When Edwards Lifesciences set out to design the first generation of its transcatheter implantable heart valve to skip open-heart surgery for valve replacement, the process took nine years from initial steps to acceptance by regulators. Eleven years later, using the latest modeling and simulation technology early in the design process, the third-generation valve took less than half the time from the drawing board to regulatory approval.
“The structure was almost completely redesigned, but we are able to do it faster by making design modifications more efficient, leading to significant improvements in clinical performance and dramatic procedure simplification,” said Hengchu Cao, senior director of engineering at Irvine, California-based Edwards Lifesciences. “More importantly, we were able to make a lot of improvements, help more patients and create a greater community for combating heart disease.”
The key to the time savings? Scientifically accurate 3D simulation of the heart valve, to understand and manage opportunities and challenges. Simulation began in the early concept stage, where engineers were able to virtually model what happens to blood flow in the human body when there is stenosis, an obstruction in the aorta, and regurgitation, which is leakage from the aortic valve. Then they were able to simulate what changes occurred when the artificial valve was implanted, revealing how blood flow would be affected and predicting how the heart would respond.
“The simulation enabled us to know what was going to happen when we intervened with a device, what changes would take place in the body and how they will affect the overall anatomic structure and physiology,” Cao said.
Growing adoption of modeling and simulation (M&S) in health care creates the potential to bring more medical devices to market more quickly, with improved designs and improved understanding of how the devices will affect the body. After studying the potential of M&S in 2018, in fact, the American Society of Mechanical Engineers (ASME) found that the technique “promises to revolutionize the medical device industry.”
ASME cited three main benefits: reducing costs, increasing confidence in devices by increasing the number of tests that can be performed, and making it “possible to conduct tests that would not be feasible in the physical world because of practical limits on testing in humans or because of the difficulties presented in testing sophisticated equipment.”
REGULATORY ACCEPTANCE
In the medical device field, simulation offers so much promise that the U.S. Food and Drug Administration has sponsored a Medical Device Innovation Consortium to promote the use of simulation to better assess devices involving the heart and blood vessels, orthopedics, blood damage, and even of brain stimulation and MRIs, which can heat the body.
The technology “can give us higher confidence in medical products, especially if they’re thoroughly evaluated on the computer, because we can perform an infinite number of simulations,” said Tina M. Morrison, regulatory advisor for the FDA Center for Devices and Radiological Health. “It can reduce our reliance on animal models and human data, and reduce costs and speed innovation. These benefits will enable M&S to revolutionize medicine the way it has other fields.” She noted that the FDA has issued guidance on how companies can use modeling and simulation studies in regulatory submissions and is developing standards for verifying and validating if the results are accurate.
The consortium also is working to develop a “virtual patient,” a simulation of the entire human body that can be adapted to reflect different health conditions. The virtual patient would permit researchers to simulate what happens when a particular device is implanted in thousands of different people, reducing the need for large human clinical trials. Among the devices being developed is an artificial pancreas with built-in simulation technology that can measure a patient’s glucose levels and decide what therapy should be delivered to the patient, Morrison said.
THE JOURNEY FROM MANUFACTURING TO MEDICINE
While computer modeling to create and test all types of product designs has been available for several decades, it generally produced only a geometrical design or shape of an object. The real breakthrough has been the addition of simulation capabilities, which creates a mathematical model of the geometrical design. This scientifically accurate mathematical model can then be used to test the design virtually – and operate it in a simulation of the actual environment where it will be used. This allows researchers to try and perfect many variations of a design before building a physical prototype.
The aircraft industry has used simulation software for decades to test the endurance, flexibility and stress on parts of aircraft. Now, life sciences simulation software adds chemical and biological elements to the mathematical models for simulation of medical devices. The software uses real-world data to calibrate the mathematical models.
For example, in designing a stent to open a blocked artery, the engineer must simulate not only the stent, but also how it interacts with the blood vessel, a process known as boundary conditions. Unlike cars and airplanes, which are virtually identical when manufactured, each human is physically and physiologically different. Which means that a simulation must be able to adapt to the biology of an individual blood vessel – reproducing how elastic and durable it is – along with the elaborate chemical processes that make a heart beat.
“The combination of high-performance computing with all the large data sets available is really turbo-charging innovation and accelerating the process of bringing a product to market,” Edwards’ Cao said.
AN INSIDE VIEW
Ashley Peterson, who heads the life sciences division of Thornton Tomasetti, a US-based consulting firm, says that one advantage of simulation is its ability to complement the physical bench-testing companies are required to perform as part of the regulatory approval process.
“You can do things in modeling and simulation that you can’t do in a bench-top test,” Peterson said. “You can look internally into a structure, which might be hidden from view on a benchtop test. When you’re using the tools, you’re actually solving the underlying physical equations so you can look at what’s happening with different elements of the design.”
When using simulations to provide device design information, one has to make sure the simulation output is correct. To do this, simulation validation is used. Validation is the process of assessing the how well the computational model represents of the reality of the physical situation said Peterson.
“One of the biggest benefits of using modeling and simulation has proved to be the ability to adapt and test designs to make sure they are compatible with all the variations that arise in human anatomy.”
Ashley Peterson, Life Sciences Division Head, Thornton Tomasetti
While modeling and simulation accelerate the design process, saving time and money, Peterson said that another big advantage of performing simulation early in the design process is that it can provide previously unknown information. For example, if a proposed design is not producing the desired results, he said, simulations allow the researcher to probe deeper, changing certain aspects of the design to see how the results change.
“You get a greater understanding; and therefore, the time it takes to final product delivery is actually faster,” Peterson said.
One of the biggest benefits of using simulation is its ability to adapt and test designs to all the variations that arise in human anatomy. “For example, you can say you want a design to work for 60% of people who have a particular need” Peterson said. “You can try it on all of the possible variations you might expect in the human body.”
What’s more, the future for expanding the use of modeling and simulation in life sciences seems especially bright. As the software gains wider adoption, it will be able to move upstream and downstream from the development stage. For example, instead of looking just at the design of a device, Peterson expects M&S can help researchers identify previously unexpressed requirements that doctors and others who use a device might have for it. It also will be able to simulate how the device is used in a range of different patients and get a clear sense how the patients would respond to the device, even before a physical model is built and tested.
“Instead of tweaking just one aspect, you’ll be able to say right from the get-go that you can add value, right up to the end when the device is actually being used by people,” Peterson said.
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