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Polymer Material Opens Door for Novel Stomach-Based Drug Delivery

Researchers developed a pH-responsive polymer gel that could enable the development of new swallowable devices and capsules with ultra-long drug delivery capabilities.

Kristopher Sturgis

Photo of Shiyi Zhang, postdoc at Koch Institute and co-lead author, holding a ring-shaped prototype, which can be folded into a swallowable capsule (shown on the right) for safe oral delivery .
Shiyi Zhang, postdoc at Koch Institute, holding a ring-shaped prototype, which can be folded into a swallowable capsule (shown on the right) for safe oral delivery.

A new pH-responsive polymer gel could enable long-acting devices to reside in the stomach for days, weeks, or even months on end following administration. This is a considerable feat given the body's determination to digest and pass along whatever enters the stomach.

The polymer, developed by researchers from MIT's Koch Institute for Integrative Cancer Research from MIT, can withstand prolonged periods of time in the stomach while releasing drugs over a period of time. The polymer gel is stable in the acidic environment of the stomach but dissolves in the near neutral pH environment of the small intestine, allowing it to pass safely through the gastrointestinal tract.

"There's a tremendous need for devices with the capacity to safely reside in the stomach," said Giovanni Traverso, Koch Institute research affiliate and one of the senior authors of a recently published study describing the work. "The ability to safely reside in the stomach enables the development of ultra-long dosage systems, which helps tackle the medication nonadherence problem. Many diseases suffer from non-adherence, from the treatment of malaria, to schizophrenia, and even cancer," Traverso adds.

According to the CDC, nearly 50% of medications prescribed by doctors are not taken as prescribed, and nonadherence is responsible from between 30-50% of treatment failures, resulting in roughly 125,000 deaths each year.

This goes to show why Traverso and his colleagues believe that single-administration delivery systems can have such a big effect on so many different treatments.

Drug-delivery systems like this one are the subject of considerable research. Traverso's research, however, is unique in that it is investigating a delivery mechanism in the stomach over the long term. Traditionally, the stomach has been traditionally viewed as a short-term delivery pathway. In addition, much of the research on recent drug delivery research has been related pathways other than the stomach--direct injection into the brain and targeted nanoparticle delivery to cite two examples.

According to Traverso and his colleagues, the stomach is an area rife with opportunity for prolonged drug delivery systems, which is why this polymer gel could become such a crucial development.

The novelty of the gel lies in its ability to dissolve into the intestines, something existing polymers have been unable to do, making it difficult for them to pass through the body. To solve this problem, these researchers synthesized an elastic polymer and combined it in solution with a clinically used enteric polymer. The result was a polymer gel that contains both elastic and enteric properties, the elasticity allows it to be molded into a dosage form, while the enteric properties allow it to remain stable in the acidic environment of the stomach before dissolving in the small intestines.

"We see this technology inspiring the development of various devices," Traverso said. "Including those for drug delivery, as well as monitoring of various physiological and pathological parameters."

For now this team hopes that the material could be a big step toward single-administration drug delivery systems, and could eventually be used to create extended-release systems through swallowable pills.

Refresh your medical device industry knowledge at MEDevice San Diego, September 1-2, 2015.

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How Philips Made App-based Ultrasound a Reality

Previous innovations, and collaboration with FDA, helped Philips when it came to creating ultrasound that simply plugs into a smart device, says a Philips vice president who helped lead the project.

Randy Hamlin Philips
Randy Hamlin

Chris Newmarker

Royal Philips in September will start selling an FDA-cleared ultrasound transducer called Lumify that simply plugs into a tablet computer via its USB port. The interface runs off an app on the tablet.

Call it the birth of app-based ultrasound.

Qmed recently interviewed Randy Hamlin, vice president and business segment leader of Philips Ultra Mobile, to find out more about Lumify, and the design and regulatory challenges overcome to make it a reality:

Qmed: Which technological advances made app-based ultrasound possible?

Hamlin: While I was [vice president of R&D at Philips Healthcare], we were looking at feasibility projects that were interesting, but didn't know whether they were technically possible. About 12-plus years ago, we created this technology where you put more of the electronics in a transducer. We were doing that because we were creating the world's first real-time 3-D ultrasound imaging transducer. In order for us to do that, we had to take more of the electronics that were in an ultrasound cart, and place them in the transducer so that you could use up-front processing. There was so much information being generated by thousands of little elements that were transmitting sound and receiving sound that we would have to have a huge cable that would go to this large processor. We had to invent what we called a funnel technique, funneling all this information to a more reasonable mount. It requires us to have this processor in the transducer.

You go back about five years ago from today, there was a group of engineers in my office, and we were asking: "Why don't we take this approach into the 2-D world?" There were some feasibility projects we started to adapt to that same concept. That was the birth of app-based ultrasound. It's really centered around the ability to put all the electronics in the transducer itself, in the device that couples to the patient. That frees you up to then have a CPU and display device at the other end of the wire. For us to achieve that, we needed highly capable electronics in a low-power format, so we just use the power from the smart devices. That is fundamentally a breakthrough.

