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As Industry Grumbles, CDRH Touts its Review Improvements

As Industry Grumbles, CDRH Touts its Review Improvements

While U.S. industry leaders continued to complain about slow FDA device reviews and have been swayed to move a growing share of product development overseas, there’s been a little-acknowledged internal review revolution going on inside CDRH.

CDRH has made improvements on a number of fronts, says Center deputy director for science William Maise. Image by Flickr user moyogo.

That was the message delivered by Center deputy director for science William Maisel to a spring Food and Drug Law Institute update session in Washington, just as lawmakers on Capitol Hill were moving on new user-fee legislation to grant industry additional relief from agency caprices.

Ongoing improvements to CDRH’s premarket review program are paying off, Maisel told the session, describing actions under the ongoing 510(k) revamp that are helping bring greater predictability about data requirements for certain product areas, reducing unnecessary data requests, and implementing new policies allowing more balanced benefit-risk determinations.

“Some of the preliminary data points are starting to point in the right direction,” he said. For example, the 510(k) backlog, which grew from 2005 to 2010, began to drop in 2011 and, in 2012, it continues to go down further.

Although improvements are being seen, Maisel did acknowledge that there is still a lot of work to be done, doubtless raising some skeptical eyebrows among attendees more interested in quick fixes than in small incremental gains over time.

The Center’s Innovation Pathway offers much promise, he said, and “it’s our test bed and our place where we can innovate, try new things and develop new tools. One tool under development is a decision support tool for FDA reviewers to use and evaluate first in human clinical trials coming through the Innovation Pathway. It is a semi-quantitative way to assess decisions and really focus in on the most important issues.”

Maisel said that the decision to allow a first-in-human trial to go forward “is one of the most complicated and challenging ones we make because it is typically based on relatively little information, but we also see the great promise and potential. The tool, which is based on our early feasibility draft guidance will help our reviewers explicitly consider the benefits and risks.”
CDRH is also looking at novel IT tools within the Innovation Pathway, he said, to help promote collaboration during the device evaluation phase. “We have set up a secure online conference center where our device team and industry can work together in a shared space, share documents, exchange communication through that shared space, and have a more collaborative back and forth rather than us throwing something over the wall to industry and industry throwing it back over to us.”

Another area in focus is benefit and risk determinations, Maisel said, and a final guidance issued this year includes a worksheet for reviewers on principal factors to consider when making these decisions.

“We have planned training modules for our own staff,” he said. “We’ll be adding sections within the labeling that summarize the benefit-risk determination, we’ll be making our worksheets available that show what our thinking was, and we’ll be auditing how our review staff and stakeholder like it.”

While the benefit-risk guidance applies to PMAs and de novo devices, CDRH has begun thinking about benefit-risk for postmarket surveillance, Maisel said. “This has been a long standing challenge. In 2012, we plan to produce a vision and comprehension plan that will provide what we suggest as the direction we will be heading. It will be an opportunity to start the dialog and get feedback from stakeholders on what we need or not need to do and other areas where we can move forward.”

What about the Inspection Process?

In reaction to Maisel’s presentation, panel commentator and QualityHub president Timothy Wells said he found it interesting that with all the reinventing occurring at CDRH lately, there is no talk about the inspection process.

“I’m worried,” he said, “that FDA allows a CAPA plus 1, which is a two-day FDA inspection. I’m worried that they do foreign inspections in four days and my clients in the U.S. can have FDA there for 14 weeks. That’s not fair. I know companies that are putting plants overseas to take advantage of the four-day inspection.”

Wells said FDA has had internal discussions about accepting notified bodies’ audits as agency inspections, “and that would be a mistake in my opinion. The notified bodies are the ISO auditors who get paid by the companies and they are very superficial, in my opinion.

“I know FDA is strapped for resources, Wells continued. “I’m just wondering about the resources that they are putting into pre-approval, and how many resources are they putting into the field inspection process? I know we are pulling them in a lot of directions. You may get all these product approvals, but if you don't have good manufacturing practices then that is one of the reasons we have recalls and design issues... And so it is the responsibility of the companies to follow QS and GMPs, but I think it is important also to have good FDA inspections and ask the right questions.”

Additionally, Wells went on, FDA should look into the tools and the training of the investigators. “Some inspections are ‘knock it out of the ballpark’ homeruns and the other half are just leisurely visits,” he told FDLI. “I’m not sure what happened to investigator certification... because having qualified and skilled FDA investigators will benefit everyone and level the playing field.”

Regarding inspections, Maisel responded that “it is simply not possible for us to go out and inspect every manufacturing plant and, with an increasing global economy, we’ve had to strategize about how we are going to use the limited resources we have. We use a risk-based approach to select inspection sites and try to focus on areas where we are most likely to find issues or problems. We have also started pursuing the concept of a single audit program where a single inspection could satisfy multiple regulatory agencies. There would have to be certain circumstances under which those inspections are performed, and it would probably not be available for someone who has a long history of many deficiencies.”

A Business Case for Quality

Maisel also pointed out that, last year, CDRH announced its business case for quality, which is a recognition that slapping someone on the wrist may not be the best approach for getting a quality device. “So we have been meeting with industry stakeholders to try to come up with ways to promote quality systems and practices, which may be separate from compliance actions, because what we really want is quality devices.”

Asked to comment on industry appeals, Maisel told FDLI that there needs to be an avenue to get supervisory input. “We are trying to put more concrete timelines on appeals and we will be coming forward with a guidance document on this,” he said. “The big challenge for companies, I think, is the unpredictability, and the appeals that seem to get lost in a vast morass and a company not having any idea when it will come out on the other side... We end up with somewhere between 30-40% of appeals that are turned over or partially turned over.”

FDLI panel commentator and Hyman, Phelps & McNamara director Jeff Shapiro said that, from industry’s perspective, the appeals process has not been working well and timelines is an issue. The supervisor review process has a problem because there is an inherent conflict-of-interest by having a supervisor reviewing the work of their employees.

“I’ve suggested that there should be an Office of Appeals where it would not be the direct supervisors,” Shapiro said. Another appeals issue is the lack of transparency, he added, and nobody knows how many are pending and how long they take. He explained: “When reforms are introduced, we won’t know if there are improvements unless metrics are developed.” 

