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Novel Metal Casting Process Could Benefit Medical Device Manufacturing

Molds made using maskless photopolymerization technology and airfoil components produced using this technique could be applied to manufacturing medical device parts. (Georgia Tech photo by Gary Meek)

Developed by researchers at the Georgia Institute of Technology (Georgia Tech; Atlanta), an all-digital method for casting metal components that allows manufacturers to make parts directly from computer-aided design (CAD) could change manufacturing practices, including in the medical device industry. The new method speeds prototype development times and improves the efficiency and cost-effectiveness of manufacturing procedures after a part moves to mass production.

Developed by Suman Das, a professor in the George W. Woodruff School of Mechanical Engineering, the new approach relies on a technique known as investment casting, or lost-wax casting. Dating back thousands of years, this process is performed by pouring molten metal into an expendable ceramic mold to form a part. The mold itself is made by creating a wax replica of the part to be cast, surrounding or 'investing' the replica with a ceramic slurry and then drying the slurry and hardening it to form the mold. The wax is then melted out--or lost--to form a mold cavity into which metal can be poured and solidified to produce the casting.

While Das's efforts are focused on manufacturing turbine-engine airfoils for the aeronautics industry, investment casting is also used in a range of other industries, including medical device manufacturing. Most precision metal castings today are designed on computers, using computer-aided design software, Das remarks. However, the next step--creating the ceramic mold--involves a sequence of six major operations requiring expensive precision-machined dies and hundreds of tooling pieces.

In contrast, the new method involves a device that builds ceramic molds directly from a CAD design. Called large-area maskless photopolymerization (LAMP), this high-resolution digital process accretes the mold layer by layer by projecting bitmaps of ultraviolet light onto a mixture of photosensitive resin and ceramic particles. It then selectively cures the mixture to form a solid. 

The technique places one 100-µm layer on top of another until the mold is complete. After the mold is formed, the cured resin is removed through binder burnout, and the remaining ceramic is sintered in a furnace. The result is a fully ceramic structure into which molten metal, including nickel-based superalloys and titanium-based alloys, are poured. "The LAMP process lowers the time required to turn a CAD design into a test-worthy part from a year to about a week," Das notes. "We eliminate the scrap and the tooling, and each digitally manufactured mold is identical to the others."

The new process not only creates testable prototypes but could also be used in the actual manufacturing process, Das states. That would allow more-rapid production of complex metal parts in both low and high volumes and at lower costs in a variety of industries. "When you can produce desired volumes in a short period without tooling," he adds, "you have gone beyond rapid prototyping to true rapid manufacturing."

Microfibers Extrusion: The Foundation for Biotextiles

Microfibers Extrusion: The Foundation for Biotextiles

Medical microfibers and yarns are the critical building blocks of biotextiles. These specialized fibers are intricately knitted, woven, or braided into the biotextile components that are used in many of the implantable medical devices available today. The first medical fibers were developed decades ago for sutures, with fiber technology evolving to enable the biotextiles comprising the first cardiovascular grafts nearly five years ago.1 As fiber technology and the fabrication capabilities of these materials continues to be realized, new applications for the next generation of implantable medical devices, surgical fabrics, wound care, and tissue engineering applications are possible.

The medical-grade fibers and yarns used for implantable medical devices are produced through three primary techniques based on the extrusion of a polymer melt or solution:2
 
  • Melt Spinning. A polymer is heated to its melting point and is extruded through a spinneret to form continuous fiber strands.
  • Dry Spinning. Similar to melt spinning, however, the process starts with a polymer being dissolved in a volatile organic solvent to form a polymer solution. The solvent is later removed during a heated drying stage.
  • Wet Spinning. A polymer is dissolved in a suitable nonvolatile solvent and strands pass through a coagulation bath following extrusion from the spinneret to remove any solvent.
 
The economic, production, and scalability benefits of the melt-spinning process, without the use of solvents, has made this the preferred technique for medical fiber production today. Conventional melt-spin techniques are capable of producing fibers of single-polymer chemistry at high speeds and volumes. As melt-spin technology continues to evolve, resulting in enhanced fiber capabilities to include multipolymer systems for bicomponent or multicomponent fibers, the technology has become a commercially viable option. Dry spinning and wet spinning techniques can potentially be used to produce strands with multiple components, however work in this area remains in the research stages.
 
The next generation of implantable, textile-based medical devices requires the latest technologies for addressing the uniqueness of each application’s specific performance needs. When selecting a fiber supplier, medical textile manufacturers should consider partners who take a collaborative approach to product development to ensure project success. Another important consideration is to select a partner with a keen knowledge of polymer chemistry with the capability to fully characterize a polymer prior to extrusion. Fully characterizing the chemical composition and physical properties of the resulting fiber ensures the absence of polymer degradation byproducts. A well-aligned partner will also have an understanding of the medical device industry and the regulatory path, and will manufacture in a certified Class 10,000 cleanroom with compliant materials and validated processes. An aligned fiber partner will offer the most material knowledge while assuring their manufacturing process and related test methods remain validated and operate in a state-of-control.
 
One company that is focused on improving medical microfiber technology employs a unique melt-spin process known as ARmicron high-definition microextrusion (HDME). This technique uses nano- and micron-sized fibril components to form precise, unique structures within a fiber. The level of detail and definition using the HDME process enables intricate polymer domains within a fiber. This article focuses on the custom fiber and yarn manufacturing capabilities of the ARmicron HDME melt-spin process, which has application in a variety of implantable medical devices.

Fiber Customization

Nonresorbable Resorbable
Polyethylene
Polypropylene
  Polyethylene Terephtalate (PET)    Polyurethane (PU)
Polymethyl Methacrylate (PMMA)
Polyetheretherketone(PEEK)
Polylactic Acid (PLA)
Polyglycolic Acid (PGA)
Polylactide/Glycolide Copolymers (PLGA)
Polycaprolactone (PCL)
Table I. Examples of biocompatible polymers.
Traditionally plastics and metals have been used as base materials for a wide variety of medical devices. However, biocompatible nonresorbable and resorbable fiber polymer choices are offering textile fabricators a wider range of material options for creating innovative, less invasive product constructions for a wide range of implantable medical devices (see Table I).
 
Creative use of these materials allows fiber manufacturers to produce fibers within fibers to take advantage of resorbable and nonresorbable properties simultaneously. The HDME process makes it possible to use up to four polymers during the manufacturing process to produce a wide variety of customized fibers. Another unique capability of the HDME process is the production of spun fibers with diameters of 300 nm using an islands-in-the-sea technique coupled with dissolvable and nondissolvable materials.3 This technique also enables the use of a small number of strong permanent fibers coupled with dissolvable fiber material to produce a lower profile final fabric.
 
The trend for small, minimally invasive devices intended for quick insertion and removal has a direct effect on the desired characteristics of a fiber. Fibers incorporated into the fabric portion of an implantable device must enhance the product’s conformability, be compressible, and be able to expand to offer flexibility and functionality in the finished device without restricting movement within the body.4 This demand is fueling a growing need for thinner and finer diameter fibers while maintaining tenacity. The HDME melt-spin process produces a unique islands-in-the-sea sheath-core fiber architecture as one way of addressing these needs.
 