If you look at taking any off-the-shelf smart devices, it's really about being able to leverage miniaturization and low-powered electronics to then power your device from smart devices. That was really the breakthrough that allowed us to take app-based ultrasound to the next level. That's how the birth of it happen.

Philips Lumify
This marketing image from Philips shows the Lumify in action. (Image courtesy of Royal Philips)

Qmed: Why is app-based ultrasound so beneficial?

Hamlin: Your world opens up. You have all this amazing flexibility. That's where we see app-based ultrasound being so exciting for us. It fits on this very smart platform of smart devices. It allows us to constantly update content to our users in a very simple way. It's like accepting your app updates that you have on your smart device today. It eliminates the complexity and overhead of our customers have to wait a long time for software upgrades. There are some really amazing things that open up as a tool solution when you go to an app-based iteration.

Ultrasound that you can carry with you has been in the market a couple years now. What they struggle with is the image performance. The clinician really needs critical information at the bedside. We were able to overcome that through the Philips innovation migrating from real-time 3-D ultrasound to the 2-D world. We were able to deliver high image quality in an affordable solution. ... It sits on the user's own smart device. They're highly connective, ... solutions that are connected [to the electronic medical record] ... in a very seamless way. They can put their own security services on that device to protect their own device. The whole security thing is being taken care of as well. ... It's a bring-your-own-device solution. ... We fit into the existing paradigm of tools they already have today.

Qmed: Lumify is presently compatible with the Android Nexus 7-inch tablet, but the goal is to have it compatible with most Android and Apple devices in the future?

Hamlin: Our intent in the future is to be ubiquitous to the operating systems. ... Our first app is an imaging app that does a lot of ultrasound things. Over time, we'll be adding additional capabilities, a lot of other applications that are simply downloaded by our customers, other transducer types, other tablet devices with other operating systems. We'll be delivering that through a Web portal that is part of our solution.

It's the innovation of the transducer coupled with the user's smart device. And then that's coupled to our Web portal that enables them to access training materials, the latest app information. They can manage their devices through our cloud app dashboard that we have. And so if an institution has about 10 or 12 of these, they know where they're at in terms of who is using them and how much they are being used. ... In the future, many institutions will have to track utilization and how many criticals they're doing, because they'll have to do accreditation.

Qmed: Why are you offering Lumify under a subscription model?

Hamlin: Many customers are interested in doing more ultrasound, but ... they don't want to go through the process of acquiring a $30,000 ultrasound. ... With our subscription model, there's no upfront fee to start, and there's no penalty for exiting at any time. We're doing this because, No. 1, it really breaks down another barrier of adoption, which is large capital expenditure. It gives our users flexibility where if the demand of patient care increases, they can add subscriptions very quickly. If they demand drops, they can drop some subscriptions. ... It really matches access of ultrasound to the demand of healthcare.

Qmed: How much is the subscription going to cost?

Hamlin: I can't share pricing yet, because we're still finalizing pricing. But we'll have it available in September when we're rolling the product out. Our incentive is to make it very reasonable for our clinicians. We want to have them say, "Wow, I can use ultrasound. There's not a barrier for me." Our goal is to make it a really attractive subscription.

Qmed: Where do you think this will initially be used?

Hamlin: The first market we'll be going into will be the critical care market within hospitals. They want something readily available to them at bedside or on the floor of hospital or in the ICU. Also, the emergency department can have easier access to ultrasound for trauma patients as they come in. Outside of the hospitals, there are sports medicine clinics. ... And over time, we see them going into urgent care centers ... long-term care centers.

Qmed: Tell us more about the open apps platform and the Philips' Ultrasound Consortium?

Hamlin: Our intent is to work with the consortium members and non-consortium members to help us develop app ideas. ... We find it's valuable to share ideas. ... What we're offering this fall is what I call the beginning of a development platform. It's a very open platform. Our intent is to one day offer a development kit, and they can develop their own apps. That's why I'm excited about it. It's just the beginning. ... We really see the future users being contributors for future applications.

Qmed: What level of FDA regulation does the Lumify have?

Hamlin: It's a Class II ultrasound device. We already have a 510(k) for our first transducer. And we're working on other transducers that will need 510(k) clearance. ... This can only be used by physicians and qualified purchasers of medical devices, so this is not available to the consumer to purchase.

Qmed: How did you navigate regulatory hurdles related to potentially plugging into so many different smart device platforms?

Hamlin: We're breaking a lot of new ground with Lumify, so we've been collaborating a lot with the FDA. ... We have minimum specified requirements of the smart device displaying ultrasound. The FDA has agreed to that minimum specification. They're very comfortable saying that anything that exceeds that minimum specification is underneath the 510(k). We have established where the bar is based on resolution and power of the smart device. And on apps that are developed, Philips takes responsibility that any app offered on our platform has 510(k). A 510(k) is required. ... We're the gatekeepers of that. ...

