Developmental pharmacology describes the impact of maturation on drug disposition (pharmacokinetics, PK) and drug effects (pharmacodynamics, PD) throughout the paediatric age range. This paper, written by a multidisciplinary group of experts, summarizes current knowledge, and provides suggestions to pharmaceutical companies, regulatory agencies and academicians on how to incorporate the latest knowledge regarding developmental pharmacology and innovative techniques into neonatal and paediatric drug development. Biological aspects of drug absorption, distribution, metabolism and excretion throughout development are summarized. Although this area made enormous progress during the last two decades, remaining knowledge gaps were identified. Minimal risk and burden designs allow for optimally informative but minimally invasive PK sampling, while concomitant profiling of drug metabolites may provide additional insight in the unique PK behaviour in children. Furthermore, developmental PD needs to be considered during drug development, which is illustrated by disease- and/or target organ-specific examples. Identifying and testing PD targets and effects in special populations, and application of age- and/or population-specific assessment tools are discussed. Drug development plans also need to incorporate innovative techniques such as preclinical models to study therapeutic strategies, and shift from sequential enrolment of subgroups, to more rational designs. To stimulate appropriate research plans, illustrations of specific PK/PD-related as well as drug safety-related challenges during drug development are provided. The suggestions made in this joint paper of the Innovative Medicines Initiative conect4children Expert group on Developmental Pharmacology and the European Society for Developmental, Perinatal and Paediatric Pharmacology, should facilitate all those involved in drug development.

Biozentrum University of Basel Basel Switzerland

Clinical Research Centre The 1st Affiliated Hospital of Shandong 1st Medical University and Shandong Provincial Qianfoshan Hospital Jinan China

Department of Clinical Pharmacy Key Laboratory of Chemical Biology School of Pharmaceutical Sciences Cheeloo College of Medicine Shandong University China

Department of Development and Regeneration KU Leuven Leuven Belgium

Department of Hospital Pharmacy Erasmus MC University Medical Center Rotterdam the Netherlands

Department of Orthopedics and Traumatology Medical University of Graz Graz Austria

Department of Paediatrics and Inherited Metabolic Disorders 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Department of Pediatric Intensive Care Ghent University Hospital Ghent Belgium

Department of Pediatric Nephrology Radboud University Medical Center Radboud Institute for Molecular Life Sciences Amalia Children's Hospital Nijmegen the Netherlands

Department of Pharmaceutical and Pharmacological Sciences KU Leuven Leuven Belgium

Department of Pharmacology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Department of Pharmacology and Toxicology Radboud Institute Health Sciences Radboud University Medical Center Nijmegen the Netherlands

Department of Pharmacy Ghent University Hospital Ghent Belgium

Department of Pharmacy The 1st Affiliated Hospital of Shandong 1st Medical University and Shandong Provincial Qianfoshan Hospital Jinan China

Department of Physiology and Pharmacology Karolinska Institutet and Karolinska University Hospital Stockholm Sweden

Department of Women's and Children's Health Institute of Life Course and Medical Sciences University of Liverpool Liverpool Health Partners Liverpool UK

Division of Child and Adolescent Neuropsychiatry Department of Public Health and Pediatrics University of Torino Torino Italy

Division of Clinical Pharmacology Children's National Hospital Washington DC USA

Drug Delivery and Disposition Department of Pharmaceutical and Pharmacological Sciences KU Leuven Leuven Belgium

Great Ormond Street Hospital for Children NHS Foundation Trust London UK

Heymans Institute of Pharmacology Ghent University Ghent Belgium

Institute for Infection and Immunity St George's University of London London UK

Institute for Inherited Metabolic Diseases and Department of Pediatrics Paracelsus Medical University Clinical Research Center Salzburg Salzburg Austria

Institute of Psychiatry and Mental Health Child and Adolescent Psychiatry Department Hospital General Universitario Gregorio Marañón School of Medicine Universidad Complutense IiSGM CIBERSAM Madrid Spain

Intensive Care and Pediatric Surgery Erasmus MC Sophia Children's Hospital Rotterdam the Netherlands

Neonatal intensive care unit Fondazione IRCCS Ca' Grande Ospedale Maggiore Policlinico Milan Italy

Neonatal intensive Care unit University Hospitals Leuven Leuven Belgium

Paediatric Pharmacology and Pharmacometrics University Children's Hospital Basel University of Basel Basel Switzerland

Pediatric Clinical Research Center Queen Silvia Children's Hospital Sahlgrenska University Hospital Gothenburg Sweden

UCL Great Ormond Street Institute of Child Health London UK

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