Certification of implantable devices can be challenging, but partnering a knowledgeable outside expert can help accelerate the process. Here is an inside look at how similar partnerships worked for four manufacturers of highly diverse devices.
Minimizing Safety- and Security-Related Design Problems
Aside from providing the benefit of anticipating changes to standards and regulations, Underwriters Laboratories (UL) technical experts also work with medical manufacturers to help them approach product design and development challenges.
Anura Fernando, Principal Engineer for Medical Systems Interoperability and Security at UL, works directly with manufacturers to help them tackle many of the challenges they face. These include miniaturization, component selection, use of smart sensors, MEMs, and how to plan ahead for the best defense in cybersecurity; avoiding vulnerability traps for data-linked devices.
“At UL we strive to facilitate rapid market adoption of new technological solutions,” Fernando says. “We can suggest different design strategies, different architectural constructs and different approaches to enhance both device capability and security. This can help minimize cost and help manufacturers get their products onto the market quickly.”
“We help them look at it from the point of view of how can this product fail and what can make things go wrong? How can it hurt the patient? What can someone who is malicious do to make this product do what it is not intended to do?”
“If manufacturers incorporate this concept through the entire development process, they can minimize their exposure to safety and security issues later in the product lifecycle. They will already have the tools they need to quickly identify field problems in what could be very complex systems that might otherwise take months or years of engineering analysis to troubleshoot. If you wait until the end to test a final product and run into a problem—it can be extremely time consuming and costly.”
This is the path that the following companies kept as a guide when developing their latest implantable technologies.
A Better “Heart” for ICDs and CRTs
Boston Scientific, Marlborough, MA, USA, has a large medical device portfolio, including implantable electronic medical devices. Dr. Dave Knapp, Vice President, Research & Development, says that their EnduraLifeTM Battery technology (Figure 1) was a critical innovation for extending the life of their cardio-defibrillators (ICDs) and Cardiac Resynchronization Therapy (CRT-D) devices.
“Existing devices would last approximately three to five years before needing to be replaced. The question was how do we increase that lifetime significantly and still keep the device at an extremely manageable size?” he says. “What we developed is a battery that lasts twice as long, and is also 11 percent smaller. This was done through internal innovation and also collaboration with external stakeholders such as the FDA.”
“Once we knew our goals, we moved into building prototypes. We tested them, analyzed the results, and then ran this loop as fast as possible. Risk analysis and quality systems are at the heart of this work. Risks are identified, both the severity and the occurrence. That dictates what kind of testing is needed to verify and validate that devices will work as they should. For this specific device, this took more than five years. It was a combination of excellent design work done at the chemistry level, the physics level, and then combining that with advanced manufacturing techniques to ensure repeatability which is key to the reliability,” Dr. Knapp explains.
“To test prototypes and then make improvements, we had to be able test in an accelerated manner but in a way that would tell us if the battery would be reliable throughout its life, without speeding it up so significantly that it might make the test irrelevant. That was a challenge.”
“Our teams don’t operate in a vacuum,” he adds. “We operate within a business structure. These development teams are not just R&D and tech people. They are also collaborating all along the way with marketing, clinical, all of the regulatory and certification entities–in concert.”
“As the market moves to a more value-based health care system, reducing the number of procedures a patient must go through is not only better for the patient from a health perspective, it is also less costly, “Dr. Knapp says, He adds, “This project not an isolated example, it’s how we approach everything at Boston Scientific.”
EnduraLife battery technology has been FDA certified for over a decade, but it is important to note that it has taken this long for the actual value of this technology to be recognized.
Reinventing a “Living Stent”
Based in Milpitas, Ca, Elixir Medical Corporation specializes in the development of drug device combinations; primarily stents for the treatment of cardiovascular and vascular disease. Motasim Sirhan, CEO, explains that the company’s objective is to move the cardiovascular stent industry into the next frontier of intervention through the development of stents and scaffolds that are capable of adaptive remodeling and pulsatility mimicking the normal function of arteries.
“Current stents re-establish blood flow, but they typically cage (jail) arteries, prohibiting them from exhibiting their normal adaptive remodeling and pulsability functions, potentially accelerating disease progression and causing clinical events over time,” he says.
To counteract these issues, Elixir developed a biodegradable stent, called the DESolve scaffold (Figure 2 ).“Developing stents capable of opening arteries in an optimal manner and yet allowing arterial normal function to resume has been a difficult task and eluded serious efforts for over 30 years,” Sirhan says. “Elixir’s DynamX made this a reality.”
It took “thinking outside the box”, appreciating and learning from Drug Eluding stents (DES) and scaffolds. The design, prototyping and testing took over two years and underwent over 150 different iterations to end up with DynamX. Testing included bench testing, Finite Element Analysis (FEA) testing, computer simulations and extensive preclinical evaluations before beginning a clinical study.
“We didn’t have the right equipment to make the first prototype so, it took us weeks just to get a first semi-working prototype. When we tested it, we realized the true potential of this technology. It was very exciting to know that we were at the cusp of a game changing technology.”
DESolve scaffold technology demonstrated arterial adaptive remodeling within six months (mimicking the normal arterial function), and achieved excellent long term clinical results through five years follow up, well beyond the break down of the scaffold into body-friendly components of CO2 and water.