FCC Poised to Open Wireless Spectrum for Medical Devices

FCC chairman Julius Genachowski has announced at a press conference today that the FCC will consider opening segments of the wireless spectrum for monitoring medical patients. If approved next week at the FCC's commission meeting it will make the U.S. the first country to allocate wireless spectrum for medical body-area networks (MBANs). The networks will allow information from mobile and wireless-enabled medical devices to be transmitted in hospitals, doctor's offices, and, eventually, even patients' homes. Device manufacturers will be able to streamline their product development and enjoy increased spectrum capacity and reliability.

Currently almost 50% of all patients in US hospitals are not monitored. In his statement Genachowski says that MBANs will enable patient monitoring in real time that is both accurate and cost-effective. “A monitored patient has a 48% chance of surviving a cardiac arrest. Unmonitored patients have a 6% chance of survival.” By allowing for continuous monitoring of patients, MBANs could help doctors respond more quickly in emergency situations and improve overall in-home patient care as well. Genachowski says, “With in-home patient monitoring premature babies could come home a little sooner, a father struggling with heart disease can be aware of his condition and still make his kids' soccer gamer, and a grandmother living alone could stay in her home and keep her independence.”
Current MBAN technology consists of small, wireless sensors that can be attached to a patient's body to monitor vital information, even while the patient is moving about. The sensors allow more freedom for patients that might be otherwise restricted to the bed, while allowing medical professionals to continously monitor patients. “You've heard people talk about the Internet of Things” Genachowski says. “You've heard about machine-to-machine connected devices. Well here's an example of these concepts coming to life. This is a big deal, and we're just at the beginning.”

You can watch the entire press conference below:


Chris Wiltz is the assistant editor at MD+DI

+ Attend MD+DI’s Wireless Connectivity in Medical Devices Conference to find the regulatory, technical and strategic updates needed to break into the wireless medical market.

Women in Medtech: Leslie Saxon's Quest to Shift the Healthcare Paradigm

Leslie A. Saxon, MD is the chief, division of cardiovascular medicine at the Keck School of Medicine of the University of Southern California, and the executive director and founder of the USC Center for Body Computing.

The USC Center for Body Computing (CBC) is a wireless health innovation center. The USC CBC brings together the Keck School of Medicine and USC's world-renowned School of Cinematic Arts with the university’s schools of business and engineering. The CBC creatively synthesizes medicine, engineering, business, communications, and entertainment arts into new paradigms that will innovatively enhance the quality of life, especially for the two billion people worldwide who lack access to healthcare.

Dr. Saxon has completed over 180 publications in various medical journals and is an active member of a multitude of organizations, including the American College of Cardiology, the Heart Rhythm Society, The American Heart Association, and the Heart Failure Society of America. She serves as associate editor of the Journal of Cardiac Electrophysiology. She specializes in the diagnosis and treatment of arrhythmias in patients with congestive heart failure. Dr. Saxon has appeared in many media outlets, including the BBC, the New York Times, CNN, and the Wall Street Journal.

In April, at TEDMED 2012, Dr. Saxon announced the everyheartbeat initiative—a platform to record everyone’s heart rate worldwide. With the data, Dr. Saxon wants to study life patterns, identify disease, solve endemic health problems, and give people control over their own “health narrative.” Everyheartbeat has been covered in publications worldwide.

Here is the video of her TEDMED talk: 

MD+DIWhat led you to become interested in medicine and medical technology?

Saxon: I've always liked fixing things. As a child I had lot's of pets and they would get sick and I'd work with our local pharmacist (our neighborhood's de facto vet) and try to make them better. I became interested in technology later in life, when I began to specialize in treating arrhythmias.

MD+DIWhat important challenges do you see in healthcare in the next 5 years?

Saxon: Maintaining innovation and technical leadership. Providing an indivdualized, efficient service model to patients. Motivating the best and the brightest to go into medicine

MD+DIHow can more women get involved in medical technology?

Saxon: Women in medicine can't avoid technology, and they should embrace it and try to become experts. Think about how technology pervades our general culture. I believe technology, like social media, can help get good health care outcomes and connect and inform patients.

MD+DIAre there barriers for women to work in the medical technology industry?

Saxon: No more than anywhere else. Women can and should lead in this field; it starts with hard work, credibility and an ability to think across disciplines. Women do that in the work place daily.

MD+DIWhat advice would you give to people interested in pursuing a career path similar to yours?

Saxon: Strive for excellence in your core the best, learn from whomever you can. Don't expect balance in all phases of your life, excellence and balance are natural enemies. Enjoy it along the way. 

 Brian Buntz is the editor-at-large at UBM Canon's medical group. Follow him on Twitter at @brian_buntz.

Using CFD to Gain Insight into Medical Device Designs

A few examples where CFD has played an important role include:

  • Optimize the exterior shape of intravascular devices to improve their performance and minimize their disturbance on the surrounding blood flow field.
  • Identify regions of flow recirculation, remove unneeded flow volume, and hence reduce the potential for blood clot formation within your device.
  • Improve the coating uniformity on devices such as cardiovascular stents by modeling and refining the spraying technique.
  • Predict the distribution and depth of deposition of inhaled drug particles in the human lungs using CT-scanned images of the lungs.
  • Assess the change in drug concentration with time for an implanted drug-coated device based on the local tissue properties and adjacent fluid environment.

CFD is also gaining recognition as a valuable tool for supplementing test data needed for regulatory submission and approval. An FDA/NHLBI/NSF-hosted workshop on computer methods for medical devices held in 2011 is one example of the effort underway to fully leverage the benefits of numerical simulation. This conference presented advances in both solid and fluid mechanics modeling of cardiovascular and orthopedic devices and the associated validation results. Future conferences are aimed at expanding both the physics studied, such as including electromagnetics, and the fields-of-use. The insight gained from using CFD, when combined and validated with experimental data, provides a strong technical foundation upon which sound design decisions can be based. Focused CFD efforts enable rapid consideration of design alternatives, explore performance across a range of operating parameters, and ultimately help reduce the overall development time and cost in bringing a new technology to the medical marketplace.

CFD provides both detailed flow-related information and overall performance assessments that can be used to guide the direction of product development. 

CFD provides both detailed flow-related information and overall performance assessments that can be used to guide the direction of product development. Such numerical design iterations can often reduce the number and cost of expensive and time-consuming prototype fabrication and testing. Using CFD analysis, manufacturing processes that involve fluid flow can be optimized from both a quality and cost standpoint. For instance, if your process involves the controlled curing of a polymer coating to promote good adhesion with the substrate, one can model the impact of local air temperature and flow conditions on the rate and uniformity of the curing process. The technology is also promising for simulating human physiological flows that interact with devices or affect drug-delivery performance; obtaining detailed measurements for such flows is often difficult, time-consuming, and expensive to measure using animal or other physically-representative models.

