FDA Releases Computational Modeling and Simulation Guidance

FDA recently released draft guidance as a reference for assessing the credibility of computational modeling and simulation (CM&S) in medical device submissions, aiming to facilitate a consistent and efficient review process. The recommendations apply to physics-based, mechanistic or other first principles-based models.

FDA’s guidance comes as the use of CM&S in regulatory premarket submissions has been increasing on a steep trajectory in recent years. Considered a revolutionary tool for the orthopedic industry thanks to its ability to speed development and regulatory decision-making, CM&S makes it possible to build a model of a patient’s body systems and a medical device and run simulations to determine the device’s performance.

FDA’s guidelines recognize the many benefits of CM&S and aim to increase its use. A primary benefit is the ability to detect significant adverse effects that would not be detected in traditional in vivo or in vitro assessments. Ultimately, FDA’s guidance aims to increase the trust in CM&S in premarket submissions through a consistent methodology and assessment parameters.

CM&S Guidance Outline

The document outlines a variety of ways industry can use CM&S for medical device submissions, including:

• In silico device testing
• Use within medical device software
• In silico clinical trials
• CM&S-based qualified tools

No matter how CM&S is used, it’s necessary to demonstrate that the computational model itself is credible. According to FDA, “methodologies for model credibility assessment have been established in the scientific literature and continue to evolve.” To demonstrate model credibility, one conducts various activities, including verification, validation, uncertainty quantification, applicability analysis, and adequacy assessment.

Using the FDA-recognized standard ASME V&V 40 Assessing Credibility of Computational Modeling through Verification and Validation: Application to Medical Devices, FDA provides the following guidance for orthopedic companies using CM&S in their premarket submissions:

1. Describe the question(s) of interest to be addressed in the regulatory submission that will be informed by the computational model.
2. Define the context of use (COU) of the computational model.
3. Determine the model risk.
4. Identify and categorize the credibility evidence, either previously generated or planned, which supports credibility of the computational model for the COU.
5. Define credibility factors for the proposed credibility evidence and set prospective credibility goals for each credibility factor, with a plan to achieve these goals.
6. Perform prospective adequacy assessment: if the credibility goals are achieved, will the credibility evidence be sufficient to support using the model for the COU given the risk assessment? If YES: continue to Step 7. If NO: you may need to modify the model, reduce the model influence, modify the COU or revise the plan to generate credibility evidence. If any changes are made at this stage, go back to Step 2.
7. Generate the credibility evidence by executing the proposed study(ies) and/or analyzing previously generated data.
8. Determine if credibility goals were met and perform post-study adequacy assessment: does the credibility evidence support using the model for the COU given the risk assessment? If YES: continue to Step 9. If NO: you may wish to modify the model, reduce the model influence, modify the COU or collect additional evidence. If any changes are made at this stage, go back to Step 2.
9. 9. Prepare a report on the credibility of the CM&S for inclusion in the regulatory submission.

Visit the FDA website to download the guidance document draft in full. Industry can submit questions until February 22. Save Supplier