In addition to the nondissolvable and dissolvable core-sheath fibers possible with the islands-in-the-sea approach, HDME provides the capability to produce hybrid fibers comprised of component fibers designed with different performance functionalities. For example, the inner fiber can offer the required strength needed, while the outer fibers possesses other properties such as a desired aesthetic, low melting properties for better bonding, inertness within the body to reduce inflammation, or barrier properties to provide a fluid barrier. The following section discusses the unique fiber capabilities of the HDME process in further detail.
Medical microfibers are knitted, woven, or braided as a critical component to form many medical implants.

Fiber Characterization

All fiber manufacturers control the chemistry as well as the fiber’s physical properties, including denier, tenacity, elongation, and shrinkage to meet the specific performance requirements of an application. Producers of medical fibers require additional control to ensure potential polymer changes are minimized and well understood throughout the fiber manufacturing process via polymer characterization. Such controls include using physical, chemical, and analytical techniques on an ongoing basis. Various optical techniques such as scanning electron microscope are also useful for the determination of fiber uniformity, surface roughness, and identification of defects during the fiber development process. The optical techniques can also be implemented as tools for use after fiber development is complete if so desired.

Fiber Architecture

Conventional melt-spin processes typically produce fibers based on one polymer type, while fibers produced from the HDME process can be developed by coextruding multiple polymers to create specific polymer domains within the fiber. The process enables customized fiber constructions including monofilament, multifilament, and low denier per filament (DPF) yarns from a wide range of select biocompatible nonresorbable or bioresorbable polymers. Also unique to this process is the ability to create one-of-a-kind fiber architectures unachievable through other techniques. The HDME process leverages multicomponent extrusion capabilities to create desired fiber cross-section designs for increased functionality.
 
The HDME process can produce fibers that incorporate up to four differing polymers to build transition gradients.
Using this approach, a fiber can feature up to four differing polymers of varying architectures including noncircular, noncentric, transition gradient, and sheath-core architectures. Hybrid fibers can be created using these techniques and by combining resorbable and nonresorbable fibers. The islands-in-the-sea image features multicomponent fibers with highly resolved internal domains using a modified sheath-core architecture approach for a surgical fabric to provide strength and support for cell growth. Over time, portions of the fibers will dissolve making the fabric less invasive while offering continued strength with the remaining inner nonresorbable fibers.
 
Fibers can also be developed with external submicron surface architectural definitions that may be beneficial for directional cellular ingrowth. The regeneration of some tissues, such as tendons, ligaments, nerves and muscles require cell alignment on one or more axes to optimize their functions.5 As seen in the fractal fibers image, the HDME process is capable of creating a continuous non-Euclidian external lateral fractal surface architecture simultaneous with internal spatially and gradiently resolved fiber domains for custom scaffold and fiber designs.
The HDME process enables the use of multiple polymers to produce a fiber’s internal structure combined with a protective sheath, while providing the desirable physical properties conducive for textile manufacturing. Because the typical weaving and braiding manufacturing processing can potentially cause the collapse of a fiber’s nanometer surface structures, the protective sheath preserves the internal architecture during the textile process and can be removed at a designated time during the process to maintain the fiber’s architectural integrity.

Applications for Today and the Future

Medical fibers have historically been used within the fabric components of implantable medical devices such as surgical fabrics, sutures, stents, and grafts for short- or long-term use. HDME technology is a custom product design alternative to traditional filament-fiber science. This process offers precise control of both external architectures and internal matrix morphologies for specialized and model applications to medical fibers with potential use in implants, medical textiles, and wound healing products.
 
An illustration of a fractal fiber core shows the aligned channels of the fractal surface, which creates grooves to enable cell alignment and topographical control of cell orientation.
As it relates to tissue engineering, 3-D micro-nanofabrication of the HDME fiber design helps transition tissue scaffold designs away from traditional Euclidian geometries to specialized   fractal designs. HDME precisely and simultaneously produces both external non-Euclidean (i.e., lateral fractal nanopattern) and internal gradient transition cross-section, which can support the assembly and “trophic-doping” for improved scaffold features.
 
Product developers may opt to load custom-designed gradient microfiber architectures for specialized tissue engineering, scaffold design, or wound healing with cross-section transition domains that promote controlled release, spatially resolved growth agent incorporation, and managed multicomponent biopolymer matrix biodegradation. A future capability of the technology may offer product developers the option to combine controlled release with custom architecture.

Conclusion

The development of the next generation of medical devices will be fueled by advancements in component materials to deliver the enabling technologies to turn product concepts into realities. New fiber material options and capabilities available through high-definition microextrusion melt-spin technology create customized fiber constructions including monofilament, multifilament, and DPF yarns select biocompatible nonresorbable or bioresorbable polymers to create unique and enabling fiber architectures. The use of HDME techniques coupled with collaborative custom fiber development, clean manufacturing, polymer/product characterization, and ingenuity can make new applications in medical implants, wound care, and drug delivery devices a reality.

References

1. JM Koslosky, “Biomedical Textiles Stay in Step with the Beat of Cardiovascular Designs.” Medical Design Technology (2011).
2. K Tuzlakoglu, L Reis, “Biodegradable Polymeric Fiber Structures in Tissue Engineering.” Tissue Engineering: Part B 15 (2009): 17-27.
3. Hills Inc., “Production of Sub-micron Fibers in Non-Woven Fabrics,” Barrier Fabrics of Spunbound Specialty Fibers for Medical Applications (West Melbourne, FL, 2012).
4. Secant Medical, “What are Biomedical Textiles?” (April 2012).
5. Q Lu, A Simionescu, and N Vyavahare, “Novel Capillary Channel Scaffolds for Guided Tissue Engineering,” Actabio Materialia (2005): 607-614.
 
Greg Toney is manufacturing manager for medical fibers at Adhesives Research Inc. (Glen Rock, PA). He focuses on the organization and production processes for permanent and biosorbable fiber structures. He holds a BS in chemistry from Wofford College and a MS in chemistry from Furman University. He has 36 years experience in material science, polymer processing, and engineering in extrusion, coating, textil,e and nonwoven processing, and polymer additives. Reach him at [email protected]
  Ming Wei, PhD, is product development chemist at Adhesives Research. Prior to joining the firm she was a research professor in the plastics engineering department at university of Massachusetts Lowell (UML). She obtained her doctorate degree in plastics engineering from UML and has been working in the field of polymer science and engineering since 1996. Reach Wei at [email protected]
  Bob Wigdorski is senior research & development scientist at Adhesives Research. He is responsible for the development of adhesive technologies for industrial and electronics markets, and provides technical support for the covert marker authentication technologies and medical fibers portion of the firm’s product portfolio. He has 42 years experience in the adhesives and coatings industry and graduated from the the State University of New York at Buffalo. Contact him at [email protected]
 
 

Women in Medtech: Kathryn Stecco, Pushing the Cutting Edge of Medicine

Kathryn Stecco, MD is a medical device executive, entrepreneur, and a surgeon who is the co-founder and chief medical officer of Altai Medical Technologies (San Jose, CA), which specializes in mobile health, medical device, biotech and health information technologies. At Altai Medical Technologies, Stecco leads medical research, guides in vitro and in vivo pre-clinical research, and develops domestic and international clinical and regulatory strategies.

She also works as a medical consultant EndoShape Inc. (Boulder, CO) and Allurion Technologies Inc. (Wellesley, MA). In addition, Stecco serves as the medical director of Nfocus Neuromedical Inc. (Palo Alto, CA). She also has a concierge medical practice and operates a sole proprietorship that specializes in due diligence on emerging medical technologies for venture capital firms, medical device companies, and biotechnology companies.

