Trial Approach for Biomedical Products: A Regulatory Perspective.

The modern pharmaceutical industry is transitioning from traditional methods to advanced technologies like artificial intelligence. In the current scenario, continuous efforts are being made to incorporate computational modeling and simulation in drug discovery, development, design, and optimization. With the advancement in technology and modernization, many pharmaceutical companies are approaching in silico trials to develop safe and efficacious medicinal products. To obtain marketing authorization for a medicinal product from the concerned National Regulatory Authority, manufacturers must provide evidence for the safety, efficacy, and quality of medical products in the form of in vitro or in vivo methods. However, more recently, this evidence was provided to regulatory agencies in the form of modeling and simulation, i.e., in silico evidence. Such evidence (computational or experimental) will only be accepted by the regulatory authorities if it considered as qualified by them, and this will require the assessment of the overall credibility of the method. One must consider the scrutiny provided by the regulatory authority to develop or use the new in silico evidence. The United States Food and Drug Administration and European Medicines Agency are the two regulatory agencies in the world that accept and encourage the use of modeling and simulation within the regulatory process. More efforts must be made by other regulatory agencies worldwide to incorporate such new evidence, i.e., modeling and simulation (in silico) within the regulatory process. This review article focuses on the approaches of in silico trials, the verification, validation, and uncertainty quantification involved in the regulatory evaluation of biomedical products that utilize predictive models.