Many biomedical applications involve fluid flow and heat/mass transport in a device or within the human body. Some examples include blood pumps, artificial heart valves, blood oxygenators, filtration devices, catheters, tubing, aerosol drug delivery, and diagnostic equipment. Such CFD models can include the effects of magnetic fields, gas transport, multi-phase flow, deposition of particles, deformation of solid regions surrounding the fluid, and biochemical reactions. CFD analysis offers details of fluid velocities, pressures, solute or particle concentrations, temperatures, fluid stresses, and heat/mass fluxes throughout your entire device.

These computed flow-related parameters can be displayed in different formats—including color-coded images—revealing the fluid-related inner workings of your device. CFD is an excellent tool for conveying the functionality of your new device to others, including your management and development team, future customers, and regulatory agencies. As part of an analysis, engineers can alter model geometry, boundary conditions, or material properties to determine the effects on the system under study. As a result, CFD is well suited for conducting parametric studies, making it possible to evaluate more design alternatives than with traditional build-and-test methods, thereby allowing for faster performance optimization and significant reduction of design cycle time.

While experimentation using physical and animal models is needed to demonstrate the actual performance of a new device, it has some important limitations that explain the increasing emphasis many device manufacturers are placing on computer simulation. Experiments take a long period of time to perform, are expensive, and, in certain cases, may involve risks to animal or human subjects. For these reasons, device manufacturers are turning to computer simulation to evaluate the relative performance of various design alternatives over the full range of intended use in an effort to further ensure the safety and effectiveness of their products.

Another problem with physical testing concerns the limited quantity or accessibility of the data, which are obtained only at those locations where measurements can be made. Computer simulations, by contrast, can provide calculations of as many relevant parameters, and in as many locations, as the analyst requires. CFD models provide detailed flow information and insight even in regions where physical measurements cannot be made.

CFD benefits include the abilty to:

  • Analyze. You can graphically visualize any number of cause/effect relationships to improve device performance and effectiveness. With a CFD model, you can easily change and assess the impact of different fluid properties or composition as well as the boundary conditions (i.e. flow rate, pressure and temperature) on your device’s performance. This is particularly useful when evaluating your device over its intended range of use.
  • Optimize. You can quickly evaluate design options prior to laboratory testing to save time and money while demonstrating product viability and performance. With detailed flow-related information, such as local speed, pressure, and temperature conditions, one can make design refinements that can be critical in balancing design trade-offs and achieving the intended performance goals. In a blood oxygenator, for example, gas transfer increases as the blood shear rate adjacent the gas transfer surface increases. However, it is critical to stay below shear rates that could cause blood cell damage or lead to platelet activation. Using CFD, both the surface blood shear rates and gas transfer can be predicted and the flow path geometry adjusted to optimize the overall device performance.
  • Understand. You are able to evaluate implications of changes in design or process variables to rapidly gain a wider knowledge base. Having the ability to see the flow patterns within your device over a broad range of operating conditions gives you the ability to determine the direction for your design changes and fully advance your technology.
  • Troubleshoot. You can understand and diagnose problems quickly prior to confirmatory experimental testing. If unforeseen performance issues occur when moving from bench testing to in vivo evaluations, such as platelet deposition, CFD analyses can prove invaluable in helping to uncover the source and guide the direction for resolving the issues. The CFD simulations can identify both high and low shear stress regions where platelets could be activated and deposited. Geometry changes can then be made to eliminate such regions and the resulting performance confirmed through new in vivo tests.
  • Reduce time-to-market. You can speed product development by modeling multiple scenarios, thereby ruling out unsuccessful attempts before conducting time-consuming laboratory tests—ultimately compressing your development cycle. Key here is the efficient use of your company’s resources. The goal is to bring safe, high quality, and well-designed devices to market quickly. Fully leveraging the capabilities of CFD to direct the development path and support the experimental testing is a prudent means to achieving this goal.


In summary, CFD offers your engineering teams the ability to visualize and better understand the key design trade-offs affecting the performance of you new design or manufacturing process. With this knowledge, they can select a preferred design and then navigate through bench and in vivo testing that is needed to validate the modeling methods and confirm the device’s performance. The ultimate goal is to efficiently deliver a new product that has a solid technical foundation and, as a result, will function reliably and effectively when used clinically.

Case Study: Cleveland Clinic Right Ventricular Assist Device (RVAD). One of the keys in successfully applying CFD is to clearly define your analysis objectives. For example, the research team at the Cleveland Clinic was developing a new centrifugal blood pump for right ventricular support (Figure 1). Key to the success of this new pump was achieving the desired hydraulic performance (i.e. pressure increase), limiting the peak wall shear stress to minimize the potential for blood cell damage, and providing uniform wash-out to reduce the likelihood of blood clot formation in re-circulating flow regions. Early in the program, CFD studies of the pump incorporating a standard volute design, one that is in-line with the pump’s primary impellers, showed good values for hydraulic performance and wall shear stress levels. However, the time the blood resided within the pump (i.e. blood residence time) was significantly increased in the lower regions of the pump. 

Figure 1. Color contours of velocity in stationary frame on pump rotor. On the left is the standard volute design, while the image on the right depicts the offset (lowered) volute design. 

To address this flow non-uniformity, the Cleveland Clinic team proposed a lower, offset volute design. The resulting CFD analyses for the new volute design provided a significant increase in flow between the inner rotor and the outer pump housing as the blood flowed from the primary impellers to the volute. This enhanced washout of the lower rotor surfaces yielded a 3× improvement in the overall uniformity in the pump’s blood residence time (Figure 2). This significant reduction in average residence time provides a larger margin of safety related to the pump’s potential for blood clot formation. With the offset volute design, hydraulic performance and wall shear stress values were still within the desired range. In vitro experimental studies, via hydraulic performance testing and dye wash-out studies, supported the CFD predicted pump results.

Figure 2. Color contours of residence time, centerline plane cut. As was the case with figure 1, the image on the left shows the standard volute design, while the image on the right shows the offset (lowered) volute design. 

In summary, CFD simulation was used to uncover and highlight regions for pump design improvements. It was then used to assess the impact of design changes that were confirmed experimentally. The CFD analyses revealed flow details throughout the pump that were difficult to observe experimentally and helped verify the benefit of the new offset volute design.

