title: Physiologically based pharmacokinetic modeling in regulatory decision-making at the European Medicines Agency.
abstract: Physiologically based pharmacokinetic (PBPK) modeling is a valuable tool in drug development and regulatory assessment, as it offers the opportunity to simulate the pharmacokinetics of a compound, with a mechanistic understanding, in a variety of populations and situations. This work reviews the use and impact of such modeling in selected regulatory procedures submitted to the European Medicines Agency (EMA) before the end of 2015, together with its subsequent reflection in public documents relating to the assessment of these procedures. It is apparent that the reference to PBPK modeling in regulatory public documents underrepresents its use. A positive trend over time of the number of PBPK models submitted is shown, and in a number of cases the results of these may impact the decision-making process or lead to recommendations in the product labeling. These results confirm the need for regulatory guidance in this field, which is currently under development by the EMA.
authors: European Medicines Agency (EMA), London, UK.
authors: E
authors: E
authors: Luzon
authors: European Medicines Agency (EMA), London, UK.
authors: K
authors: K
authors: Blake
authors: Medicines and Healthcare products Regulatory Agency (MHRA), London, UK.|Pharmacokinetics Working Party (PKWP), EMA, London, UK.|Modelling and Simulation Working Group (MSWG), EMA, London, UK.
authors: S
authors: S
authors: Cole
authors: Modelling and Simulation Working Group (MSWG), EMA, London, UK.|Medical Products Agency (MPA), Uppsala, Sweden.
authors: A
authors: A
authors: Nordmark
authors: Pharmacokinetics Working Party (PKWP), EMA, London, UK.|Medicines Evaluation Board (MEB), Utrecht, Netherlands.
authors: C
authors: C
authors: Versantvoort
authors: Pharmacokinetics Working Party (PKWP), EMA, London, UK.|Medical Products Agency (MPA), Uppsala, Sweden.
authors: E Gil
authors: EG
authors: Berglund
mesh_terms: D000076722:Drug Development / Q000379:methods / Q000592:standards; D004335:Drug and Narcotic Control / Q000379:methods / Q000458:organization & administration; D005060:Europe; D006077:Government Agencies; D006801:Humans; D008954:Models, Biological; D020380:Needs Assessment; D010599:Pharmacokinetics; D010829:Physiological Phenomena / Q000187:drug effects; D011050:Policy Making