Stecco has been mentored by the likes of medical device innovators Mir Imran, Thomas Fogarty, MD, and Michael Laufer, MD. She earned her MD at the University of Southern California and completed her residency in general surgery at Stanford University. 

MD+DI: How did you get started working in the medtech industry?

Kathryn Stecco, MD: I began conducting clinical trial research in graduate school at the University of Southern California. This early experience extended to clinical outcomes research during medical school. During my general surgery residency at Stanford University, I was able to work with three medtech gurus: Tom Fogarty, MD, Michael Laufer, MD, and Mir Imran. All three significantly influenced my career.

I was an intern for Dr. Fogarty when I rotated through vascular surgery. I performed pre-clinical research with him and his engineers on several of his device companies. Dr. Laufer and I spent a lot of time on trauma call discussing new procedural innovations. Later in my career, I conducted several clinical trials and co-founded a couple of device companies with him. During my research years, I was the medical director for Mir Imran at his device incubator.

Tom Krummel, the Stanford Department of Surgery chair, was progressive and supported the pursuit of medical technologies. Surgery residency is brutal and we were still doing every third night of in-hospital call, but I loved it because the experience was so unique. To this day, I work closely with many of my Stanford colleagues. 

MD+DI: What are the main challenges you see working in medtech?

"It is important to be realistic about the medical outcomes and their utility. If a technology works, the data will speak for itself."

Stecco: Dealing with human biology is more complex and highly regulated compared to developing a social networking website for example. It is critical to design the pre-clinical and clinical research to render the most efficient answers to make the technology successful. You cannot turn an idea into a research project. New technologies carry a lot of hype because there is money involved. However, it is important to be realistic about the medical outcomes and their utility. If a technology works, the data will speak for itself.

MD+DI: What advice would you give to people looking to get into this field?

Stecco: First and foremost, have a great respect for patients and improving their overall quality of life, especially when developing implantable and life-saving devices. There is a lot of monetary pressure but patient safety and personal integrity should never be compromised.

Second, embrace paradigm shifts in healthcare. Medical practice and reimbursement have radically changed. The health insurance debacle has led to the growth of the concierge medical practice and a focus on preventive medicine. In the future, we can expect more tailored medical care with the development of personalized genomics. In addition, the rapid growth of social media and digital technologies empowers both physicians and patients with mobile health and telemedicine applications. Some of the simplest devices are the most effective.

MD+DI: Are there barriers to women entering medtech? How can they be overcome?

Stecco: The majority of investors, engineers, CEOs, and CMOs are male so it just depends on the type of culture they foster within each organization. Women need to be experts in their disciplines, have thick skin, and not be easily intimidated. It also helps to have a great jump shot.

MD+DI: How can we get more women involved in this field?

Stecco: Strong successful women should take pride in being a mentor to other women entering the medtech industry. In addition to being supportive of each other, networking and using social media to educate people about the field is important.

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

Using FEA Analysis and Fatigue Testing to Optimize Patient-Specific Total Knee Systems

An example of a six-cut x-small model.
An example of a five-cut small model.
Total knee replacement has become a common major surgical procedure with more than 600,000 cases being performed annually in the United States. Twenty years ago, most patients who underwent total knee replacement were more than 68 years old; today’s average patient age is 62. As the patient population gets younger, their more active lifestyle will put additional demands on the implant systems they require. These additional demands, along with longer life expectancies, means that many patients who receive total knee replacements will require a revision later in life. There are two prevailing philosophies regarding designing devices for knee replacement revisions. One philosophy dictates to design the implant system to last as long as possible with no regard for how it will be revised in the event that a revision is required. The second and more broadly held philosophy is to design an implant with the next surgery in mind.  

Method

ConformMIS set out to design a patient-specific knee femoral component that was bone preserving in comparison to standard total knee components. Designing a total knee replacement that will fit a patient’s geometry requires detailed information that can only be provided by a CT scan. The CT data is postprocessed and converted into a CAD solid model using proprietary software. A secondary proprietary software system is then used to analyze the bone geometry and design the femoral component. User-defined attributes are applied in the design process as well as predefined design rules that are embedded into the software. The predefined design rules include the coronal radii for the trochlear groove and condyles, which are designed with low polyethylene wear in mind, employing radii that have been shown to produce low contact stress. The embedded design rules include recreation of the patient’s natural sagittal ‘J’ curves for the medial condyle, the trochlear groove, and the lateral condyle.
 
A bone-preserving implant design requires thinner cross-sections of the femoral component and less bone removal in the implantation procedure. Fracture of the femoral component is not a common failure mode in total knee replacement, but fatigue strength can be compromised when attempting to make condylar sections thinner than standard total knee components. Traditional total knee replacement femoral components employ a multifaceted bone side geometry. ConforMIS hypothesized that adding an additional facet would reduce the thickness of the femoral component.
 
One study investigator reported on seven knee femoral fractures in his early press-fit-condylar (PFC) experience.1 Failure analysis of these components revealed that the fracture initiation site was on the inner bone surface at the intersection of the distal flat and posterior medial chamfer corner. This finding indicates that in these cases, femoral fracture was caused by the femoral component spreading apart in the anterior to posterior direction, concentrating peak stress at the medial distal and posterior chamfer intersections.
 
Using the knowledge of how the early PFC knee femoral components failed, ConforMIS and Farm Design set out to simulate the failure mechanism in a FEA model. Two implant sizes were analyzed: an extra small femoral component and an extra large femoral component. The intent was to develop a comparative study that examined the expanding forces of the femur, provided flexibility for multiple design iterations, and was capable of being fatigue tested in the laboratory.
 
Models of the implant and femur assembly were created in a worst case scenario with the condyle load pads oriented to mimic heal strike combined with a slight interference fit from the femur. Loads were applied to the condyle pads in a vertical direction parallel to the femoral axis while the top of the femur was fully fixed. The magnitudes of force were derived from actual patient weight data correlated to knee implant size. The loading distribution was based on biomechanical analysis conducted by another researcher with 60% of the load applied to the medial condyle and 40% of the load applied to the lateral condyle.2 Using this setup as the baseline (with and without a femur interference fit), the chamfer angles and number of cuts were modified for small and large implants.
 
The load inputs were broken up into two steps for the interference fit FEA models. Time step-one looked at the stress results with no load on the condyle pads but with the interference fit applied. Time step-two looked at the interference fit plus the medial and lateral condyle loads. For the line-to-line model, there was only one time-step for the condyle load inputs. Maximum principal stresses and deflections were monitored for each setup and evaluated across design iterations.

Results

The results for the maximum principal stress were tabulated and in all femoral components. The maximum principal stress occurred at the intersection of the distal medial and posterior chamfer intersection. In our FEA model, the five-cut design increased the maximum principal stress on the femoral component by 24% in the XS size and by 32% in the XL size as compared to a six-cut design.