We have found Android devices that do not function consistently with others. So our website will include a qualified list of smart devices that we guarantee are compatible. And then we will have our minimum specification that will say these other devices [that surpass it] may work, but we will not guarantee them.

Qmed: Anything else that would be good to add about Lumify?

Hamline: I'm excited about how this could change healthcare so much. We're trying to change healthcare and keep people out of hospitals.

Refresh your medical device industry knowledge at MEDevice San Diego, September 1-2, 2015.

Chris Newmarker is senior editor of Qmed and MPMN. Follow him on Twitter at @newmarker.

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A Conversation with a Corporate Venture Investor at J&J

A Conversation with a Corporate Venture Investor at J&J

A corporate investor at Johnson & Johnson shares the company's venture investment philosophy at a time of change in healthcare. 

Arundhati Parmar

Renee Ryan is the vice president of investments at JJDC, the venture arm of Johnson & Johnson. She will be a speaker on the funding panel at MEDevice San Diego, Sept. 2, an event hosted by UBM, which publishes MD+DI.

Recently, in a phone interview, she described JJDC's investing philosophy, what she looks for in device firms and her excitement when she comes across a promising device startup, with cool new technology and headed by a female CEO.

MD+DI: How has JJDC evolved since its founding? 

Ryan: JJDC has been as been around now since 1973, which is really when the venture capital industry itself was formed.

I would say over that whole time frame, we have always been a strategic investor though we’ve pivoted in and out from strategies that are close to J&J’s three businesses to those that are farther away.

I think today our investments across the pharmaceutical, consumer and medical devices businesses are more closely aligned to those businesses and have a strategic mindset.

We also tend to be stage agnostic meaning that we have no preference for earlier or late stage. We invest across the spectrum — everything from new company formation activity to seed financing to later stage financing. On the consumer end where we are talking about channel and market positioning, we tend to be later stage, and earlier on the devices and pharmaceutical ends.

The JJDC group itself is fairly small with only nine active investors. Two years ago, when our four regional innovation centers were formed, we moved investors to those regions. They are in Silicon Valley, Boston, London and the Asia/Pacific region which is based in Shanghai. And one is in Tel Aviv, Israel.

MD+DI: How would you say JJDC differs from a traditional VC firm?

Ryan: Very specifically, all of our investments lead with the corporate strategy and that really distinguishes us from any traditional venture capital firm, which does more of a financial analysis for their early stage investing.

Secondly, I would say that we don’t have a dedicated fund. We think more about the capital deployed and the timeline to hit the milestones versus a single fund having a seven to 10 year life.

Our incentives are very like those people who drive J&J's businesses — getting the next blockbuster compound into a development cycle for our pharmaceutical business and the next important surgical innovation for our orthopedic or surgical businesses.

So it is really around the strategic outcomes of the portfolio. In medical devices, it tends to be more acquisitions driven, so sometimes we will count a distribution relationship or some other relationship as a strategic outcome for the business. 

MD+DI: How often does it happen that JJDC makes an equity investment in a company and then the company gets acquired by J&J later?

Ryan: We generally will say that approximately every 18 months J&J will do an acquisition of something that is in our portfolio. Where it gets a little tricky is when you look at our biopharma investing. We may invest in a company that has three programs underway, and out of programs A, B and C , J&J will in-license C and that then goes into our pipeline.

That “counts” as strategic on boarding but the reality is that JJDC remains an investor, and we still hold the equity in that entity going forward. So it might go public, and it might get acquired by somebody else. So the biopharma portfolio has the potential for more outcomes than just a pure M&A outcome.

A venture-backed medical device company typically has one product and they are focused on bringing that product to market.

MD+DI: How are you looking at medical devices investing these days?

Ryan: It’s hard for us to build a very large portfolio of early stage assets. So what we have tried is to look at a three-to-five year time horizon. What we have done is actively supported activities such as Medtech Innovator, which provides prize money to a promising startup through a contest. The finals are at AdvaMed 2015 this year in San Diego in October. That helps an early stage medical device company win some prize money.

We’re also very active with Stanford Biodesign and any ancillary activities around company formation. You’ll see more and more us doing those kinds of activities.

That being said last year we made several new medical device investments, one of which was a Series A round in a relatively new startup company.

MD+DI: Could you tell us more about this startup?

Ryan: Sure. It's called Cala Health and the technology was originally developed out of Stanford Biodesign. The technology is a very interesting therapeutic wearable device for movement and other disorders.

And then the CEO was a woman, so I was excited about that. You have an early stage company with super cool wearable technology and a female CEO, and I was like 'I got the winner winner chicken dinner.'

MD+DI:  What drives your investments in devices? Can you mention any technologies that you see as game changing?