Note: SimuTech group used both ANSYS-Fluent and ANSYS-CFX to perform the CFD analyses in support of the Cleveland Clinic’s right ventricular assist device development. 

Mark Goodin is an experienced CFD consulting engineer at SimuTech Group (Hudson, OH). He specializes in CFD simulation of medical devices with particular expertise in cardiovascular device simulation and product developmentHe holds a master's degree in engineering from Massachusetts Institute of Technology and a bachelor's in engineering from University of Illinois at Urbana-Champaign. 

Fostering Medical Device Manufacturing in the Land of the Maple Leaf

What the medical device hub of California is to the United States, Ontario is to Canada. With approximately 700 companies and 22,000 employees, the province's medical device industry is attracting increasing interest for its potential to provide innovative medical technologies to patients and clinicians, create jobs, and attract investment. Still in its early days of discovery, Ontario's medtech sector will continue to develop and evolve, says Stephen Dibert, past president and CEO and current special advisor to Medical Devices Canada (MEDEC; Toronto), a voice for the medical device industry in Canada.

The largest concentration of medtech companies in Canada, Ontario is home to approximately 65% of the country's medical device industry. While it is dwarfed by its giant medtech neighbor to the south, the Ontario medical device hub boasts a diversity of companies that develop and manufacture a variety of diagnostic, imaging, surgery, cardiovascular, oncology, orthopedic, neurology, urology, and gastroenterology devices. Serving such industry giants as 3M, Abbott Point of Care, Edwards Lifesciences, Medtronic, Johnson & Johnson, and St. Jude Medical are literally hundreds of supplier firms offering everything from materials and electronic components to contract manufacturing, design, sterilization, and testing services.

And as one of North America's most concentrated biomedical hubs, the greater Toronto area alone boasts 60 hospitals, 37 medical institutions, eight universities, two major medical schools, and tens of thousands of healthcare professionals. Given the local medtech industry's bountiful resources and growth potential, the province's medtech leaders have their work cut out for them for many years to come.

Medtech Advocates
"Ontario has a well-deserved reputation for researching, developing, and commercializing medical technology," Dibert remarks. "Several Ontario companies have proven successful, such as Baylis Medical, a global supplier of high-technology cardiology, pain-management, and radiology products that maintains a research and manufacturing facility in Mississauga."

Despite such success, the early days of the province's medical technology sector were characterized as unregulated and unorganized, Dibert notes. To rectify this situation, medical device industry leaders created MEDEC 40 years ago to represent the sector's interests. Ever since then, the association has been actively involved in advocating for the industry's interests. One of MEDEC's initiatives, according to Dibert, is the Canadian Medtech Manufacturers' Alliance (MEDEC-CMMA), which resulted from a merger with the Ontario-based Trillium Medical Technology Association. MEDEC-CMMA, in turn, supports the development of new and established small-to-medium size medical device companies in Ontario.

"MEDEC has strong, working relationships with several organizations in Ontario," Dibert says. "With approximately 70% of MEDEC member companies located in Ontario, the association is constantly looking to add Ontario-based companies as members." As part of its activities, MEDEC also supports and participates in the work of the Medical Device Innovation Institute in Ottawa, the Ottawa Centre for Research & Innovation, and Canadian Surgical Technologies and Advanced Robotics. In addition, it collaborates with several Ontario biotechnology cluster consortiums and has a close working relationship with the Health Technology Exchange (HTX).

The role of HTX is to support the efforts of emerging and established Ontario-based companies to develop, produce, and commercialize medical imaging, healthcare IT, wireless health, and other medical device technologies, Dibert says. Among its functions, HTX funds projects that promote partnerships among such stakeholders as small, medium, and large enterprises; academic and healthcare institutions; investors; and granting agencies. In addition, it maintains such initiatives as the Health Technology and Commercialization Program (HTCP), a funding program made possible through the Ministry of Research and Innovation. "The HTCP," according to Dibert, "was specifically designed to strengthen Ontario's medtech cluster. Similar programs will be offered in the future."

MEDEC has also partnered with government bodies to promote the medical device sector in Ontario. For example, in 2011, it helped create the Business Sector Strategy for Medical Technology together with the Ministry of Economic Development and Innovation. For its part, the federal and provincial governments foster the growth of the medtech sector by offering a host of tax incentives, including a federal R&D tax program, the Ontario research and development tax credit, the Ontario innovation tax credit, and the Ontario business-research institute tax credit.

And these tax incentives have not gone unnoticed. "It's fairly well known that Canada has a very good tax incentive program," says Ella Korets-Smith, global brand manager at Nordion (Ottawa, ON). "In the past, we have participated in research activities by taking advantage of tax incentives offered by Canada and Ontario."

Nordion--a MEDEC member company through the Nuclear Medicine Alliance, an affiliate member of MEDEC--is a textbook example of a company that has helped put Ontario's medical device sector on the map. The company, according to Korets-Smith, started out as Atomic Energy Canada Ltd., a Canadian government enterprise. In the 1960s, its scientists developed a technology for using the radioactive isotope cobalt 60 to irradiate products to eliminate microbes. Servicing multinational contract sterilizers as well as medical device OEMs that employ its irradiators to sterilize their own products, Nordion has developed a technique that has come to be used in Canada and around the world to sterilize single-use medical devices in final packaging.

Training Future Medtech Experts
"For everyone in the medical device industry in the region, it's a priority to involve youth and the student population to learn about the applications of nuclear technology pertaining to sterilization and the use of cobalt 60," Korets-Smith says. "To that end, the company engages in collaborative projects with the University of Ottawa Heart Institute to further its medical isotope business and has also worked with the University of Quebec in Laval, where the company's Canadian Irradiation Centre has been located for the past 25 years." Offering private and academic sector partners a facility for gamma irradiation research, training and services, the center concentrates on the science and practice of sterilizing medical devices.

Playing a prominent role in educating and training new generations of medical device professionals is the Medical Devices Innovation Institute at the University of Ottawa (MDI2), the mission of which is to focus on medical device discoveries, development, manufacturing, marketing, commercialization, and utilization in patient care. "Of course, to do that, you have to train experts in medical devices," says MDI2 director and CEO Tofy Mussivand. "That's one area that we focus on, not only at one hospital or one university, but we share it with industry and many other institutes." In addition, the institute helps industry with navigating the medical device approval process in a variety of global regions, from Canada and the United States to Europe, Japan, China, and India.

