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Physiologically Based Pharmacokinetics Is Impacting Drug Development and Regulatory Decision Making
M Rowland1, L J Lesko2, A Rostami-Hodjegan3
1Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, University of Manchester Manchester, UK ; Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and Medicine, University of California San Francisco, California, USA.
CPT: Pharmacometrics & Systems Pharmacology
|July 31, 2015
Summary
Physiologically based pharmacokinetic (PBPK) modeling is transitioning to an industrial standard in drug development. Regulatory agencies are encouraging PBPK use to enhance drug development and decision-making processes.
Area of Science:
- Pharmacokinetics and Drug Development
Background:
- Physiologically based pharmacokinetic (PBPK) modeling is shifting from academic research to widespread industrial application.
- Regulatory bodies like the FDA and MHRA are increasingly encouraging the use of PBPK models in drug development.
- Recent publications highlight the growing importance and regulatory acceptance of PBPK in clinical settings.
Purpose of the Study:
- To discuss the impact and best practices of PBPK modeling in clinical drug development.
- To facilitate the development of regulatory guidances for PBPK applications within model-informed drug development.
- To explore how PBPK can inform regulatory decision-making.
Main Methods:
- Analysis of reports from FDA and MHRA meetings on PBPK applications.
- Review of European Medicines Agency's Concept Paper on PBPK.
- Comparison with historical regulatory acceptance of population PK/PD and nonlinear mixed effects modeling.
Main Results:
- PBPK modeling is recognized as a valuable tool complementing or replacing traditional modeling approaches.
- PBPK models provide mechanistic insights into absorption, distribution, metabolism, and excretion (ADME) processes.
- Understanding physiological drivers and their interaction with drug factors is crucial for predicting drug behavior.
Conclusions:
- PBPK modeling represents a significant advancement in understanding drug behavior.
- Regulatory agencies are actively supporting the integration of PBPK into drug development.
- PBPK facilitates more informed regulatory decisions and enhances drug development strategies.
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