Ryan: I think at the core of what we hold ourselves to is investing in transformational innovation. If it's a turn off of our current platform, we should be doing it with our internal R&D resources. So we do look for something that is breakthrough technology and breakthrough innovation. 

We never used to have any health economics analysis, and right now we have them for every investment we do, whether devices or not. For an earlier stage company, we would want a path to reimbursement. For a later stage company we would want a tighter answer to reimbursement. 

But ultimately it's about the people. I will go back to the Cala Health startup example. I didn't know the CEO at Biodesign but got to know her later and then having someone like Scott Delp, who is a well-known serial entrepreneur, academic type here in Silicon Valley was really important for us to make that early stage investment.

As for game changing technologies, is there a way to take a highly invasive procedure and make it minimally invasive? Are there disease states where you can use a procedure and reduce the drug burden and improve patient outcomes? So those types of technologies and potential opportunities are front and center for any investor in the marketplace whether they be strategic or financial. 

MD+DI: How are you looking at global investment especially in Asian companies?

Ryan: This might be a bias that we have today but for large corporate players because there is so much capital in China in particular, we don't tend to see the more cutting edge early stage innovation in those markets. Those opportunities really go to the local, China-based investors.

We are seeing a lot of Asian money come to the U.S. market and help fund U.S. companies. 

Earlier this year, we announced that we have contributed $15 million to Vivo Capital's latest fund so as to tap into more directly a local investor in the Asia market for medical device and pharmaceutical innovation. It's a very rare activity for us. 

We were not prepared to put a medical device investor there just yet and we thought that Vivo has been a phenomenal partner to us for many many years across our businesses so we felt very comfortable investing along side them.

[Photo Credit: JJDC] 

Arundhati Parmar is senior editor at MD+DI. Reach her at arundhati.parmar@ubm.com and on Twitter @aparmarbb

To learn more about medical devices and trends in the marketplace, attend the two-day MEDevice San Diego conference, September 1-2 

FDA Signals Willingness to Relax Clinical Trial Requirements

FDA Signals Willingness to Relax Clinical Trial Requirements

An FDA official gives a concrete example of how the agency decided that clinical trials without a control arm could be used to assess a certain type of device.

Marie Thibault

Here's a message to those in the medical device industry who think the FDA regulatory process is too complicated: FDA is already streamlining requirements.

That was the word from Ben Fisher, PhD, director of the Division of Reproductive, Gastro-Renal, and Urological Devices in the Office of Device Evaluation at CDRH. Fisher wrote in a recent FDA Voice blog post that the agency recently determined that it would be possible to evaluate future global endometrial ablation (GEA) devices using clinical trials that don't have a control group. 

Fisher's example was a specific one, so it doesn't mean FDA will allow single-arm trials for all types of medical devices. He wrote that five different GEA devices have received FDA PMA approval since 1997. All of these devices were evaluated through clinical trials with hundreds of patients randomized to either the new GEA device or rollerball ablation. 

FDA decided to examine whether the data from these trials could be used to allow for a simplified trial design with future GEA devices. FDA conferred with industry and advisory panel members from the Obstetrics and Gynecology Devices panel and decided to use an "objective performance criterion" (OPC) statistical model to come up with the "minimum acceptable success rate for demonstrating device effectiveness," Fisher wrote. 

Fisher didn't delve into the details of the OPC in his post, but wrote that "FDA will post detailed information on how we developed this OPC on our website soon." 

"The FDA's development of an OPC means that less burdensome clinical trial designs without a control group may be appropriate for clinical studies of GEA devices, resulting in studies that require fewer subjects, thereby reducing the length and cost of such clinical trials compared with RCTs," Fisher wrote. Also, patients are more likely to sign up for such trials because they would be sure to be treated with the new device, as opposed to older technology, he pointed out. 

So while the GEA example isn't necessarily a widespread one, it could be meaningful for other types of devices. The concept of adjusting trial designs as a technology evolves isn't new either. In the past, FDA has ok'd trial designs for next-gen transcatheter aortic valves (TAVR) that compare against commercial TAVR instead of against surgical valves, as TAVR has become standard of care for patients. This is done partly to make sure new devices meet the existing commercial standard and partly because a trial randomizing some patients to surgery would be harder to enroll with commercial TAVRs available on the market.

"Strengthening the clinical trial enterprise" is one of FDA's strategic priorities and Fisher wrote that the priority "includes finding ways to streamline clinical trials so that fewer resources are required to bring a new device to the market."

And that makes it seem likely that more examples like the GEA devices may be on the way.

Learn about the latest medical device technologies at the MEDevice San Diego conference and exposition, September 1–2, 2015.

Marie Thibault is the associate editor at MD+DI. Reach her at marie.thibault@ubm.com and on Twitter @medtechmarie

[Image courtesy of STUART MILES/FREEDIGITALPHOTOS.NET]

 

Who Has the Most Interesting Desk in Medtech?

