In-depth analysis of patterns in selection of different physiologically-based pharmacokinetic modeling tools: Part II - Assessment of model reusability and comparison between open and non-open source-code software

Whilst the reproducibility of models in the area of systems biology and quantitative systems pharmacology has been the focus of attention lately, the concept of 'reusability' is not addressed. With the advent of the 'Model Master File' dominating some regulatory discussions on pharmaceutical applications of physiologically-based pharmacokinetic (PBPK) models, reusability becomes a vital aspect of confidence in their use. Herein, we define 'reusability' specifically in the context of PBPK models and investigate the influence of open versus non-open source-code (NOSC) nature of the software on the extent of 'reusability'. Original articles (n = 145) that were associated with the development of novel PBPK models were identified as source models and citations to these reports, which involved further PBPK model development, were explored (n > 1800) for reuse cases of the source PBPK model whether in full or partial form. The nature of source-code was a major determinant of external reusability for PBPK models (>50% of the NOSC models as opposed <25% of open source-code [OSC]). Full reusability of the models was not common and mostly involved internal reuse of the OSC model (by the group who had previously developed the original model). The results were stratified by the software utilised (various), organisations involved (academia, industry, regulatory), and type of reusability (full vs. partial). The clear link between external reuse of models and NOSC PBPK software might stem from many elements related to quality and trust that require further investigation, and challenges the unfounded notion that OSC models are associated with higher uptake for reuse.

Automated summary

While the reproducibility of models in systems biology and quantitative systems pharmacology has received recent attention, the concept of 'reusability' has been neglected. This study defines 'reusability' in the context of physiologically-based pharmacokinetic (PBPK) models and examines the impact of open source-code versus non-open source-code (NOSC) software on the extent of reusability. The results show that the nature of the source-code significantly influences the external reusability of PBPK models, with NOSC models being more reusable compared to open source-code (OSC) models.