Fatigue Testing

 The FEA study showed that maximum principal stresses can occur at the intersection of the distal and posterior facets on the medial side of a femoral component. This result is highly consistent with the implant failure results reported by the first study in the article. Fatigue testing was conducted on the six-cut implant designs described in the FEA study. Femoral components were manufactured from cast cobalt-chrome alloy conforming to ASTM F-75 and then ground and polished to finished specifications. Special attention was paid to insuring that the thickness values of the component were at the low end of the acceptable tolerance range, thereby creating a worst case condition for strength. Each femoral component was measured for the anterior to posterior dimension on the bone cut side of the implant. This consistency was required to fabricate a holding block that would produce the prescribed interference fit that would cause the wedging affect to spread it apart in the anterior to posterior direction. Individual holding blocks were then printed in the selective laser sintering process in glass-filed nylon. The engineered interference fit for each femoral component was 0.5 mm at the proximal tip of the trochlear flange. The femoral components were cemented onto the holding blocks using polymethylmethacrylate (PMMA) bone cement. Loads were applied to the femoral component with 60% of the force passing through the medial condyle with the remaining load passing through the lateral condyle. A polyethylene liner approximately 8 mm thick, simulating a tibial insert, was placed between the femoral component and the load cell. The total load applied varied depending on what size femoral implant was being tested.
 
The implants and fixtures were loaded onto test frames that conform to ASTM E466. Cyclic loading was performed at 10 Hz and was run to 10 million cycles for each of five samples for each size. Each implant, a total of 15 samples, was inspected with standard metallographic methods to detect fractures at the conclusion of the 10 million cycle test. No fatigue cracks were observed in the dye penetrant inspection technique.

Conclusion

The FEA method that ConforMIS developed accurately reproduces the reported failure mechanism of an implant system with a long clinical history. In the company’s model, it demonstrated the exact location of failure of the PFC femoral components.1 Both sized implants showed maximum principal stress in the identical region as the failed PFC femoral components. Although the stress predicted in the company’s model is below any reported endurance limit for a cast cobalt-chrome implant, differences in actual implant thickness and/or magnitudes of the load applied could certainly raise the maximum principal stress above the endurance limit of the material. The company also showed that stress can be reduced substantially by adding an additional faceted cut, going from the traditional five cuts to the new six-cut configuration. We hypothesize that the stress reduction in the six-cut design is due to the additional corner imparted by the sixth facet, distributing the load over a greater area. The advantage of the additional cut is that the overall implant thickness can be reduced by approximately 2 mm compared to the traditional five-cut implant design.
 
Another researcher showed the endurance limit of cobalt chrome as derived from a rotating beam test to be between 345 mPa and 480 mPa.3 This thickness reduction can be achieved because the six-cut design shows a maximum principal stress substantially lower than the endurance limit for cast cobalt chrome as reported in the study. Any reduction in implant thickness can translate directly to bone preservation in total knee surgery, leaving more bone available in the event that a revision of the original implant is required. This six-cut configuration is the basis of the iTotal patient-specific tricompartmental knee replacement system, which enables a personalized femoral component that is thinner than traditional total knee replacements. A thinner implant preserves more bone, which may be beneficial for future treatment options.
 
References
1. RD Scott, Total Knee Arthroplasty (Elsevier, 2006) 117.
2. RE Daley, “Measurement of the Distribution of Forces at the Human Knee Joint,” Ohio State University, PhD Thesis (1975): 75-19, 426.
3. RM Berlin, LJ Gustavson, and KK Wang, “The Influence of Post Processing on the Mechanical Properties of Investment Cast and Wrought Co-Cr-Mo Alloy,” Cobalt-Base Alloys for Biomedical Applications, ASTM STP 1365; JA Disegi, RL Kennedy, and R Pillier (American Society for Testing and Materials, West Conshohocken, PA) 1999.
 
John Slamin is senior vice president of knee implant engineering at ConforMIS Inc. He oversees all product engineering and development for the company’s line of knee implants. Prior to joining ConforMIS, Slamin spent more than 30 years in R&D at Johnson & Johnson's Orthopaedic Division, now DePuy. He was responsible for the product development activities that led to the PFC Total Knee System in 1986 and the Sigma Total Knee System in 1996. He coordinated the design and development of the world's first fully integrated and implantable electronic knee in collaboration with Clifford W. Colwell, MD of SCORE (LaJolla CA) and is the recipient of the Johnson Medal for outstanding Research and Development achievements. Mr. Slamin is the holder of seven patents related to knee implant engineering. He is a graduate of Wentworth Institute of Technology (Boston).
 

Learn more about the design, development, manufacture, and testing of knee implants at the upcoming Orthotec orthopedic conference and expo in Warsaw, Indiana.

 

Navigating Name Changes and Reregistration

Consider these common scenarios: an acquisition or carve-out occurs, and a medical device has a new manufacturer, or a manufacturer decides to change its name as a result of restructuring. Both occurrences are common in today’s rapidly changing business environment. After the dust settles on a name change, it’s often up to company executives to complete the implementation plan and move the new business forward, often with little time or often with fewer resources. However, a manufacturer change or product name change requires modifications to the product labeling and regulatory reregistrations, which are increasingly complex. This article covers key steps required for successful reregistration and labeling changes while presenting strategies to avoid common pitfalls.

Name Change Requirements

Most developed countries require a device to be registered, clearly displaying the legal manufacturer’s name. Abroad, outside the European Union (EU) and United States, about 40% of countries require a CE certificate to register the product. Roughly 20% of these countries require a certificate to foreign government (CFG) or certificate of free sale from the country of manufacture in order to register the product. In the event of a company name change in the United States, FDA requires an update to the registration per 21 CFR 807.26 and 21 CFR 807.30. In the event of a name change for devices sold in the EU, an updated CE certificate is required. All countries that have regulations concerning the marketing of medical devices require some sort of notification in the event of a company name change, which can range from a simple notification to a full reregistration.

Product Labeling

A changed company name also triggers the need to update the product labeling. In the United States, FDA requires registration within 30 days of commercial distribution of the device per 21 CFR 807. FDA 21 CFR 801 requires the name of the manufacturer to be conspicuously displayed on the product labeling. For product sold in the EU, the label must bear the name or trade name and address of the manufacturer per MDD 93/42/EEC Annex 1, 13.3. This requirement applies to all countries that have regulations concerning medical devices.
 
Product labeling is a broad category covering areas including the actual product label, instructions for use, product inserts, packaging, and collateral such as brochures, catalogs, and other promotional vehicles.
 
FDA does not require updated labeling to be submitted in order to change the company name, but clearly expects that the company will be making a good faith effort to update the label copy in a timely manner.

Requirements Beyond U.S. Borders

For products sold to international markets, the requirements for each country must be researched and understood. In order to export the product, correct labeling and FDA registration is needed to obtain Certificates to Foreign Government (CFG).
 
While no blanket rules apply to requirements for all export countries, all countries require the label to match what is listed in the registration. For example, in the EU, the manufacturer information on the label must match the manufacturer information listed on the CE certificate and the Declaration of Conformity.
 
Outside of the EU, it’s not uncommon for CE and ISO certificates to be required as supporting documentation for registration. Each country has its own requirements, so it’s necessary to develop an individualized approach to gathering requirements and developing an implementation plan (see Table I).
 
 

Risks and Pitfalls: Revenue Delays

During the merger or acquisition process, the deal makers might not fully appreciate the reregistration workload or timeframe. This task typically falls upon technical executives after the deal is signed. All too often, the acquiring firm has limited technical staff and a narrow bandwidth to take on such extensive research let alone the implementation in every country, and this often results in revenue delays. The technical executives must deliver the message about these delays to the management team, who made the deal expecting they were buying an established revenue stream from the legacy product.
 
