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US FDA reviews physiologically-based pharmacokinetic modelling in regulatory submissions
Date: 04 Jan 2011
A new paper published in the journal Clinical Pharmacology and Therapeutics provides examples of how physiologically-based pharmacokinetic (PBPK) modelling and simulation is being used during regulatory review.
Between 2008 and 2010, the US Food and Drug Administration (FDA) received seven Investigational New Drug (IND) and six New Drug Application (NDA) submissions using PBPK modelling and simulation. In a further four NDA cases, where the sponsors had not used PBPK, the FDA reviewers conducted their own modelling and simulation to support the clinical pharmacology reviews. Those case studies are outlined in this article.
Most of the modelling and simulation evaluations related to drug-drug interactions. They provided information that helped sponsors assess the need for specific clinical pharmacology studies, specific study design and appropriate language for labelling. In addition, paediatric dosing, and the impact of hepatic impairment or other factors on drug exposure were investigated. The Simcyp Population-based Simulator was one of the platforms used in the sponsor submissions.
The study was carried out by Ping Zhao and colleagues in the Office of Clinical Pharmacology, Center for Drug Evaluation and Research at the US Food and Drug Administration (FDA). The authors discuss the challenges encountered and recommend approaches to fully utilise PBPK modelling and simulation in regulatory submissions. It was also noted that the use of PBPK has increased considerably over recent years – in the three years prior to this study period the FDA received only two submissions which were supported by PBPK modelling and simulation.
The paper is entitled ‘Applications of physiologically-based pharmacokinetic (PBPK) modelling and simulation during regulatory review’. The abstract and full text options for the paper can be found here.