“Elixir Medical is the only company to succeed in developing stents and scaffolds capable of resuming the normal function of arteries after intervention. We believe this will transform the cardiovascular and other vascular industries alike,” Sirhan concludes.
Drug-Resistant Epilepsy Meets Its Match
While LivaNova’s VNS Therapy System has little competition in the area of implantable devices for the treatment of epilepsy, drug-resistant epilepsy has been a challenge. According to John Murphy, Vice President of Research & Development, their latest VNS Therapy System, SenTiva™ (Figure 3), a technology to treat drug-resistant epilepsy is unique in the space.
“It is the smallest and lightest responsive therapy for this type of epilepsy control on the market, and the only device that treats epilepsy, also permitting both 1.5 and 3.0 Tesla MRI scans to be performed. The device delivers regular, timed stimulation to the vagus nerve that can interrupt seizure activity in the brain. Stimulation is also delivered on demand in a closed loop manner using detected changes in the heart rate that may be associated with seizures,” he explains.
The device is implanted under the skin under the clavicle during a minimally invasive outpatient procedure; a second incision is made in the lower neck and the lead from the device is wound around the vagus nerve in the neck. The device is the size of the smallest cardiac pacemaker on the market.
“Added features and drastically reduced device size, created a ‘ground-up’ development. We couldn’t use our old circuits, our old firmware or software that goes into the Implantable Pulse Generator (IPG),” Murphy says.
“We started with mathematical models and generated simulations to understand how the circuits would act, how much current the components would use and developed performance information. Then we moved to breadboards where we explored each of the various functions and had access to all the needed signals. We used the data taken at this stage to validate that the models were correct.”
“From breadboards, we moved on to full electronics, doing extensive testing on them and reconciled models with results until we had a match. The final stage consisted of verifying and validating final products.”
Murphy says that they kept in communication with the FDA and DEKRA during all development process steps. “Our strategy was to work with them from the start. We’ve developed very good working relationships with all regulatory bodies. This enabled a cost effective and timely path to bring the product to market.”
The therapy system features a wireless wand, a small tablet programmer, and the next-generation IPG that connects to a lead with a stimulating electrode. Together, these components offer patients with drug-resistant epilepsy a physician directed, customizable therapy. LivaNova’s latest SenTiva™ technology debuted on the U.S. market October 2017.
Taking the “Tingle” out of Chronic Pain Relief
Traditional chronic pain relief systems implanted in the spinal epidural space, use 10 to 100 Hz stimulation per second causing paresthesia or a tingling/buzzing sensation in the extremities to mask pain signals that travel from the extremities to the brain and back. While masking the pain, this can be uncomfortable causing problems when driving or sleeping.
Nevro (Redwood City, CA USA) put a totally 21st century twist to into this aging technology. Chris Christoforou, Vice President of Research & Development says that what Nevro did was consider how the body would react to pain stimulation frequencies of 10,000 Hz.
“Externally, the new and old systems are similar, but internally the difference is an innovation,” he says. “The electronics, the firmware logic and specific components; all that is needed to safely deliver a therapy at 10,000 Hz is the difference.”
“Engineers took a goal, visualized a design and then applied real world technology to it to see if the goal was feasible,” Chris says. “We had to consider many parameters of the device such as size, shape, battery life, and others which could limit our possible set of solutions.”
“We found outside experts to help us, including consultants, industry experts and test labs. We also used the expertise of those in printed circuit boards, batteries and machining. Working on a miniature design level added extra challenges. But, the continued technological evolution of miniaturized electronics, components and systems is opening up new worlds of device potential all across the medical industry.”
Chris explains that after implantation, the new device (Figure 4) is controlled externally using radio communication. For many chronic conditions such as in a progressive disease, pain may also be progressive. Nevro partners with the physician to modify parameters of the therapy that are variable, to achieve optimum pain relief for the patient for many years. “It is a very safe device. The safety levels we had to prove to the certifying bodies in the U.S. were extremely high.”
Nevro high-frequency HF10 therapy is approved in the USA, Europe and Australia. Chris adds that the company has been receiving positive feedback from patients, because with the pain relief, there is no irritating sensation that affects normal activities, including a good nights sleep.
From the UL point of view, Anura Fernando concludes, that while all mature medical device manufacturers have already factored “end-of-life”, or more precisely, “end-of-support”, into new product roll-outs right up front, many new manufacturers in the medical area do not understand full product life cycle thinking.
“Some need help in understanding the true scope of complete product development, including the latter phases of the product life cycle and how to handle those. We are there at the beginning and also to help them find the best way to handle the end.”
From concept to end of life planning, medical device companies and certification bodies like those above, continue to combine their talents to ensure that all efforts that go into developing unique medical devices will continue to evolve and safely serve the needs of an evergrowing marketplace.
Sidebar: Contributor Contact information
Dr. Dave Knapp,Vice President, Research & Development
300 Boston Scientific Way
Marlborough, MA 01752-1234 USA
Elixir Medical Corporation
Motasim Sirhan, CEO
920 N. McCarthy Blvd. Suite 100
Milpitas, CA 95035 USA
Vice President of Research & Development
20 Eastbourne Terrace
London, W2 6LG United Kingdom
Vice President of Research & Development
1800 Bridge Parkway
Redwood City, CA 94065 USA
MHealth, UL (Underwriters Laboratories)
333 Pfingsten Road
Northbrook, IL 60062 USA