Using Simulation as Digital Evidence for FDA Approval


Simulation can be used in a variety of ways in medical device applications. These include performing in silico (virtual) device testing or as part of algorithms within software embedded inside a device.

Simulation provides multiple benefits for the medical device industry and the patients it serves. Unsurprisingly, considering these benefits (all of which we cover in this article), the FDA is keen to leverage simulation to advance regulatory science.

The challenge for the medical device industry is demonstrating that their simulations provide sufficient “digital evidence” for FDA approval. According to the FDA, submissions “often lack a clear rationale for why (computer simulation) models can be considered credible for the context of use.”

This article explains the steps medical device manufacturers can take to boost simulation credibility and bring more innovative products to market faster. For the sake of healthy innovation, we must all do whatever it takes.

A Brief History of Simulation in the Medical Field

Medical simulation has a long history, dating back to ancient times when models of human patients were built to demonstrate the effects of diseases and animals were used for surgical training (as is still the case). In the 18th century, birthing simulators were used to teach midwives and surgeons the latest techniques. 

In the early 1960s, plastic toy manufacturer, Ausmund Laerdal, created Resusci-Anne, the most widely used CPR mannequin of the 20th century. By the late 1960s, the first computerized mannequin, Sim One, was born. Developed at the University of Southern California, Sim One later morphed into a more affordable simulator called Harvey (which made realistic heart and lung sounds!)

Fast forward to 2023, and thankfully, things have moved on. Computer modeling in biochemical engineering can reliably simulate everything from the patient flow in emergency rooms to the behavior of chronic diseases in a specific population. They can also be used to support regulatory submissions.

The Use of Simulation in FDA Approvals

The use of computer modeling and simulation (also known as “in silico” methods) in regulatory submissions is well established and rapidly increasing in line with Moore’s Law. Below are two of the most common ways this technology is used when seeking FDA clearancel for medical devices.

In Silico Device Testing: This is when computational models simulate medical devices to demonstrate safety and/or effectiveness. Device testing models can be paired with patient models to simulate device performance under representative in vivo conditions.

In Silico Clinical Trial: This is when device performance is evaluated using a ‘virtual cohort’ of simulated virtual patients with realistic anatomical and physiological variability representing the indicated patient population. 

The Benefits of Simulation (In Silico Trials) of Medical Devices

In silico testing is a powerful tool for evaluating the safety and performance of medical devices before they’re manufactured and introduced into the market. Whether the intention is to complement or replace physical trials, the in silico trial approach offers manufacturers several benefits over traditional testing methods. Below are some examples.

  1. In silico testing enables manufacturers to analyze a medical device’s performance in a controlled environment without the interference of external factors present in physical bench tests. This results in more accurate and reliable performance assessments.
  2. In silico testing accelerates the market launch of new medical devices by leveraging the high speed of computer simulation, allowing manufacturers to run thousands of tests in just seconds.
  3. In silico testing is considerably less expensive than physical alternatives.
  4. In silico testing enables manufacturers to simulate and examine edge cases, providing a comprehensive understanding of how a medical device performs in extreme conditions.
  5. In silico testing can uncover unexpected adverse events that may go undetected in limited study samples but frequently occur within the target population.
  6. In silico testing allows manufacturers to detect design limitations early, streamlining the development process, reducing costs, and expediting the availability of life-saving medical devices for patients.
  7. In silico testing reduces the cost and time associated with the pre-market evaluation of medical devices, enabling manufacturers to experiment with more high-risk products. This, in turn, drives innovation and advances in the field.
  8. In the event of a post-market failure, in silico testing allows manufacturers to quickly identify the root cause and restore the performance profile of a medical device.
  9. In silico testing reduces the likelihood of encountering functional issues with expensive hospital equipment, reducing capital expenditure and ensuring reliable operation.

The FDA Explains How to Demonstrate a Simulation Model is Credible for FDA Approval

Manufacturers of medical devices need to demonstrate their simulation models’ credibility to gain FDA approval. Fortunately, the FDA provides a nine-step process to follow (the Generalized Framework for Assessing Credibility of Computational Modeling in a Regulatory Submission.)

You can read about the nine steps (at length) in Assessing the Credibility of Computational Modeling and Simulation in Medical Device Submissions, published in December 2021. Or just read a brief summary below:

Step 1. Describe the specific question, decision, or concern to be addressed in the regulatory submission.

Step 2. Define the context of use (COU) of the computational model. The COU is a statement that defines the specific role and scope of the model.

Step 3. Determine the model risk (the possibility the model and simulation could be wrong.)

Step 4. Identify any credible evidence that supports the credibility of the computer model for the COU. 

Step 5. Break down the analysis of verification, validation, or other sources of this credibility evidence.

Step 6. Perform a prospective adequacy assessment–if goals are achieved, will the credibility evidence be sufficient to support using the model for the COU?

Step 7. Execute the study.

Step 8. Perform a post-study adequacy assessment–does the credibility evidence support using the model for the COU?

Step 9. Prepare a report.

In Conclusion

Simulation offers a powerful digital solution for manufacturers of medical devices, delivering increased accuracy, enhanced product design, improved safety, and reduced cost and time compared to traditional testing methods. 

By leveraging simulation, manufacturers can achieve FDA approval for their products and bring safe, effective medical devices to market faster. But for simulation models to be considered credible digital evidence by the FDA, manufacturers have to jump through the hoops outlined in the Generalized Framework for Assessing Credibility of Computational Modeling in a Regulatory Submission.

If you want to learn more about simulation and its use in FDA approvals, get in touch with us at KETIV. We’ll happily talk you through everything you need to know.

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