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Investigating the state of physiologically based kinetic modelling practices and challenges associated with gaining regulatory acceptance of model applications
Citation:
Paini, A., J. Leonard, T. Kliment, C. Tan, AND A. Worth. Investigating the state of physiologically based kinetic modelling practices and challenges associated with gaining regulatory acceptance of model applications. REGULATORY TOXICOLOGY AND PHARMACOLOGY. Elsevier Science Ltd, New York, NY, 90:104-115, (2017).
Impact/Purpose:
The objective of this article is to outline and report the results from this survey to provide insight into the current applications of PBK models in research and regulatory communities, as well as challenges in regards to applying and evaluating PBK models that are constructed using data generated by NAMs. The survey findings and our analyses of the results provide valuable information on current practices in model development, application, and evaluation using a variety of modelling platforms. This information will be used to identify the key elements that should be included in the updated guidance on GMP for PBK models designed to support regulatory risk assessment applications.
Description:
Physiologically based kinetic (PBK) models are used widely throughout a number of working sectors, including academia and industry, to provide insight into the dosimetry related to observed adverse health effects in humans and other species. Use of these models has increased over the last several decades, especially in conjunction with emerging alternative methods to animal testing, such as in vitro studies and data-driven in silico quantitative-structure-activity-relationship (QSAR) predictions. Experimental information derived from these new approach methods can be used as input for model parameters and allows for increased confidence in models for chemicals that did not have in vivo data for model calibration. Despite significant advancements in good modelling practice (GMP) for model development and evaluation, there remains some reluctance among regulatory agencies to use such models during the risk assessment process. Here, the results of a survey disseminated to the modelling community are presented in order to inform the frequency of use and applications of PBK models in science and regulatory submission. Additionally, the survey was designed to identify a network of investigators involved in PBK modelling and knowledgeable of GMP so that they might be contacted in the future for peer review of PBK models, especially in regards to vetting the models to such a degree as to gain a greater acceptance for regulatory purposes.
