title: Utilisation of pharmacokinetic-pharmacodynamic modelling and simulation in regulatory decision-making.
abstract: Modelling and simulation (M&S) play an important role in regulatory decision-making that affects both the public and industry. Technological advances in various fields related to drug development call for more focus on ways to optimise current drug development practices. Recognition of the potential of M&S by regulatory agencies inevitably has a substantial impact on drug development. The objective of the current review is to present the various regulatory initiatives for application of M&S to clinical drug development. The relevant parts of the various recommendations issued by the US Food and Drug Administration (FDA), via guidance documents and advisory committee meeting proceedings, are highlighted. Application of M&S to a variety of activities, such as integrating pharmacokinetic-pharmacodynamic knowledge across a new drug application and designing efficient trials, is discussed. Some of the challenges that pharmaceutical institutions currently face when implementing M&S projects, such as team structure, communication with regulators, training and time constraints, are also presented, and solutions are proposed.
authors.affiliation: Division of Pharmacometrics, United States Food and Drug Administration, Office of Clinical Pharmacology and Biopharmaceutics, Center for Drug Evaluation and Research, Rockville, Maryland 20852, USA. gobburuj@cder.fda.gov
authors.forename: J V
authors.initials: JV
authors.lastname: Gobburu
authors.forename: P J
authors.initials: PJ
authors.lastname: Marroum
mesh_terms: D000328:Adult; D002648:Child; D003657:Decision Making; D017277:Drug Approval / Q000379:methods / Q000458:organization & administration; D006801:Humans; D008954:Models, Biological; D010599:Pharmacokinetics; D010600:Pharmacology; D014481:United States; D014486:United States Food and Drug Administration