A person's desk can say a lot about what's important to them and how they get things done. What can each other's desks and workspaces teach us about the medical device industry? Let's find out.

Chris Newmarker

Chris Newmarker Desk
My desk in my home office, outside Minneapolis

They're the places where many of us get things done. They're the places where the magic happens.

Desks and workspaces also can say a lot about their owners and the industries they work in. (Email me at chris.newmarker@ubm.com with a picture of your desk or workspace, your name and title, and a description of what's there and what it indicates about working in medtech.)

Take my home office desk, for example. I'm a writer and editor, and I like some open space to take notes, in the same way that each day can arguably be a blank slate when it comes to what I am going to write and create.

Note the bobble heads that were actually awards (called "Sammies") that I won when I was at Minneapolis business newspaper Finance & Commerce, and the poster for the Minnesota Society of Professional Journalists, where I have been an officer in recent years. Or how about that cat scratching post? Better the Maine Coone scratch the post than the rug.

Frankly, my desk is a bit boring. Or maybe I just like to preserve some form of harmony?

Journalists' desks aren't always so organized--far from it. In fact, some of the best journalists' I've known had messy desks. When I was at the Associated Press' New Jersey bureau, there was a veteran reporter who had so many journals and notes piled up around her desk that they created a fort around her. Her library of clutter was a testament to the breadth of knowledge and insights she had gained on her beat over the years.

Perhaps it is time I stopped cleaning my office.

"If a cluttered desk is a sign of a cluttered mind, of what, then, is an empty desk a sign?" Albert Einstein reportedly said. The late, great Steve Jobs also reportedly was a messy desk person.

On the flip side, the majority of American workers say they judge coworkers over how messy their desks are, according to a survey by staffing firm Adecco that was recounted by Forbes. There is also the argument that removing clutter is a kind of reset that clears the way for new endeavors.

Earl Bakken DeskDesks can take all kinds of forms. There are standing desks and even treadmill desks to promote health. Maybe two workspaces might help.

And then check out this gem from Medtronic founder Earl Bakken's website: He's at work at Medtronic in 1950 in the flannel shirt and jeans "uniform" of those early years. By 1957, he had developed the first battery-operated external pacemaker. The rest, as they say, is history.

Does your desk show that you're an Einstein or a Bakken, or just your own cool, unique medtech designer or engineer? I want to collect some pictures and show off some of the most interesting-looking desks in the medtech industry. Email me at chris.newmarker@ubm.com with a picture of your desk or workspace, your name and title, and a description of what's there and what it indicates about working in medtech.

Refresh your medical device industry knowledge at MEDevice San Diego, September 1-2, 2015.

Chris Newmarker is senior editor of Qmed and MPMN. Follow him on Twitter at @newmarker.

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Stryker CEO Takes Happy Warrior Stance to Bundled Pricing

"We'll have the same pressures we had before," said Kevin Lobo, when asked about a proposal to bundle Medicare payments for hip and knee replacement procedures.

Kevin Lobo Stryker
Kevin Lobo, CEO of Stryker

Chris Newmarker

Stryker CEO Kevin Lobo appears unfazed over a CMS proposal meant to promote "quality over quantity" with hip and knee replacement procedures, which are big business for the company.

The proposed five-year payment model would have Medicare still paying healthcare providers in 75 geographic areas under existing payment systems. But hospitals where the surgical procedures take place would be accountable for quality and costs of care through 90 days after discharge. Depending on overall quality and cost performance over the 90 days, a hospital could end up receiving extra money from Medicare--or it could end up owing Medicare money.

"Once they start to focus on the total episode of care in a bundled payment, they tend to make much more focus on post-acute costs, which frankly outpace the cost of an implant," Lobo said in a recent earnings call with analysis, transcribed by Seeking Alpha.

"So we see this as a trend that really doesn't disrupt the implant pricing. We'll have the same pressures we had before. If anything, it might start to drive them to rationalize towards less suppliers of implants. In that world, we like that kind of consolidation to us is an environment where we feel we're well-positioned to win."

Lobo said Stryker has seen such bundled pricing in pockets, and it hasn't adversely affected Stryker's business.

"It's like I say, the post-acute costs are very significant and once they're shown in spotlight that's where I believe more of the focus will be placed than on the implant cost. That's not to say the implant costs are not immune from price pressure, but I don't see it as a new catalyst," Lobo said.

Kalamazoo, MI-based Stryker competes with Johnson & Johnson, Zimmer Biomet, and Medtronic in the space.

"By focusing on episodes of care, rather than a piecemeal system, hospitals and physicians have an incentive to work together to deliver more effective and efficient care," Health and Human Services Secretary Sylvia M. Burwell said in a news release. "This model will incentivize providing patients with the right care the first time and finding better ways to help them recover successfully. It will reward providers and doctors for helping patients get and stay healthy."