One remedy for delayed revenues is to outsource the product reregistration process. Compliance consultants typically know the county-by-country requirements, which can help to eliminate the delays (see the sidebar “Potential Revenue Delays in Canada and Brazil”). Ideally, the compliance consultants would be brought into the acquisition process during the due diligence stage. This introduction helps the acquiring firm anticipate revenue delays, quantify the reregistration costs, and identify any gaps in testing or technical data, which can be factored into the deal price and/or the posttransition agreements. For example, the postdeal transition agreement might require the seller to continue manufacturing the product until the buyer can reregister the product.
 
 

Crossfunctional Complexities Behind Reregistrations

The reasons that drive product reregistrations are oftentimes fraught with crossfunctional complexity. So while the technical team is reregistering the product and introducing new labeling into multiple manufacturing plants, they’re also responsible for complex tasks resulting from the acquisition. This process could include transferring production, which will trigger reregistration in most countries, managing inventory across multiple country locations, and coordinating product with multiple distributors in various countries. It all takes place while the technical executives must remain focused on their primary job functions such as getting product out the door for sale to customers.

Manufacturing Transfer

Oftentimes the manufacturing location changes as part of the merger or acquisition. Acquiring firms may see value in aggregating plants or in transferring production. The resulting changes in manufacturing location must be included in the registration process.
 
The added registration complexities of changing location fall upon the shoulders of technical executives who have full plates with shutting down the old facilities while bringing new facilities onboard. In addition, they have the challenge of introducing new labeling into the manufacturing process, and a change in location can be a trigger for facility inspections in many countries.

Distribution Challenges

Introduction of new product and obsolescence of the old product requires coordination across manufacturing and distribution sites for each country. For countries with a long reregistration process, it means old product needs to be reserved. Other countries, such as Spain, will allow a mixture of old and new product to be imported but will fine the company for sending the old product after they start receiving the new product. For some manufacturers with multiple distributors in each export country, the coordination is very complex and falls upon technical personnel already engaged in other aspects of the merger or acquisition.
 
Some countries allow for a transfer of registration between distributors with a short approval time, however other countries require new or reregistration when a distributor is changed as the distributor or in country representative is the owner of the registration.

Planning is Everything

A clearly laid-out plan that coordinates the registration with the labeling revision process and any potential manufacturing site changes is essential to ensure continued market access and channel inventory for the product. The plan provides visibility for introducing the newly labeled product into the various U.S. and export markets.

Conclusion

Changes to the company name require modifications to the labeling and reregistration of the product in every country of distribution. It requires a well-researched project plan that addresses the requirements of each country and coordinates crossfunctional activities across the company. Given the complexity of determining and implementing the plan, experts recommend that companies determine the costs and potential revenue delays before embarking upon a name change. In the case of mergers or acquisitions, it’s important that technical executives are part of the due diligence team so these costs and revenue delays can be factored into the deal price. When the technical executives are stretched thin between doing their day jobs and handling the reregistration, expert consultants can help quantify these costs and delays and are available to help implement the plan after the deal closes.
 
Chris Henza is a regulatory affairs specialist with Regulatory Compliance Associates Inc. Henza has been the interface with regulatory authorities for small and large companies on domestic and international product registration, production changes, design changes, and documentation remediation. Henza also wrote "Reforming the 510(k) Process: Where We Are, How We Got Here, and What's to Come". She graduated from Northeastern Illinois University with a BS in Biology and can be reached at [email protected]
Nicohl Wilding is a senior auditor and regulatory SME for Regulatory Compliance Associates. Wilding has more than 14 years’ experience in the medical device and pharmaceutical industry incorporating all aspects of drug and device development including clinical research, data management, regulatory affairs, and quality system implementation and management. She has written and managed numerous submissions to U.S. and international regulatory agencies, and developed global regulatory strategies for medical devices. She graduated with a BS degree from the University of Illinois, Chicago and can be reached at [email protected]
Portions of this article are copyrighted by Regulatory Compliance Associates Inc. and have been printed with permission.
 


 

House Subcommittee Hears Testimony on Downsides of Healthcare Consolidation

In testimony given today before the House Subcommittee on Intellectual property, Competition, and the Internet, a representative for a conservative think tank drew attention to the trend toward consolidation in healthcare, which could spell bad news for the medical device makers.

Scott Gottlieb, a resident with the American Enterprise Institute, cited an Accenture Health report that predicts a 5% annual decline in the number of independent physicians beginning in 2013. Meanwhile, 70% of national hospital and health systems plan to hire more physicians over the next three years.

Salaried physicians, he said, use fewer diagnostic tests and procedures than their counterparts in private practice. Though that results in lower costs, Gottlieb, a former FDA deputy commissioner, said that the phenomenon could be a symptom of lower productivity among salaried physicians.

He also argued that the uptick in healthcare consolidation is no coincidence.

“[The Patient Protection and Affordable Care Act] contains deliberate constructs to industrialize healthcare by moving physicians onto capitated arrangements and larger groups where reimbursement, utilization, and quality measures can be more tightly controlled,” he told the subcommittee.

Jamie Hartford
 

Weekly Vitals: Recalls Soar in Q1, Breast Implant Scandal Plot Thickens, and More

Medical device recalls are on the rise, the Stericycle ExpertRECALL announced this week. The recall tracking group stated that recalls increased more than 160% in Q1 of 2012, which affected more than five times as many units as in the previous quarter. And speaking of recalls, the plot thickens in the case of the PIP breast implants as it was revealed this week that surgeons had notified the Medicines and Healthcare products Regulatory Agency as far back as 2006 with concerns regarding the faulty products. Read about these and more of the week's top stories in our roundup below.
 

What a Difference One E-Mail Made in the Device Tax Fight

No 2.3%This week, CareFusion CEO Kieran Gallahue lent his support to the grassroots no2point3.com medical device petition.

Gallahue, an AdvaMed board chairman, sent an email to U.S.-based CareFusion employees to consider signing the online petition which launched on April 17, 2012. Nearly a quarter of those contacted responded, putting CareFusion atop the site's "Corporate Leaderboard," and ahead of fellow California-based companies NuVasive (with, at present, more than 700 signatures) and Volcano Corporation (nearly 400 signatures).

No2point3 founder Joe Hage puts Gallahue's effort in perspective. "750 petitioners signed the day I launched the site to the 100,000-member Medical Devices Group. Kieran's one email to his employees generated more signatures in one day than I could with 15 times the reach!"

At present, 67 companies, each collecting five or more employee signatures, are represented on the no2point3 leaderboard.

"Where are the other 333 companies represented on the July 18, 2011 letter to Congress to repeal the effort?" Hage asks. "Imagine if each of the 400 companies rallied their employees to sign the petition. It's their employees that will be hit hardest. We need them to stand in unison against the tax."

"We need more 'Kierans,' more CEOs ready to put their employees behind the effort, if we're going to succeed," added Hage. "It's as simple as that."

At the time of writing, the no2point3.com petition has collected more than 6,000 signatures toward its 25,000-signature goal by July 18, 2012.

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

The MX Q&A: Richard Hassett, NovaSom

If a physician’s goal is to alleviate patients’ suffering, then Richard Hassett has his dream job. A neurologist by background, Hassett is president and CEO of NovaSom, a manufacturer of home tests for obstructive sleep apnea based in Glenn Burnie, MD. An alternative to sleep lab testing, the device enables patients to assess themselves in the comfort of their homes at a fraction of the cost of in-center tests, Hassett says. If NovaSom’s extended overnight testing delivers a positive diagnosis, then the patient can get treatment and eventually get to sleep restfully, perchance to dream through the night.