Currently, the Institute is working on the development of approximately 20 technologies, among them an artificial heart and a portable DNA detector. All in all, the institute is collaborating with other organizations on more than 150 technologies, including cardiovascular devices, technologies for infection and bacterial detection, monitors, imaging equipment, orthopedic devices, robots, and surgical tools.

Medtech: A Strategic Priority
Yet despite its indisputable potential, Ontario's medical device sector--like that of Canada as a whole--faces a plethora of challenges, Mussivand emphasizes. Foremost among them are the country's lack of medical device expertise and skills; lack of a strategic focus on medical device development and manufacturing; insufficient incentives to attract and retain industry; and a corresponding lack of both public and private investment, especially at the development stage. "For various reasons, our medical device industry is not working at capacity in terms of development, commercialization, and marketing," Mussivand says. "In fact, among industrialized nations, our medical device development and export activities are nearly in last place, just before Norway."

Many regions of the world, including the United States, Europe, Japan, and China, have placed a higher strategic priority on developing medical devices than has Canada, according to Mussivand. To reverse this trend, MDI2 and medical device professionals are pushing politicians and decision makers to expand Canada's contribution to the global medical device sector. "For example, no company is going to produce medical devices just for Canadians," Mussivand says. "Our population is small, and the market is not large enough to sustain a medical technology sector strictly for domestic use. However, that should not be the reason that we are not a medical device leader. Switzerland, which has been the first country to develop a variety of medical device technologies, is smaller than Canada."

Part and parcel of Canada's low status as a designer, developer, and manufacturer of medical device is the difficulty startups face in funding new projects. "In terms of funding and investment opportunities, my experience shows that when you want to develop technologies and you need funding, you mainly have to go outside of Canada to bring capital in from outside," Mussivand notes. "I think that this needs to be changed."

Nevertheless, there is movement to rectify this problem, Mussivand adds. For example, MDI2 has been organizing medical device summits in the last three years in order to bring professionals together from across Canada from various disciplines. Invitation-only events, they have attracted great interest, demonstrating that there is interest from all sectors--not only from hospitals and universities but also from industry and government--to bolster the country's medical device industry. "Nearly the entire medical device industry supports our initiatives and has been working with us not only to advance these technologies but also to set medical device development and manufacturing as a strategic priority for Canada," Mussivand says.

As for Ontario itself, the province will continue to be the largest region for the medical device and biotech industries in Canada, according to MEDEC's Dibert. Most medtech companies in Canada are located in Ontario, and the province has demonstrated in word and deed that it is willing to support the industry. "The medical device manufacturing sector is a win-win industry for Ontarians and Canadians," Dibert adds. "Along with producing better patient outcomes, investments in innovative medical technologies can also lead to long-term cost savings for the healthcare system, while contributing to more jobs and a stronger economy in the province and in the country as a whole. We see nothing but growth for the industry in the future."

Using Only the Power of Her Mind, Paralyzed Woman Controls Robotic Arm

An NIH-funded trial is investigating the use of the BrainGate neural interface system, which would enable paralyzed patients to control a robotic arm solely with the mind. In a recent study document in Nature, two patients with tetraplegia were able to use the system to make complex reach-and-grasp movements. To accomplish that feat, neurosurgeons implanted into the motor cortex recording devices that are about the size of a baby aspirin. The electrodes were then able to record the patients' neuronal signals that fire when the patient intends to move. The resulting impulses are translated into the movement of an external robot. 

Brian Buntz is the editor-at-large at UBM Canon's medical group. Follow him on Twitter at @brian_buntz.

Medical-Grade Polyurethanes, from Wound Care to Permanent Implants

Tony Walder, manager of technology, thermedics polymer products, for The Lubrizol Corp. (Wickliffe, OH) will present "Medical-Grade Polyurethanes, from Wound Care to Permanent Implants" at the MD&M East conference program on Monday, May 21. Lubrizol specializes in additives, ingredients, and compounds optimized for the healthcare and other industries.

MPMN: What characteristics or properties of medical-grade polyurethanes make them potentially more desirable for certain applications than other polymers?

Because of such characteristics as versatility and biocompatibility, polyurethanes are suited for use in a range of medical applications.

Walder: Polyurethanes feature characteristics that may be useful in a variety of medical application, including biocompatibility, processing ease, strength, and versatility. Available medical-grade polyurethanes currently range from soft elastic Shore durometer 62A to rigid glass-filled versions featuring a flexural modulus of 2,200,000 psi. Because of the materials' versatility, polyurethanes can compete with silicones as well as metal replacements.

Soft elastomeric polyurethanes specifically are known for their strength and can be up to four times stronger than other elastomers, such as silicone. This strength allows for the development of tubing with thinner wall thickness. A tube can have the same outside diameter, for example. But because the wall is thinner, the inside diameter is increased for improved fluid flow.

Furthermore, biocompatibility of medical-grade polyurethane also means that it may be useful in implants for different areas in the body, lasting from minutes to the lifetime of a patient. The versatility of polyurethanes allows for various characteristics to be highlighted as required for the application. Some of these characteristics include abrasion resistance, softening, chemical resistance, and diffusion rates of moisture or gases.

MPMN: What processing methods are optimal for producing polyurethane parts or devices?

Walder: Thanks to ease of processing, thermoplastic polyurethanes may be processed using the common melt techniques of extrusion and injection molding. The extrusion process can be employed to make films, sheet, single-lumen tubing, profile tubing, and multimaterial tubing, among other products. Injection molding, on the other hand, is suited for building complex polyurethane parts of a device. To a lesser extent, thermoplastic polyurethanes can be dissolved in a solvent to coat a device or to create thin-film components such as balloons. Many polymers can be dissolved and cast into thin, complicated components as well.

MPMN: What's next for medical-grade polyurethanes?

Walder: Lubrizol has many active programs aimed at developing unique polyurethanes that may be useful for medical devices. Areas of interest range from expanding existing product lines to meet the demands of new devices to developing new lines of materials.

A Near-Term Look At Medtech Investing

Bill Evans
Bill Evans, founder and president of Bridge Design

That quote sits in stark contrast to a fact apparent to anyone close to medtech over the last decade or so: the costs of bringing products to market have escalated significantly. This state of affairs has been quantified and publicized in a survey titled FDA Impact on U.S. Medical Technology Innovation by Josh Makower, a medtech entrepreneur. “The average cost of taking a product through 510(k) clearance is $31 million, and the average cost of getting a product through PMA…is $94 million (excluding reimbursement and sales/marketing activities),” Makower reports. “For U.S. companies, these mounting costs are unsustainable in a venture-backed industry where [fewer] than one out of four medtech start-ups succeeds, 50% of all reported exits are less than $100 million, and the total pool of available investment capital is shrinking.”

