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The group of industries known as Life Sciences – biomedical devices, diagnostics and pharmaceutical – is seeing unprecedented change in how new medicines and technologies are being developed. The industry leaders here are increasingly turning to numerical simulation and modeling to reduce costs, lessen risks, foster innovation, augment diagnostics and trials and create better products. Still, the adoption and proliferation of Computational Modeling and Simulation (CM&S) in Life Sciences is at a nascent stage. The major challenge here is that this is a highly regulated industry and as such, the vendors and users alike are looking up to the regulatory agencies for guidance on incorporating Computational Modeling and Simulation (CMS) into the total product life cycle.

The Medical Device Innovation Consortium (MDIC) is the first-ever Public Private Partnership (PPP) independent organization to advance medical device regulatory science and to bring CM&S into regulatory decision making. CD-adapco’s Director of Life Sciences, Kristian Debus sat down with Dawn Bardot, Senior Program Manager, Modeling & Simulation at MDIC to understand their vision to place CM&S as regulatory grade evidence in the United States and how simulation vendors can help with this vision.

Kristian: Thanks for talking to us, Dawn. What exactly is the role of MDIC?
Dawn: MDIC, formed in late 2012, is a public private partnership between industry, government (including FDA, Centers of Medicare and Medicaid, National Institute of Health) and other interested parties, software manufacturers and medical device manufacturers. Our vision is to create an opportunity for all the stakeholders to come together and collaborate on regulatory science. If we are to meet the 21st century demands and technologies, we have to find new ways of demonstrating device safety and cost effectiveness. We have three projects at MDIC that identify new methods and tools for demonstrating medical devices. The Patient Centered Benefit Risk (PCBR) assessment project is looking at bringing the patient’s voice and needs into medical device assessment. The Clinical Trial Innovation & Reform (CTIR) project focuses on bringing US products faster to market as well as ways to do more simple trials based on electronic medical records and collected data. The last is the Computational Modeling and Simulation (CM&S) project to facilitate the use and acceptance of simulation tools in the regulatory review process.

Computational model of a heart valve

Kristian: Where can CM&S tools help the most in the regulatory review process?
Dawn: We now have the ability to rely on CM&S for business decisions and root cause analyses. But the use of CM&S is not prevalent in the areas where the medical device companies face major expenditures: clinical trials and reimbursement. Clinical trials account for 50% of the cost to bring the product to market but numerical simulation, which can keep these costs down, is not being used. The other biggest opportunity is in the reimbursement stage where these models can be used to answer questions for the reimbursement agencies.

Kristian: So MDIC wants to foster the cooperation and communication necessary to achieve these goals for CM&S?
Dawn: Yes. There’s no other place where all of the stakeholders can collaborate and talk about how to overcome these barriers. There are other professional trade organizations but MDIC is the only one that’s really focused on that collaboration as a 501(c)3 non-profit organization.

Kristian: So how close are the other two groups working with the CM&S group? There seem to be mutual benefits here.
Dawn: It’s absolutely right that all three project groups of MDIC should have overlap. For example, the CM&S working group recently had a presentation at a workshop hosted by the CTIR project. The presentation showed that by using virtual patients from CM&S, the number of real patients necessary in a clinical trial can be reduced. In addition to demonstrating the device in a safe, effective and faster manner, CM&S can also augment trials where recruiting real patients is difficult. This is a great example of collaboration between these two projects. The PCBR project recently released their framework document. A major focus was on demonstration projects for evaluating a patient’s preference or a population of patients’ preference or risk tolerance for medical devices. Here, the willingness of patients to use devices that have been demonstrated through virtual patients can also be used as evidence to support bringing the device to market.

Computational model of a stent

Kristian: What are some popular application areas of CM&S right now?
Dawn: A lot of the use has been in analyzing blood flows and in respiratory analysis. Then there is the biophysics component – devices that are either interacting with the human or implanted in the human. Outside, there are external components of the medical device process that are of interest, things like dialysis machines. In the qualification of devices, modeling the manufacturing process and understanding the risk and liability is becoming important. In the total product development cycle, CM&S can be informative in multiple aspects.

Kristian: Do you see applications in diagnostics and patient monitoring as well?
Dawn: Absolutely. Increasingly, there will be opportunities for CM&S to help inform citizen scientists, whether it is in the context of medical devices or health apps. For example, asthmatic systems are trying to understand triggers and the need for an inhaler. Environmental conditions are crucial here. Based on big data, these systems can predict triggers but they can also rely on atmospheric condition models to monitor environmental changes. The predictive understanding from CM&S and the empirical observations from big data can come together to work for health apps and medical devices. It will be interesting to see where the discussion goes around diagnostics using CM&S. Modeling can play a supporting role in treatment planning, interventional planning, device positioning, etc. CM&S can also help in the physician training realm.

Kristian: At CD-adapco, our current focus is on multidisciplinary, multiphysics simulations in STAR-CCM+. How important is this in regulatory science?
Dawn: I think it’s really important for the code manufacturers to consider multiphysics. Medical devices are natively multiphysics-oriented with the interaction between the biological and engineering component.

Kristian: What are the biggest challenges for current tools to be accepted in regulatory decision making?
Dawn: Last year, MDIC asked our members about the biggest hurdles in using CM&S at the regulatory stage. Return on investment and the specialization needed to use CM&S tools were some popular answers but the majority found regulatory uncertainty as the biggest hurdle. We can get around this by having examples where CM&S is leveraged at regulatory stage and making this information public. Also, demonstration projects to showcase the utility and credibility of CM&S in the regulatory phase are needed to overcome this uncertainty.

Computational model of a neo-natal unit

Kristian: So it is a chicken and egg problem. The regulatory body wants to see more modeling and examples from the industry while the industry will start going in that direction only if the FDA requires CM&S.
Dawn: It is less about CM&S being required by the FDA and more about the vendors wanting to understand the expectations by the regulatory agencies. More examples and use from vendors will help the FDA explore framework and validity and offer feedback on CM&S tools. Currently, such collaboration occurs one-on-one between a sponsor/vendor and the agency. What we need is a grand challenge that can bring together academics, industry and regulators; a challenge similar to the race to the moon or the genomic project that is given to the community. I think the community would rise to that challenge. We need to identify what the “moonshot” challenge for this community is.

Kristian: What about the conflict of interest for commercial vendors in collaborating?
Dawn: We have to recognize that in this complex space, none of us have all the tools and knowledge to go alone. We have to explore a cooperation model to fiercely compete but collaborate where the information is shareable.

Kristian: Do you think the technology from the vendors is ready right now to tackle these challenges?
Dawn: Absolutely. CM&S has been used in regulatory submission for decades. In angioplasty, there was a device approved for market based solely on simulation. The technology from code manufacturers is ready. The people using these technologies are ready. MDIC wants the stakeholders to know that modeling is ready to use. Our goal is to find a grand challenge for the community so we can establish verification and validation benchmarks and foster cooperation.

Kristian: What’s your advice for end users and the vendors?
Dawn: Start using CM&S throughout the entire product development cycle more frequently. You can enrich and validate the models at every step and document this to start developing the processes. Credibility of the models and documentation of the processes is important. We have seen surprising openness from the code manufacturers to collaborate and work together. Most of the end users are single user or smaller teams and the code vendors can help them through established processes, automated scripts, cloud-sourced HPC nodes, code verification suites and so on. Vendors like CD-adapco can support both end users and regulatory organizations in this journey.

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