Concerned parties have until September 8 to submit comments on the proposal. More information is available on HHS's website.

Refresh your medical device industry knowledge at MEDevice San Diego, September 1-2, 2015.

Chris Newmarker is senior editor of Qmed and MPMN. Follow him on Twitter at @newmarker.

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Medtronic's CEO Made a Ton of Money Last Year

Much of Omar Ishrak's $39.5 million in compensation was related to Medtronic's $48 billion merger with Covidien.

Medtronic Omar Ishrak
Medtronic CEO Omar Ishrak

Chris Newmarker

Total compensation for Medtronic CEO Omar Ishrak skyrocketed to a whopping $39.5 million for the company's fiscal year ended April 24, according to Medtronic's recently filed proxy statement with the SEC.

The $39.5 million amount would make him one of the highest paid CEOs in the medical device industry. About $25.6 million of the compensation, though, was mostly to help Ishrak pay for the special U.S. excise taxes he and other top Medtronic executives personally owed after the January closing of Medtronic's $48 billion acquisition of Covidien. (Here's a timeline of the deal.)

Such excise taxes came on top of capital gains taxes that Ishrak and all other existing Medtronic shareholders owed after the deal had them swapping the old Medtronic stock for stock in the new Medtronic plc, said Medtronic spokesman Fernando Vivanco.

"They also have to pay their capital gains tax like every other shareholder does," Vivanco said of the senior leadership.

The acquisition allowed Medtronic to move its official headquarters from Minnesota to Ireland, saving money on U.S. taxes over the long-term. Many companies involved in such inversion deals have justified tax reimbursements to top executives because the excise taxes would otherwise penalize the executives for pursuing a strategy that financially benefitted the company.

Medtronic says in its proxy statement: "The payments are required to neutralize the effect of the excise tax so that [named executive officers] were neither harmed by, nor benefited from, the transaction."

That didn't stop long-time shareholders, including some among the companies' earliest employees, from giving Ishrak an earful during the company's annual meeting in August 2014. Ishrak responded that he understood the shareholders' pain over the capital gains taxes they needed to pay. A shareholder lawsuit was filed in federal court over the compensation plan, but a U.S. District Judge in Minnesota declined to issue an injunction in December, according to the Star Tribune of Minneapolis.

Ishrak's $39.5 million in total compensation handily exceeded what most other top medtech CEOs received in their company's most recent fiscal years. That included $25.0 million for Johnson & Johnson CEO Alex Gorsky, $9.1 million for Stryker CEO Kevin Lobo, $10.5 million for Boston Scientific CEO Michael Mahoney, and $10.2 million for St. Jude Medical CEO Daniel Starks.

Total compensation for Ishrak was $9 million for the 2013 fiscal year and $12 million for the 2014 fiscal year.

Ishrak's salary rose slightly to $1.5 million in 2015. The salary was more in line with Ishrak's peers such as Gorsky ($1.5 million), Lobo ($1.1 million), Mahoney ($921,302), and Starks ($1.1 million).

For fiscal year 2015, Ishrak also received nearly $3.5 million in stock awards, $3.1 million in option awards, $5.6 million in non-equity incentive plan compensation, and $192,470 in changes to the value of his pension.

Ishrak is often cited as a top CEO in the medical device industry. Qmed readers picked him as best medtech CEO in a survey last month.

Refresh your medical device industry knowledge at MEDevice San Diego, September 1-2, 2015.

Chris Newmarker is senior editor of Qmed and MPMN. Follow him on Twitter at @newmarker.

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Synthesizing Graphene Quantum Dots into Bioimaging Probes

Researchers are exploiting the nontoxic, fluorescent capabilities of quantum dots to enhance medical imaging.

Kristopher Sturgis

A group of researchers from San Jose State University (SJSU) believe graphene quantum dots could be the next big step in bioimaging technology.

While working on their masters in biomedical engineering, Aneshkumar Tilwani and Hildegarde Bell teamed up to explore the potentials of small crystals of graphene with a diameter of less than 50 nanometers--something known as graphene quantum dots (GQD). Bell initially found a few articles detailing the synthesis of silicon quantum dots, and theorized that through a similar synthesis process, the same could be done with graphene. Upon their first batch of synthesized GQDs, they noticed a distinct trait in the tiny crystals.

"Our first initial batch exhibited fluorescence under a UV lamp," Bell said. "The results of PL testing showed luminescence using excitation in a range of wavelengths."

More specifically the dots showcased a transition of photoluminescence from blue to green as a result of this excitation in the UV and visible wavelength ranges. They also found that GQDs are soluble in a variety of organic liquids including water, and unlike other semiconductor-derived quantum dots, GQDs have shown to be nontoxic in cultured cells and in animal studies. A fact that makes them suited for applications in bioimaging and biosensing technologies.

"This could potentially manifest into an injectable dye as a contrast agent to image blood vessels without the need for ionizing radiation to penetrate through tissue," Tilwani says. "It could be used in localized imaging devices, such as mammography, and could be another tool in medical imaging."