These source articles reveal two seemingly contradictory trends over the last decade. On the one hand production costs have risen significantly; on the other, venture-investing medtech returns have outperformed tech investments at a time when it seemed that all the VC action was with Internet-related plays. Both are true. Digging deeper reveals how various investors, entrepreneurs, and other stakeholders have reacted to these changes. This exploration in turn uncovers what the next three to five years of medtech investing may look like.

Structural Changes

A survey of historic financial data will not necessarily show today’s medtech entrepreneurs where their funding will come from in the near future and what the next set of investors is likely to care about. At least four structural changes in the market account for this state of affairs:

• Shifts in investment amounts, timing, and risk appetites of venture money sources.
• Increasing regulatory and reimbursement pressures.
• Globalization of medtech funding and newly emerging markets.
• Increasing emphasis on the overall cost of outcomes in a world of escalating healthcare costs.

The good news is that medtech investment insiders all seem bullish on the industry. Robert Curtis, CEO of Respira Therapeutics and a seasoned medtech chief executive with 10 start-ups, notes: “There have been some great successes in the device industry; it’s probably one of the most resilient of the regulated industries in the U.S.” Makower hopes “that brighter days are ahead. Medtech is a good place to invest in the future, but those involved must be exceptionally selective.” Reports on the latest medtech funding numbers support this optimism, showing an increase of approximately 33% in the first quarter of 2012 compared with the same period last year.

Of course, investors of any kind have always been selective, but anyone who has tried to raise money over the last few years has felt the chill wind of this exceptional selectivity. It affects who funds entrepreneurs and when they’re funded, and it creates bigger hurdles for a product to overcome.

Where Will VC Money Come From?

The current environment has scared a lot of investors off, changing where the early seed money is more likely to come from. Casey McGlynn leads the life sciences practice of the law firm Wilson Sonsini Goodrich & Rosati (Palo Alto, CA), which over the last two years helped privately raise about $1 billion for medical device companies. “Our industry has spent a lot of time analyzing and complaining about the performance of FDA, and rightfully so,” he notes. “Congress has heard us, and the institutional funds that invest in VCs also heard us, and I think we scared them about the difficulties our industry is facing.”

Compounding this regulatory tightness was, of course, the global financial meltdown. Curtis says that medtech started to feel the effects a little before 2008. “The financial market started to get constipated; money wasn’t flowing well. When that spigot got cut off, the funds looked at what they were doing and instead of investing in early stage start-ups they invested in later rounds of more mature start-ups because they could foresee getting to an exit earlier. On top of that came a shutdown in the IPO market, so for the most part, device companies couldn’t raise money from the public over the past few years. The sole exit has been to be purchased by a big medical device company.”

These pressures have lead VC firms to become more specialized. “Today’s VC firms don’t make the mistake of dabbling in areas in which they are unfamiliar,” says Steve Halasey, vice president of the Institute for Health Technology Studies (Washington, D.C.), which supports independent research and educational activities focused on medtech. “Firms have become increasingly specialized, even to the point that medtech VCs who have a strong interest in a sector such as cardiology might not deal in another area such as IVDs. For the investors who know what they’re doing, there’s no question that the returns in the medical device area have been very good.”

Regarding investor returns, Jonathan Wyler, a principal in SV Life Sciences (Boston) who specializes in medical devices, says, “On average in medtech it’s seven years until an exit, but many of the successful companies of recent years have taken over a decade to reach acquisition. This is a very long time horizon, and hence investors have to support the organization for a longer period, which means considerably more capital. To manage a venture fund to a three-times return, and because returns on successful medtech investments are generally not as high as in tech, it becomes critical to manage loss ratios by identifying the losers more quickly, manage to get your money back on as many as you can, and to avoid expensive investments with binary outcomes.”

This approach makes it harder for VCs to invest early in companies where outcomes are inherently less certain and holding periods are longer. “VCs are not running to invest in very early stage companies,” Wyler says. “Most are buying in later and looking for attractive economics, and much less frequently making an exception for only the most [distinctive] earlier stage opportunities with the very best teams.”

On top of these pressures VCs are feeling a chill from the institutional investors when they go out to raise their own new funds. “The risk-return in medtech relative to the substantial capital needed to get to an exit is different from the tech world,” Wyler says. “Institutional fund managers who are investing in many different asset classes are generally not into the detail of a particular product category or science, but [they] do recognize the headline level themes—depressed markets, challenges with FDA, healthcare reform, acquisitiveness of consolidators, and so on—and often generalize such issues to the entire medtech space. This complex environment has given large institutional funds pause in terms of investing in healthcare. However, these regulatory and other hurdles do create value-generating barriers, and with the right experience and expertise, such risks can be managed to create long-term value in a manner that is not typically present in the tech world.”

Historical returns from VC healthcare funds “are more consistent over time” than the high-profile IT and software successes, according to Rich Ferrari, cofounder of De Novo Ventures (Menlo Park, CA). Formerly CEO of two successful VC-backed, publicly traded medtech companies, Ferrari adds: “There are bubbles in technology, consumer, and electronics. When you look at healthcare, over the last decade or so, it really doesn’t have bubbles. It has a consistent gradual increase. Some returns in IT and technology look good, but they are small in numbers compared with the thousands of companies that are funded. So actually, healthcare does have a better [internal rate of return]. But the environment today for raising money as a healthcare fund is difficult. The institutional investors in VC funds look at these headline big IT returns and their 10-year return in healthcare, and they are not pleased with it.”

Angels ‘Alive And Well’

These twin pressures on the investment dollars available for VCs, both into and out of their funds, have meant other sources of funding have increased, especially for early-stage ventures. “Angels are alive and well,” says McGlynn. “At the earlier stages of a company they’re more active in putting more money in than ever before. In many ways the Series A venture financing is now being done by angel investors. To lure a five-star VC firm and build that first syndicate you really need to have a great animal beta, a great prototype, and in some cases even credible human data. We are doing a lot of early-stage work with angels and what you might think of as micro-venture capitalist funds. They’re slightly more institutionalized than just an individual investor.” Examples of very early investors, McGlynn says, are Aphelion Capital, X/Seed Capital, and MedFocus Fund. Angel groups include Life Science Angels, Angels Forum, and Bank of Angels, he says.

