(628g) Verification, Validation, and Uncertainty Quantification for Computational Modeling and Simulation in the Pharmaceutical Industry

Computational modeling and simulation (CM&S) is increasingly applied in the pharmaceutical industry to support various aspects of process development, manufacturing, and drug delivery. Applications range from scale-up of mixing processes to chromatography process development to autoinjector design, to name only a few. While traditionally used in early phase development activities, CM&S is now being adopted for activities that have higher business, operational, or even regulatory impact. This necessitates the need for establishing credibility of the digital evidence generated using CM&S.

The American Society of Mechanical Engineers (ASME) formed a standards committee focusing on verification, validation, and uncertainty quantification (VVUQ) for CM&S in 2000. The goal was to enable practitioners to establish confidence in CM&S results through the collection of credibility evidence through VVUQ. Already-published ASME standards provide consensus best practices for specific modeling disciplines, e.g., finite element analysis and computational fluid dynamics, and for a variety of applications, including aerospace, nuclear, and medical devices. Nevertheless, existing standards or guidelines supporting CM&S activities relevant to the pharmaceutical industry are either too general, e.g. ICH Points to Consider for ICH Q8/9/10, or are specific to other industries, e.g. the US FDA draft credibility guidance for medical devices submissions published in 2021. Therefore, the ASME sub-committee on VVUQ in Computational Modeling of Pharmaceutical Products was formed in March 2023 to address this gap. The charter of the sub-committee is to “provide procedures to standardize verification, validation, and uncertainty quantification in computational modeling of pharmaceutical process development, manufacturing, and drug delivery”. The goal of this subcommittee will be to leverage the existing ASME VVUQ standards and develop standards for simulations specific to the pharmaceutical industry.

This presentation will review case studies demonstrating the application of VVUQ principles to several pharmaceutical unit operations and will use these examples to illustrate the needs and future direction of this committee. Finally, we would like to extend a warm invitation for new members to join the committee. We seek to establish a vibrant team with a diverse range of interests in pharmaceutical operations so that we may provide the best possible impact for the industry.