Given all of its potentials, keeping up with the latest in graphene advances is becoming almost a weekly endeavor. Just a few weeks ago, researchers from the University of Illinois at Urbana-Champaign discovered a new method to forming 3-D shapes from 2-D sheets of graphene, an approach that they hope will lead to new integrated systems of microelectromechanical systems with hybrid devices and flexible electronics.

While graphene's superior conductivity traits are well known, some of the photoluminescent properties that Tilwani and Bell discovered in the GQDs could lead to advances in bioimaging technologies, including the possibility of tumor imaging and cancer detection.

"We believe the technology can be enhanced by targeting the GQDs," Tilwani says. "For example, targeted imaging can have applications in cancer detection, and the GQDs could even be modified into a drug for photodynamic therapy which can be used to kill cancer cells.

The team--which also includes Jose Alvarez, a biomedical engineering student at SJSU, and Folarin Eorgbogbo, PhD and assistant professor at SJSU--believes the technology could also make its way into wearables, as it can be used to create biocompatible electric circuits that can enhance electronics and more.

"We see this project developing into some type of biosensor application that uses GQDs in the circuitry," Tilwani said. Although we think our technology could be used to potentially image tumor cells as well, there is a lot of work to be done our end to achieve these feats."

While many challenges still lie ahead, the group remains determined to explore every possible avenue that the technology unlocks, in an effort to maximize the efficiency and effectiveness of GQDs. They even hope to identify several wearable device technologies that GQDs could be easily adapted into, as they try to evolve the technology into as many forms as possible to enhance the world around us.

Refresh your medical device industry knowledge at MEDevice San Diego, September 1-2, 2015.

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Smart Inhaler Startup Announces New FDA Wins

A Madison, WI-based startup's digital health platform for managing respiratory ailments is gaining momentum in the United States.

Brian Buntz

Propeller Health
Propeller Health's platform automatically tracks the time and the location a dose of inhaler-based medicine is administered.

One of the biggest barriers to effective management of asthma is medication nonadherence, which can range from 30-70% according to various studies.

Founded in 2010, the startup Propeller Health (Madison, WI) has addressed the problem by devising a sensor and corresponding app to help patients track their symptoms and use of medications.

Last week, the company was able to expand its clinical claims in the United States to include improving medication adherence. "There is a significant clinical literature that shows audiovisual reminders on inhaled medications will increase adherence," says David Van Sickle, CEO and cofounder of Propeller Health. The company was able to boost its claims in part through internal clinical data.

FDA has gradually permitted the company to market its technology for an ever wider range of applications and asthma platforms since 2012. Most recently, the company obtained clearance for use of its technology with the GlaxoSmithKline Diskus dry powder inhaler and Boehringer Ingelheim's Respimat inhaler, marking the first time the system can be used to track daily medication use rather than only emergency-based medication use.

In March, the company announced FDA clearance of its technology for use with Boehringer Ingelheim's Respimat inhaler for COPD.

Propeller Health's technology can be used to drive adherence via messages on a user's smartphone in addition to email- and text-message-based reminders. The system is also compliant with the Qualcomm Life's 2net Hub.

A significant body of clinical data shows that the use of inhaled medicine can significantly improve the treatment of both COPD and asthma.

The company also leverages software to help identify patients' whose symptoms are worsening.

Van Sickle sees tremendous promise in the use of smart inhalers to improve drug adherence and reduce patients' symptoms. "What would you do today if you wanted to improve the treatment of respiratory diseases, and there were no more advances in the medications used to treat them? What would you work on?" Van Sickle asks. "You would work on increasing adherence. You would try to improve inhaler technique. You would use digital tools to track how effectively we are using the medications and to measure and ultimately improve patients' satisfaction with therapy," he adds.

Van Sickle says the company's technology can be used to help deliver personal insight to patients that help them have a deeper understanding of their symptoms, which in turn helps doctors better manage them. "That is a huge part of the promise of smart inhalers: for the first time, information about the day-to-day burden and management of respiratory disease can now be put to work."

The company's technology is in use in 35 commercial programs at facilities across the United States, including healthcare systems, employers, and payers.

Refresh your medical device industry knowledge at MEDevice San Diego, September 1-2, 2015.

Brian Buntz is the editor-in-chief of MPMN and Qmed. Follow him on Twitter at @brian_buntz.

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Embracing the Promise of 3-D Graphics for Medical Design

Embracing the Promise of 3-D Graphics for Medical Design

Arenas like oncology, orthopedics, obstetrics, and cardiology are relying on enhanced imaging technology in all phases of the healthcare spectrum, from clinical research to real-time patient diagnosis and treatment.