Another group of angel-like investors, family funds, is gaining momentum, particularly in Europe, Curtis says, “where the family funds model is more advanced; and in the Far East, places like Singapore, which has some fairly sophisticated investors.” McGlynn has also seen Asian sources of funding rise: “We see companies looking for capital in Singapore and other Asian countries where they can set up R&D at a low price, get grants from the government, and raise money from what you’d think of as offshore angel investors.”

Corporate Venture Investing

“There’s a resurgence in corporate venture capital,” says Curtis. “In the 1980s a lot of companies like Medtronic, Pfizer, and Boston Scientific invested in deals directly from their balance sheet. They then retrenched, but recently I have noticed that more corporations in pharmaceuticals as well as medtech have formed venture funds, or have partnered with experienced funds to invest in start-ups. These companies are beginning to invest broadly. As an example, Pfizer has invested in a couple of medical device deals that could replace pharmaceuticals in some areas. One is NovoCure, which uses a device for glioblastoma therapy. Novartis has looked at medical device deals. So far, not many of these funds are willing to invest in early stage deals, but at least the corporate interest has increased.”

The list of device companies with recently established corporate venture funds includes Covidien (August 2008), Abbott (June 2009), Baxter (July 2011), and Philips Healthcare (August 2010). These companies join the parade of existing players like Novartis, Medtronic, St. Jude, and Kaiser, all of which have longstanding venture investing arms. “The corporations in general have really stepped up to be major funders of new medtech companies, all the way down to the seed level,” notes McGlynn. “The business development people at these large medtech companies are very sophisticated people; they do their homework, they’ve got huge domain knowledge in their specialist area. They’re a bit more targeted than the venture capitalist. I think they’re under a tremendous amount of pressure to help find and fund the best new projects, and the exit might be a little bit earlier to the corporate investor than the venture capitalist. We just started a company with really exciting technology, and Covidien was the first investor.”

Other Funding Sources

“European venture funds are interested in investing in medtech companies that have a CE mark and want to commercialize in Europe,” McGlynn says. “So these late mezzanine rounds where we used to have a lot of interest from domestic VCs now have a lot of interest from international VCs.” He also notes that grants are a big source of capital today. “There’s a lot of money through DOD, SBIR, and NIH grants, as well as from foundations with an interest in the area a new venture is addressing.”

Curtis has seen a change in attitude about grants. “I think government grants are going to be increasingly important,” he says. “For the past 10 years, the venture community looked down their noses at device companies that received grants. Grants are attractive from a founder’s standpoint as they are non-dilutive, but it sets a government-financed research culture that the VCs find not very entrepreneurial. The state of Texas, for instance, has made two very large funds available for grants to Texas-based start-ups. Some states realize the benefits of doing this and will be able to stimulate their entrepreneurial economy.”

Regulatory Climate And Reform Hopes

Makower hopes for a new stable FDA environment because of these three changes:

• MDUFA guidance will be modified to incorporate key stakeholders feedback.1
• This legislation then passes, improving the efficiency and predictability of FDA.
• When it does pass, FDA quickly and vigorously pursues the changes needed for it to take effect.

Ferrari is optimistic about the near future. “I think we see that FDA is very serious about trying to make appropriate changes to streamline the system,” he says. “There’s a lot of effort going on between AdvaMed and other lobbying and industry groups working with FDA. I think we’re going to see improvements. It may still take us two to three years, but there is a tremendous amount of pressure from Congress to change the system. I think politically it’s going to happen.”

Advice To Entrepreneurs

Makower sums up advice for those device companies currently looking for early venture cash: “You need to be aggressive [and] resilient, and if you believe in what you are doing, don’t give up. If you have a choice of projects, choose one where the regulatory path is clear.”

Keeping your venture lean has become the new mantra to allow sparse investment dollars to go further. “Don’t quit your day job until you’ve made some progress with your new product,” Curtis advises entrepreneurs. “Make sure that every dollar goes to moving the product forward in the early days to get to a major milestone, like first-in-man. Then you’ll be better able to go out and raise more money at a decent valuation. Entrepreneurs should look at being entrepreneurial within the context of what they are already doing, and find other people who are interested in doing virtual incubation, making progress working evenings and weekends. There are some very smart and dedicated people in this industry. I think they’ll find new ways to do things faster, cheaper, and better.”

Ferrari also counsels a lean approach. “If you are going out to raise a seed or early round, the best validation to raise money is if you’ve already got some angel money or put some of your own money in,” he says. “If you haven’t done that, [then] when you pitch you’ve got to have a well-thought-out game plan. It might be best to approach the problem in small bites. For example, instead of asking for $10 million now, just raise $2 million, set up some very tight milestones, and run an efficient operation. Mitigate the risk of the program and then go on to raise the next piece. Inch your way along until the risk gets wrung out of the program. That’s a very efficient way to run a company, and the way we used to run them a decade ago.”

Wyler believes today’s leanness means something different than before. “I think it’s much harder to be the cliché engineer in the garage,” he says. “It’s a lot tougher today to go on your own as a first-time entrepreneur. Team up with proven people with a proven process. Connect with the incubators, connect with the successful entrepreneurs who have relationships with investors, and recognize that fundraising is likely to take longer and require more creativity and persistence than in the past.”

Demographic trends still make the medical device business an attractive investment opportunity. “At the end of the day,” says Ferrari, “I still believe that healthcare is an important component to have in an asset allocation model because you can’t get away from the fact that the population of the world is growing older faster than at any other point in time. And we need healthcare. We want the best devices and drugs, and to go to the best medical centers. This is not going to change.”

“Be tenacious,” McGlynn advises medtech investors, because the industry is still healthy. “We continue to close a lot of early-stage rounds. This is a great age. There are some incredible ideas out there. I’ve seen that entrepreneurs need to be leaner. They’ve understood they have to move their products farther before they’re going to be eligible for venture financing. So I’m very bullish about the industry. For those who are tenacious and have a great idea, there’s going to be money.”


1. Medical Device User Fee Amendments of 2007 expire September 30, 2012. Congressional committees had planned to move legislation by April 2012 and have the new measures passed by both the Senate and House by early summer.

Bill Evans is founder and president of Bridge Design (San Francisco), a medical product development company. He can be reached 415/487-7100.

