furthermore, a limited distribution will be accomplished through thought leaders connected with the our surgeons. This stage will require approximately $1M of funding.

Market Ramp-up: If our product has preliminary acceptance in the market by thought leaders, the next step will be to expand the sales throughout the US.  We will likely do this by partnering with an distributer that has existing channels in the neurosurgery market. Marketing will include advertising and academic publication as well as conference proceedings and poster sessions. We will need to be capable of operating at full manufacturing capacity in order to accommodate a full-scale market launch.  These efforts could require up to $3M in order to get to a profit, at which point we can turn our intention to the European market.

Vijay Agarwal, MD, the principal investigator, is currently a second year Neurosurgery Resident at Duke University Medical Center. He did five years of medical device innovation before starting his residency, including helping to start a minimally invasive medical company that is currently in successful clinical trials with multiple rounds of funding. He has published and presented extensively, including book chapters, manuscripts, lectures, and podium presentations. He completed undergraduate studies in electrical and biomedical engineering at UCLA, and his MD from Chicago Medical School.

Craig Litherland is a biomedical engineer who has been doing early-stage medical device startups in Silicon Valley for most of his career, focusing on developing startups from inception through testing and clinical trials.  He has invented and developed the technology behind electronic aerosol generation at Aerogen (acquired by Nektar Therapeutics), invented the core technology of a novel blood glucose monitor (Intuity Medical), and created an integrated titanium spring that is used in spinal implants (Simpirica Spine).  Previously he was an automotive engineer doing automotive crash simulations on supercomputers.  His technical background is in mechanical and aerospace engineering with an emphasis on structural analysis (FEA) and design.  He holds a B.S. in aerospace engineering from the University of Michigan and an M.S. in mechanical engineering from Stanford University.

Robert Isaacs, MD, is a professor of Neurosurgery at Duke University Medical Center. He has published extensively, and has been acknowledged world-wide for his work in Neurosurgical Research. He completed his MD at Baylor College of Medicine, his Neurosurgery residency at Vanderbilt University Medical Center, and his fellowship in Endoscopic and Complex Spine at Rush University. He has a particular interest in medical devices, more specifically in minimally invasive spine, and has successfully invented, developed and sold multiple medical devices.

Use of Funds - if you won $50,000 how would you use it?

As alluded to above, we can gain a lot of momentum with the first $60,000 (using $50k from this competition and $10k self invested). These funds will help us get a true working prototype and an FDA application.  The funds will be used for the following expenses: $10k in structural analysis software, $20k in test equipment and/or equipment rental, $5k in rapid prototype iterations, $15k for prototype mold iterations, and $10k for regulatory advice.

Advisor:

Ali Zomorodi, MD, is a professor of Neurosurgery at Duke University Medical Center. He is a Duke veteran, having done his medical school training, his residency in Neurosurgery, and his Neurovascular Fellowship all at Duke. He has become a world expert in cerebrovascular and skull-base surgery, endovascular neurosurgery, acute treatment of cerebrovascular occlusive disease. He is an expert in intracerebral aneurysms and their treatment, with a particular interest in aneurysm clips.