Medical imaging is a volatile arena—changing rapidly, filling gaps in medical knowledge and becoming an essential factor in improving patient diagnosis and treatment. Quickly advancing from high-resolution imaging to 3-D volumetric scans, sophisticated graphics are at the core of many new healthcare improvements. For medical designers and OEMs, the jump to 3-D may be unfamiliar territory and more complex than anticipated, in that it requires an understanding of commercial graphics components as part of an embedded design strategy. To capitalize on the long-term promise of 3-D imaging, a greater focus on materials planning is crucial during the earliest stages of strategic development, ensuring the ideal balance between peak performance and system availability, longevity, and consistency.

Commercial Graphics Cards Lead in 3-D Performance

A regular pace of x86 advancements has improved on-chip graphics, yet the graphics features on fourth-generation Intel Core processors are optimized only for 2-D media applications such as high-resolution imaging or playback of high-definition video. As medical applications are starting to demand more, newer commercial graphics cards provide an alternative that does not bottleneck CPU resources. These are developed specifically for 3-D graphics performance and function almost like a math coprocessor supplementing CPU performance by directly handling the extreme computing calculations necessary for complex 3-D visualization. Volumetric data such as the size, shape, and depth of a tumor can be depicted in three dimensions, adding rather than subtracting information for the medical practitioner accustomed to seeing this data reduced to the flat format of an x-ray or image scan.

Corvalent’s CorSys family of 4U rackmount systems are optimized for healthcare settings that require 3-D image visualization for improved diagnostics and patient treatment. Benchmarks from Nvidia validate that running PhysX on a mid-to-high-end GeForce GPU enables 10–20 times more effects and visual fidelity compared to running it on a CPU.

This sophisticated medical imaging technology relies on components originally intended for the gamer or maker market. Commercial graphics cards offer some of the strongest performance available; however, it’s their average one-year lifecycle that leaves embedded designers cold. With arduous advance planning, system performance can be maintained for a multiyear, extended medical deployment—but not without causing significant sustaining engineering costs.

Long Life Commercial Options Add Embedded Value

Long-life commercial cards—available from leading global suppliers such as Nvidia—provide an alternative but are potentially unfamiliar to embedded designers because they are relatively new to the market. Long life in commercial terms is perhaps three years and does come at a higher cost than a regular commercial card. But here’s where designers need to think in more traditional embedded design terms: Cost may be an initial factor, but longer life cards reduce operating costs over a long-term medical deployment.

Consider that new software specifications, tools, or compilers may be needed to accommodate a card upgrade. If necessary, software recertification is often more challenging and costly than hardware certification processes. By choosing a commercial card with a three-year lifecycle, developers reduce engineering and design challenges over the system lifetime. In particular, this choice adds essential value in minimizing lengthy FDA recertifications required with each product update.

It’s also important to note that designing with card-based graphics is a commitment – developing systems incorporating Nvidia’s CUDA core and proprietary PhysX technology requires a different skillset than working with the OpenCL technology found in other graphics solutions. Many 3D applications only support PhysX, recognized for its ability to enable simulated image effects without impacting CPU performance. Once designing with PhysX, developers are typically on a long-term path to remain with performance enabled by Nvidia’s GeForce or longer-life Quadro product families.

System Longevity is in the Details

Reliance on commercial components requires planning for obsolescence in the initial steps of the design phase. Early collaboration with manufacturing partners assures the most flexible stocking programs, which can vary extensively according to specific OEM needs, volumes, and requirements. Parts can be purchased based simply on OEM forecasts; or bonded programs can source, stock, and hold components based on the OEM’s purchase order as well as forecast. When more secure partner stocking programs are required—common to components with very short lifecycles—developers may opt for purchase-order-based, noncancellable procurements.

Most importantly, developers and OEMs must explore the requirements for creating a long-term bonded product, asking all the right questions as part of the overall design strategy. Manufacturing partnerships are essential in supporting this aspect of the design process, capitalizing on close supplier relationships to ensure advance notice of end-of-life and ideal strategies for effective, consistent component management.

Blending Commercial Graphics with Embedded Strategies

Three-dimensional imaging is steadily improving healthcare treatment options and is poised to make an even bigger difference as sophisticated graphics-based applications prevail in in clinical decision-making. For developers, understanding both commercial and on-chip options will help optimize long-term performance and bring new value to the complex and competitive medical design process.

Three-dimensional capabilities are not called out in Intel’s embedded roadmap, and new, longer life graphics cards from the commercial realm are filling the gap. While more costly upfront, they have the potential to reduce long-term total cost of ownership and ensure a smooth path for upgrades and continued evolution of 3-D applications in existing systems. With planning and design strategies that capitalize on technical and experienced manufacturer support, medical OEMs and developers can ensure longevity, consistency, and availability of 3-D graphics in long-term healthcare deployments.

Learn how to integrate personalized medicine into your next medical device design at the MEDevice San Diego conference, September 1–2, 2015.

Martin Rudloff is chief technology officer at Corvalent.

[Images courtes of CORVALENT]