"Finding these patients and treating them produces real health benefits for individuals and real savings, and that’s very motivating to me." —Rick Hassett

NovaSom appeals to the physician in Hassett. “What got me excited about NovaSom, frankly, was the fact that first of all there’s this undiagnosed public health epidemic that is coming into focus, and it’s big,” he says. “Finding these patients and treating them produces real health benefits for individuals and real savings, and that’s very motivating to me.”

Prospects for the 100-employee company have also motivated bullish investors. In June 2011 the company raked in $35 million in equity financing, said to be one of the top 10 VC hauls of the year. NovaSom has also attracted big names. Michael Coppola, president and chief medical officer of the American Sleep Apnea Association joined the company in April 2012 as chief medical officer and vice president of medical affairs. Before Hassett became chief executive, Thomas Fogarty had helped the company, founded as Sleep Solutions in 1992, with the product’s design. Last year NovaSom released a new wireless version of the FDA-cleared device, called the AccuSom.

Hassett says the outlook for home sleep testing “changed dramatically” in the four years since Medicare “published a favorable coverage decision.” United Healthcare will begin authorizing use of the home tests this year. Aetna and other insurers have already endorsed prior authorization or are about to follow suit, Hassett notes.

Hassett began his medical career in solo practice before taking up a full-time academic neurology residency in Philadelphia. He began his transition to business and technology side of healthcare in the late ‘90s. Most recently, he served as president and COO of Matria Healthcare. Hassett also served previously as CEO of Coordinated Care Solutions, CEO of Vivra Asthma & Allergy, and CMO and executive vice president of operations for Accordant Health Services.

Hassett’s discussion with MX encompasses NovaSom’s outreach efforts, the growing recognition of sleep apnea’s spread, lab-versus-home testing, comorbidity questions, a key Waste Management study, and internal discussions about what instructional voice to use for the new device.

MX: NovaSom has received $75 million in equity funds since 2008, and the company’s business strategy has shifted to convincing insurers and employers to support the use of home tests. How smoothly has that gone? I understand that United Healthcare has agreed to pay for the tests for its subscribers.

Richard Hassett: That’s correct. This is a big year for NovaSom. United Healthcare is rolling out prior authorization this year, meaning that they will be inserting themselves into the process in order to determine whether or not a patient for whom sleep apnea is suspected really needs to go to a facility to have the more complicated but also more expensive test or is appropriate to be tested at home with the NovaSom [device]. Similarly, Aetna has installed prior authorization nationwide. Several other regional payers have done the same. By the end of the year we expect that most of the Blues will have done so.

In our minds this use of prior authorization has been helpful in getting the ball rolling. The truth is, most primary care physicians and patients have not heretofore been aware that there was an opportunity to test at home if sleep apnea was suspected. I think the introduction of prior authorization here is critical in terms of driving awareness and driving clinically appropriate utilization of home sleep testing. Not everybody should be tested at home, but many can be. It’s private, it’s comfortable, it’s inexpensive, it’s accurate, it doesn’t require childcare or travel, and you don’t have to live in a big city where there are facilities.

MX: Are there cases where a lab test is preferable, and what determines that?

RH: Definitely. I’m in the business of what’s referred to as “out-of-center” sleep testing, or home sleep testing. I’d be the first to admit that there are many patients for whom a sleep center is exactly where they need to go. To begin with, out of a hundred patients who walk in the front door of a sleep center they are not all there to rule out sleep apnea. There are other sleep conditions, and NovaSom does not test for narcolepsy or nocturnal seizures or movement disorders or anything like that. Out of a hundred people who walk in the front door of a sleep center, maybe 10 or 15 of them are there for other reasons entirely, and we would never test to rule out those conditions.

MX: And those would be the reasons that lab tests are called for?

RH: Sure. And then there are patients who have advanced heart or lung disease, so if someone being tested for sleep apnea has end-stage emphysema, for instance, and is oxygen-dependent, or has advanced heart failure, those patients deserve to be under the watchful eye of the sleep center.

Having said that, the vast majority of patients who are being tested in sleep centers are clinically appropriate for home sleep testing. Frankly, the capacity and the access that is enabled by home sleep testing is exactly what the doctor ordered, if you’ll pardon my pun, because the number of undiagnosed patients with sleep apnea is staggering.
 

MX: The company says that 85% of the 18 million or so who have this condition have yet to be treated for it.

RH: That 18 million refers just to the patients who have moderate to severe sleep apnea. Those are the patients for whom the literature is clear that treatment is required and beneficial.

MX: If they’re undiagnosed how do they know they even have this problem? How do you reach them?

RH: You’ve asked the million-dollar question there, because most of those patients right now think they snore loudly and it’s a bit of a punch line around the dinner table on a Sunday night.

MX: What if you live alone and have no one around to hear you snore?

RH: Snoring is one obvious example. Many patients will also complain of being drowsy during the day, falling asleep at work, falling asleep every time they sit in front of the TV, being inattentive, distracted, showing poor productivity, and having a lot of work-life challenges. These are the kinds of things where you say, “Gee, that makes sense that chronic sleep deprivation would produce those symptoms.” What happens is, every time you get into REM sleep, you’re choking, you’re strangling, and you get aroused from that restful sleep.

Frankly, it’s the primary care physicians of America who need to rise to the occasion here.

MX: How do you connect someone with this problem with the doctor who could diagnose it and suggest a home sleep test?

RH: To be clear, we alone are not doing this, because we’re a small company. There are 40 million sufferers of sleep apnea, if you include mild [cases], and there must be 300,000 primary care physicians. The sleep specialty community, the relevant academies of internal medicine, family [practitioners], even pediatricians, the payers, employers, health and wellness companies [have to be involved]. Frankly, the awareness of sleep apnea is increasing every day. Although this condition is massively underdiagnosed now, I will tell you that 20 years ago it was essentially unheard of. Nobody talked about it; nobody knew about it. Now because I’m in the business I’m in when I tell people about NovaSom they say, “You know, I never heard of this five years ago, but my dad has it, my brother just got tested, and my boss has it.” People are becoming aware of it.
One of the ways that sleep apnea rears its head is through the effect that it has on other health conditions. For instance, [if there is] unexplained high blood pressure or high blood pressure that is refractory or resistant to multiple medications, odds are it’s sleep apnea. New onset of atrial fibrillation, a very common arrhythmia? Good chance it’s sleep apnea.

One of the ways that sleep apnea is resonating with the doctors of America, consumers, health plans, and employers, is because there’s an increasing awareness now of the overlap between diabetes and sleep apnea, high blood pressure, heart failure, heart attacks, strokes, obesity, [and] depression. In fact, with each of those diseases there’s roughly a 50-50 overlap, meaning if you have sleep apnea what’s the chance you have x? And if you have x what’s the chance you have sleep apnea? We’re realizing now that sleep apnea alongside hyperlipidemia and tobacco and diabetes and hypertension is really one of the drivers of this whole ischemic crisis that we have, where strokes and heart attacks are driving so much cost and morbidity and mortality in our healthcare delivery system.

