What can we do to get exciting medical breakthroughs to patients faster? It’s a question we ask ourselves every day at the US Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH).
Our role is to protect and promote public health by providing access to high-quality, safe and effective medical devices. This is no easy feat: We oversee approximately 175,000 medical devices on the US market; and each year we receive about 22,000 submissions for new technologies. The devices we regulate range from low-risk products to life-saving devices that include heart valves, total hip replacements, vascular stents and blood pumps.
Developing and testing these devices is a rigorous process. However, expensive and lengthy clinical trials and animal studies are burdensome and can delay the regulatory evaluation of innovative technologies—a delay that, in some cases, might mean the difference between life and death for a patient. We’re dedicated to eliminating those delays, but speed must be achieved safely.
Simulation promises change
Sophisticated, scientifically based computer simulation could be the key. Advances in simulation capabilities and accuracy have the potential to move us away from approvals mainly based on a single source of data (for example, a single clinical trial designed to understand safety and effectiveness in the representative patient population) to a future where historical, prospective and concurrent data can be used to understand the efficacy and performance of medical devices, along with more robustly relying on data from digital evidence, such as computational modeling.
What’s more, if it can be proven that virtual, simulated patients can accurately replicate important and relevant aspects of real, living subjects, then future clinical trials may be able to rely, at least in part, on virtual subject simulations. This may lessen the need to test new devices on real human subjects, while also reducing the need for animal testing.
These simulated trials, known as in silico or “in-the-computer” trials, already show great promise. Consider a recent submission to the FDA for an advanced breast-screening system, which relied on a clinical trial involving 400 female subjects who received double exposure to ionizing radiation over many years. Computer- simulation tools, developed by the FDA, were used to perform a fully in silico trial involving 2,986 virtual, simulated subjects. The simulated trial results were consistent with the actual clinical trial—simulation matched reality.
We’ve also recently seen in silico trials used to confirm the safety of a new, next- generation pacemaker and to support the approval of Mirvaso, a topical gel for the treatment of various skin conditions.
A new wave of innovation
Our next step is a big one: We’re collaborating with cardiovascular researchers, educators, medical device developers, regulatory agencies, software developers and practicing cardiologists on the Living Heart Project—a breakthrough initiative that will see the development of highly accurate, personalized digital human heart models, which could establish a foundation for cardiovascular in silico medicine.
Through this initiative, pacemaker leads and other cardiovascular solutions will be designed, manufactured and tested both physically and virtually. The trial will feature the use of physics-based computational models and simulations of the devices, constructed to replicate a virtual patient population. We will design the clinical trial with information collected from real subjects, but in a virtual environment.
TINA MORRISON
Our ultimate aim is to create a pathway for digital evidence—in the form of virtual patients—to replace clinical evidence, where appropriate. The goal: to significantly reduce the time, cost and risk associated with human clinical trials, bringing life-saving solutions to market faster.
Transforming the review process
The current review process for medical devices is the best we’ve had to date but it’s inefficient—a one-way system in which manufacturers submit static, paper-based documents.
But imagine if manufacturers could invite FDA regulators into their collaborative product innovation platform on the cloud. There, wearing augmented reality headsets, regulators could interact or “experience” the device for themselves in a simulated environment, leading to a more robust, efficient and transparent review process.
By reducing the time required for each regulatory stage, while still assuring robust evidence generation and high-quality decision making, in silico reviews should help vulnerable patients get faster access to safe and effective medical technologies. We’ll also reduce the need for physical testing and in vivo studies, reducing the burden on both animals and patients.
The transition from real to virtual won’t be easy or quick. We need knowledge from the clinical setting to make accurate models, and that means we’re embarking on a long journey. It’s a journey, however, that has the potential to reduce or eliminate the need to use both animals and people as test subjects, while bringing better treatment options to patients sooner.
I’m proud that the FDA is leading the charge, and we look forward to sharing our learnings with regulators and industry professionals worldwide.
PROFILE: Tina Morrison is Director of Regulatory Science and Innovation at the US Food and Drug Administration (FDA). In 2016, she led an agency-wide working group on modeling and simulation, which led to the FDA’s breakthrough guidance for modeling medical device submissions. In 2019, after leading the American Society of Mechanical Engineers’ team in drafting procedures for evaluating computational models of medical devices, the FDA chose her as its Federal Engineer of the Year.