Modification of Silicone Chemistry and the Impact on API Release Rates

Brian Reilly, product director, healthcare materials, at NuSil Technology (Carpinteria, CA) will present "Modification of Silicone Chemistry and Its Influence on Release Rates of Active Pharmaceutical Ingredients (APIs)" at the MD&M East conference program on Monday, May 21. Serving the medical device and other industries, NuSil focuses exclusively on silicone technology and related process development.
MPMN: What features or characteristics of silicone make it desirable for drug-delivery applications?

Reilly: For about 60 years, silicone has been used as a raw material for healthcare applications; it has been used for more than 20 years as a raw material for use in drug-delivery applications and combination products. Silicone is highly chemically stable and biologically inert. In addition, the cured silicone matrix has a high degree of free volume, which facilitates compounding in a variety of soluble APIs. It is this free volume that allows APIs to diffuse through the matrix and be released through the surface of the part or device.

Nusil Silicone API
Various obstacles, including crosslink density and reinforcing silica, impact API permeation through a cured silicone matrix.

Silicones also offer a host of options in terms of physical states and chemistry, such that end-users, in turn, have many options in regards to processing methods, which include extrusion, liquid injection molding, and transfer molding. Silicone formulations can be customized in a variety of ways to facilitate a specific process of fabrication while achieving key mechanical and drug-elution properties as well. Application examples include antimicrobial catheters, contraceptive intravaginal rings (IVRs) and intrauterine devices (IUDs), pacemaker leads with an antiinflammatory active, and transdermal skin patches that range in application from treating high blood pressure to pain management.

MPMN: What factors must medical device companies take into account when planning to incorporate APIs into a silicone system?

Reilly: Initially, medical device companies should determine whether they have the appropriate facilities and quality systems to work with APIs. On a basic level, they should understand the API in question: Is it solid, liquid, or crystalline? How soluble is it in silicone? In combination with loading level, these factors will dramatically influence the types of mixing equipment that will be needed to compound the API into the silicone, as well as the degree of difficulty to do so. Is the API sensitive to light, temperature, or moisture? Will it react with other chemicals? Answers to these questions immediately impact storing and handling of the neat API and heavily affect processing conditions and finished product storage as well.

Regarding temperature stability, many APIs are sensitive to elevated temperatures, while most silicone elastomers require elevated temperatures to cure. This question of temperature compatibility must be answered but, to do so effectively, a customer must also have the analytical capabilities to identify and assay the active and any degradation products the manufacturing and curing processes may cause. In addition to extensive capabilities for identity and purity determination, a medical device company must also have the means to conduct elution testing and content uniformity testing. Lastly, there's inhibition. If a company is hoping to employ a process and design that relies upon the compounding of an API into a two-part platinum-catalyzed silicone, it will first need to determine if there are any incompatibilities between the platinum catalyst and the API. Platinum catalysts are very sensitive to many different elements and chemicals; therefore, it's possible that the API could inhibit or kill the catalyst. In such an instance, other cure chemistries will need to be considered, which could dramatically alter the process design.

MPMN: What challenges does the integration of APIs into a silicone system present for medical device applications?   

Reilly: The main challenge is simply stated but often complex to overcome. Applications that depend on a silicone elastomer to function as the platform for the delivery of an API have basic development goals:

o    Achieve a method for compounding the API into the silicone that results in good content uniformity without causing degradation of the API
o    Achieve a formulation that delivers a cured part with the necessary mechanical properties
o    Achieve a formulation that yields a cured part with the specified API release rate
o    Achieve a formulation that may be readily processed

What makes these straightforward goals so challenging is that they are often competing with each other. Certain formulary adjustments intended to facilitate a release rate can result in diminished mechanical properties. On the most basic level, the moment the silicone is loaded with an API, its rheology changes--which can often impact processability--and mechanical properties are diminished. Once the product is successfully developed, the next challenge becomes determining the stability of the formulation on the shelf over months and years. Will the API eventually degrade the cure chemistry of the silicone, or will the silicone chemistry slowly degrade the API? Such questions can only be answered with extensive stability studies.

MPMN: How can these issues be overcome or avoided?

Reilly: Work such as this requires true product development, wherein formulations are built, tested, evaluated, modified, built again, etc. To achieve the four goals previously identified, it is often critical to be able to make adjustments to the silicone formulation itself. For example, in the course of our work with drug-delivery product development, NuSil chemists frequently make adjustments to the types and levels of reinforcing media, the types of polymers, and the reactivity thereof. This iterative system of formulation and manufacture requires expertise with silicone chemistry and processes. It also relies heavily upon the ability to quickly and effectively evaluate formulations for processability, mechanical performance, and drug-elution performance. Such evaluation requires a multitude of testing capabilities, including extraction; analytical methods for identity determination and assay; elution testing, intended to model end-use environment and predict performance; and content uniformity testing. Some projects require limited iterations before a successful candidate formulation is achieved, but some require much more--sometimes upwards of 10 iterations. This is why it is critical that a company undertaking this work has or obtains the capacity for quick formulation development and analysis.

Innovative Medical Device for Developing Countries Hangs on by a Thread

Acting as a microfluidic channel, a simple piece of cotton thread is at the core of a novel diagnostic device developed by a team of students at Johns Hopkins University. Dubbed FeverPoint, the easy-to-use, lightweight, mobile self-test is designed to diagnose the underlying cause of a fever--such as malaria, bacterial pneumonia, or another infection--in developing countries.

"The future of medical device innovation is taking ordinary things and creating something lifesaving," says Omid Akhavan, a graduate student in the Department of Biomedical Engineering. "There had been some research done on thread as a microfluidic channel, and we found a way to take it to the next level."

To produce a diagnosis, the device simply requires the patient to prick his or her finger to provide a small blood sample, much like with an insulin test. The thread, according to the students, features natural microfluidic properties that move the blood sample along its length, exposing it to targeted biomarkers. As a result, the test yields information in five minutes on whether an infection is, in fact, present and if it is viral, bacterial, or malarial in nature.

Although similar tests do exist, many of them require plasma separation from blood prior to testing while others employ expensive and bulkier technology, according to the students. FeverPoint, in contrast, accepts a whole-blood sample and has a cost estimated at three cents per test.

Because it is low cost, portable, and does not require electricity, water, or sample preparation, the Johns Hopkins device holds promise for use in developing countries. In such areas, healthcare workers often do not have access to devices and equipment with which they can accurately and quickly diagnose the cause of a life-threatening fever and treat accordingly. For example, more than three-million children under the age of five die each year from malaria and bacterial pneumonia, according to the World Health Organization; many of these deaths could have been prevented with the proper tools. The students hope that their diagnostic device could help to curb this problem and save lives.