So what got me excited about NovaSom, frankly, was the fact that first of all there’s this undiagnosed public health epidemic that is coming into focus, and it’s big. Finding these patients and treating them produces real health benefits for individuals and real savings, and that’s very motivating to me. Furthermore, there’s an opportunity to make the diagnosis at a fraction of the cost in a way that’s highly accurate and that’s exactly what’s necessary if we’re going to get after this big public health epidemic.

I’m trying to focus on how this 85% know to have this condition checked out and then be directed to your product.
RH: There isn’t any one channel. I wouldn’t say, “Oh, we’re advertising on TV, or we’re advertising in Redbook,” or anything like that. There are lots of commercial and noncommercial interests aligned around driving the awareness campaign among consumers, whether it’s celebrity spokespersons like Shaquille O’Neal getting on his soapbox and talking about his diagnosis and the NFL talking about sleep apnea. There’s the American Sleep Apnea Association, which is the largest, nonprofit advocacy group. There are the various professional societies that are now redoubling their efforts to educate primary care physicians to ask the right questions. Of course, we’ve invested in our Apnea.com Web site, which is a consumer-education Web site. We have field resources; these are people who are out calling on primary care physicians, cardiologists, pulmonologists, ENTs, other sleep specialists, and making them aware of the signs, the symptoms, and the screening tools for sleep apnea, and the availability of the NovaSom home sleep tests.

Frankly, the payers are playing a big role here as well, because their soapbox is big and their bullhorn is bigger. They play a big role in member communications and provider communications in trying to educate patients just like they do about hyperlipidemia and lifestyle changes such as smoking cessation—a major driver of adverse health events.

MX: Speaking of United Healthcare and Aetna, has it been fairly smooth sailing getting them to agree to pay for home sleep tests? What kinds of questions did you get?

RH: The world has changed dramatically in the last four years or so. In 2008 Medicare published a favorable coverage decision about home sleep testing. Before that, most payers did not acknowledge home sleep testing, or, if it was performed, wouldn’t pay for it. On the heels of Medicare making its decision in 2008 and then the Blue Cross/Blue Shield Association, which is considered a bellwether opinion leader, in 2009 opining that home sleep testing was for real and was accurate and cost effective and what was necessary to address this public health epidemic. On the heels of that most payers have come around and have adopted positive policy for home sleep testing. The world is a very different place now.

MX: The groundwork was laid, in other words, and you’re approaching receptive ears.

RH: Yes.

MX: You mentioned the American Sleep Apnea Association. I understand that Michael Coppola, the president and chief medical officer of the association, has joined NovaSom as the company’s chief medical officer. Was it a long process? How did that come about?

RH: Once we made the decision that we wanted to bring in an industry thought leader, it unfolded pretty quickly. I would say it took less than three months from the time we made the decision until the time we shook hands with Michael. He has been thinking about, and writing about, and lecturing about at-home testing for a long, long time. There are so many things in medicine that take a while to gather momentum. You’ve probably heard the same statistic as me that the average good idea takes 17 years to achieve momentum, and [with] the American healthcare system, as shameful as it is, you hear those words. The time has come, and it certainly felt to us like the tipping point was upon us. And frankly, this also coincides with the sleep community—the sleep centers and the sleep specialists—getting behind out-of-center sleep testing and realizing it was the right thing to do. That it’s accurate, it’s consumer-friendly, and it’s scalable, while it’s not been easy in the short run for them economically because every home sleep test represents a patient who might otherwise have been in their sleep center.

It’s also in the grand scheme of things—and I think they’ve gotten comfortable with this—the way that we can do this more cost effectively so that the payers of America and the employers of America and the consumers of America will feel comfortable about finding the other 15 million people and getting them taken care of, too.

MX: Of 10 patients with a possible sleep apnea problem how many could use your home sleep test and how many would need to go to a sleep clinic?

RH: Almost eight out of every 10 patients that we test turn out to be positive. Our device is unique in that it has the capacity for multiple nights of testing. The virtue of that is there is a false-negative effect associated with any one-night test of sleep apnea. If a holter monitor were only an 8-hour test and you went back to the doctor, and he said, “Well, I didn’t see any ventricular tachycardia,” but then the next time he did it for 24 hours, he’d say, “Yup, I found it.” The first one was a false negative, and it had to do with sample size. [It has to do with] test duration.

We test for three nights more often than not. It depends on what the doctor orders and what the health plan will agree to. But given the fact that the test is comfortable and people are willing to wear it for multiple nights, and frankly there’s not a lot of incremental cost associated with leaving the device in the home for two extra nights, the false-negative rate is relatively low. Very low, in fact. It is not common that patients have to be retested. I won’t say that it never happens, because there are times that patients exhibit the signs and symptoms for sleep apnea, and just like one negative holter test it doesn’t mean you can’t have ventricular tachycardia. But it is not a common problem after multi-night testing.

Before we achieved any traction in the marketplace we published two studies showing night-for-night [testing] compared with an in-facility test that the NovaSom test was equally accurate. When we married that up with the fact that 9 times out of 10 the patients test for 3 nights…we feel very good about the accuracy of our test against any one-night test, be it at-home or in-facility.

MX: What does it mean to have someone of Thomas Fogarty’s stature backing your company?

RH: I’ll tell you what: 30 years ago when I was an intern I was using Fogarty catheters never imagining I’d be doing business with Dr. Fogarty. I don’t have to tell you he is a heavyweight in the device world. In the early days of the company especially when [we were] getting the device right, and all the engineering and manufacturing aspects of this [right], Tom was hugely helpful to the company. Most of that engineering hard work was done before my watch, but it’s the foundation on which our business is built right now.

We’ve been testing patients for 10 years now. The device is tried and true; the patients have a wonderful experience. Their satisfaction scores are extremely high. We’ve never had a significant adverse event with the test. I feel confident in saying that had Tom Fogarty not been involved through those formative years that it’s unlikely that the pathway would have been as smooth once the environment was right and scale was achieved.

MX: During those 10 years and 100,000 or so tests was there anything the company learned that led to product upgrades or improvements?

RH: We did something very significant last year, which is we introduced our next-generation device, the AccuSom. The AccuSom is the first and still the only wireless device used for testing for sleep apnea at home. Unlike every other FDA-approved device, which requires that the device be returned in order for the data to be downloaded and analyzed, we receive that data each morning. What that allows us to do is to help patients through the testing period so if there are any difficulties with testing, or if they simply don’t test despite the doctor’s instructions that they do so, it allows us to be on the ball and make sure the test is completed and that good results are obtained.

Then, on a near real-time basis the physicians can initiate therapy. If the patient completes the test by 7 o’clock, that test can be interpreted by 10 o’clock and that patient can be on the way to getting the therapy he needs. Therapy is like justice. Justice delayed is justice denied. This is an important step in accelerating a critical pathway to the therapy that’s needed.
Is the diagnosis a binary one—in other words either you have sleep apnea or you don’t? Are there comorbidities that need to be ruled out as well?

The diagnosis rests on how many times per hour you observe that a patient is attempting to ventilate unsuccessfully. In our case there’s a belt that goes around a chest wall, and you see that somebody’s chest wall indeed is moving out and they’re trying to breathe. Airflow at the face is reduced or altogether absent, because the airway has collapsed and the oxygen level goes down. How many times an hour does that occur during a recording period? You get a score. That’s called the “apnea-hypopnea index.” There is a score that emerges. Sleep specialists have devised a sliding scale, so you would say 5 to 15 is considered mild, above 15 is moderate, and so on and so forth.

The presence or absence of comorbidities has an important effect on what sleep specialists typically recommend for patients in the mild category. If somebody had no hypertension, no diabetes, no other risk factors, and had an AHI of 6, it’s very likely that a specialist would say, “Let’s keep an eye on this. Here are some things that you could do short of going on CPAP [continuous positive airway pressure] and I’m going to see you again in a little while, and we’ll keep an eye on this.” On the other hand somebody who has an AHI in the mild range but has a family history of heart attacks and has a BMI of 35 and is a Type 2 diabetic, they are likely to say, “No, for you we can’t afford this incremental risk.” The comorbidities do fit into the care plan, which is not to say…the AHI is a number like the BUN [blood urea nitrogen] and creatinine and the heart rate are numbers. What you do with it [depends] on clinical judgment.

MX: Going back to the business side of things, NovaSom is not yet profitable. When do you expect to be in the black?

RH: We think within the next year we’re likely to achieve profitability. Fortunately, we’re very well capitalized right now; we have some great investors. And we have made and are continuing to make a lot of investments in our infrastructure, in our technology, in our sales and marketing effort, so we could control our spend rate right now if we chose to. But given the magnitude of this opportunity that’s available to us and the enthusiasm that our investors have, which is exactly why we raised as much money as we did, we think it’s important for us to step out and step out and try to create this marketplace.

MX: Will you need any more equity funds, going forward?

RH: We think that’s unlikely.
 

MX: A 2010 Frost & Sullivan report says the market for sleep apnea devices is $1.35 billion in 2008 and growing, but there’s a high level of competition. You say NovaSom is the market leader, is that correct?

We do. That reference you made is to the therapy side, so let’s separate diagnosis from therapy. On the diagnosis side most people estimate that there are around 3½ million tests being done a year in this country. [There’s] somewhere near $4 billion, maybe on the outside $5 billion, that’s being spent on those tests. That’s just on the testing side. On the therapy side, which if you add all the money that’s being spent on the CPAP devices and the masks and disposables, that’s probably $2 billion, give or take. One of the funny ratios that you notice is that the diagnosis right now is more costly than the therapy. How bizarre is that? It just speaks to the need to make the diagnosis less of an impediment to patients and to payers alike.
Are there any hard figures or good estimates how much an early diagnosis of sleep apnea could hold down healthcare costs?

There’s a lot of research about this, and we played an important role in one of the most recent publications. Waste Management did a study recently. The primary author was Dr. Ben Hoffmann.

MX: Waste Management?

RH: Waste Management, yes. And I’ll tell you why in just a second. Because they have a lot of truck drivers, and that is an occupational hazard for truck drivers to have sleep apnea. A lot of these guys are big and husky. [Waste Management] undertook the study in which they screened a group of drivers and identified undiagnosed sleep apnea patients and got them on therapy. They published this last year in the Journal of Occupational and Environmental Medicine. What they found is that their paid claims once they went on therapy went down on average about $2800 a year. Those savings came, as you would expect, from strokes and heart attacks. That’s per patient identified.

The interesting part—and this matters a lot to employers—is that they also found five fewer days of absenteeism per year once they went on therapy and about $500 less a year in short-term disability payments for these drivers. That’s just one of many studies. The prevailing thinking about how this all works is the following: When you’re sleeping and you get into REM, or you’re starting to get into the most restful sleep, and your oxygen level goes down, your body reacts to that with adrenaline and cortisol. Knowing what we do about adrenaline and cortisol, that’s not very good for your blood pressure, your heart rhythm, or for your diabetes or your glycemic control. It stands to reason that diabetes, hypertension, strokes, heart attacks, and arrhythmias would be a natural consequence then.

On the other hand, you’d say, “Well, what does that mean for somebody who night in and night out and night in and night out never gets a restful night’s sleep?” It’s no surprise that they would be having on-the-job injuries, accidents, absenteeism, short-term disability, et cetera. There’s a lot of evidence that shows important savings.

MX: I was trying to get a concrete sense of how much those savings might be. Speaking of figures, you’re quoted in the Baltimore Business Journal saying the test costs about 75% to 85% less than a lab test, which you say costs up to $2000. Is that an accurate quotation?

RH: Yes. It’s very unusual for us to not be able to offer a payer 75% or 85% savings per test over a lab test.

MX: You touched on this briefly and I know you weren’t at the company for the development of the home test, but do you recall any developmental challenges for the device?

The challenge that we’ve responded to now has to do with comfort and adoption and usability. I pointed out to you that we…got FDA approval for the AccuSom, which is a next-generation device. The AccuSom is a fraction of the size of its predecessor, so it’s comfortable to sleep with. It’s not much bigger than an iPhone. It straps on to your arm. It can speak 12 different languages. When you turn it on, it will tell you how to set itself up, how to connect the sensors, and what to do so that you’re ready to sleep and test. As I mentioned, it’s wireless. Those are things that we were responding to on the strength of 10 years of feedback from the marketplace.

MX: As an aside, is it a male or a female instructional voice on the AccuSom? Or is it a text?

RH: No, it’s a voice, and it’s female. It’s so funny you should say that because there were a lot of running jokes about exactly what kind of voice we should put into it when we were reengineering this new one. There were a lot of guys in the shop here who wanted Rachel Hunter’s voice or someone like that. It was a running joke. (Laughs.)

MX: I can imagine. And there would be women who want George Clooney’s voice or someone like that.

RH: Absolutely. We went back and forth with that.

MX: As a product development decision, how did you settle on what type of voice you did finally use?

RH: We just got somebody with a voice that was clear and not laden with any particular diction. So they didn’t sound like a Boston Brahmin or a southerner, [for instance]. It was just a generic, clear, comforting voice.

MX: Regarding your background, what led you to your current position as CEO of NovaSom?

RH: All of the businesses that I’ve been involved with since I stopped practicing have been technology-enabled service businesses that were solving a big problem. That’s the common thread in all of them. Here’s an ecosystem where there are 40 million sleep apnea sufferers but the vast majority of them are as yet unidentified. It’s costing us $4 billion-plus a year to test them, and we should be doing it for a fraction of that. This is a big problem for everybody. There are patients out there having strokes and heart attacks and, frankly, dying who don’t need to. There are employers and payers suffering the economic consequences of that. Spouses and children and what-not, so that’s very exciting to me—to have an opportunity to have such a big impact.

MX: What I’m hearing is that this appeals to you as an MD because you can help so many more people combat what you call an epidemic.

RH: No question about it.

This Week in Devices [5/18/2012] - How Can the Medical Industry be more Like Facebook?

How can the Medical Industry be More Like Facebook?

  • In the wake of Facebook's IPO, Forbes' Matthew Herper wonders if the medical industry can inspire the same level of innovation and investment as the social network.
 

Patient's Voices are Changing Medical Devices

Medical Devices Pose a National Security Threat

  • The US Department Of Homeland Security has issued a report stating that medical devices that connect to IT networks could pose a security threat.
 

Medical Devices as Art

  • Artist Revital Cohen's newest project The Immortal is built entirely around reconfigured medical devices.
 

FCC Allocates Wireless Spectrum for Medical Devices

  • The FCC has announced it will set aside a chunk of the wireless spectrum for medical devices – making the U.S. The first country to do so.