How is the Pharmaceutical Industry Structured to Optimize Pediatric Drug Development? Existing Pediatric Structure Models and Proposed Recommendations for Structural Enhancement

Severin, Thomas; Corriol‐Rohou, Solange; Bucci‐Rechtweg, Christina; Haack, Kristina An; Fuerst‐Recktenwald, Sabine; Lepola, Pirkko; Norjavaara, Ensio; Dehlinger-Kremer, Martine; Haertter, Sebastian; Cheung, S.Y. Amy

doi:10.1007/s43441-020-00116-4

Cited by 8 publications

(7 citation statements)

References 12 publications

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“…Given the limited opportunities to collect data in children, modelling and simulation methodologies are being applied by academia, industry and regulatory agencies as powerful tools to optimize resources to design meaningful paediatric clinical studies for drug development 22,58–60 …”

Section: Discussionmentioning

confidence: 99%

Physiologically based pharmacokinetic modelling of semaglutide in children and adolescents with healthy and obese body weights

Machado,

Honorio,

Souza Domingos

et al. 2023

Brit J Clinical Pharma

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AimsTo develop paediatric physiologically based pharmacokinetic modelling (PBPK) models of semaglutide to estimate the pharmacokinetic profile for subcutaneous injections in children and adolescents with healthy and obese body weights.MethodsPharmacokinetic modelling and simulations of semaglutide subcutaneous injections were performed using the Transdermal Compartmental Absorption & Transit model implemented in GastroPlus v.9.5 modules. A PBPK model of semaglutide was developed and verified in the adult population, by comparing the simulated plasma exposure with the observed data, and further scaled to the paediatric populations with normal and obese body weight.ResultsThe semaglutide PBPK model was successfully developed in adults and scaled to the paediatric population. Our paediatric PBPK simulations indicated a significant increase in maximum plasma concentrations for the 10–14 years' paediatric population with healthy body weights, which was higher than the observed values in adults at the reference dose. Since gastrointestinal adverse events are related to increased semaglutide concentrations, peak concentrations outside the target range may represent a safety risk for this paediatric age group. Besides, paediatric PBPK models indicated that body weight was inversely related to semaglutide maximum plasma concentration, corroborating the consensus on the influence of body weight on semaglutide PK in adults.ConclusionPaediatric PBPK was successfully achieved using a top‐down approach and drug‐related parameters. The development of unprecedented PBPK models will support paediatric clinical therapy for applying aid‐safe dosing regimens for the paediatric population in diabetes treatment.

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Section: Discussionmentioning

confidence: 99%

Physiologically based pharmacokinetic modelling of semaglutide in children and adolescents with healthy and obese body weights

Machado,

Honorio,

Souza Domingos

et al. 2023

Brit J Clinical Pharma

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Section: Key Recommendations: Early Engagement Of Key Stakeholders and Patient Representatives And The Formation Of A Pediatric Expert Grmentioning

confidence: 99%

“…Several pharmaceutical companies have also established a Pediatric Expert Group (PEG) to better support the process of pediatric drug development [ 42 ]. As described by Severin et al, the structure as well as the roles and responsibilities of a PEG vary depending on the company [ 42 ]. Some PEGs have limited involvement with the pediatric drug development program, serving only as consultants, whereas other PEGs have ownership of and responsibility for the program [ 42 ].…”

Section: Key Recommendations: Early Engagement Of Key Stakeholders and Patient Representatives And The Formation Of A Pediatric Expert Grmentioning

confidence: 99%

“…As described by Severin et al, the structure as well as the roles and responsibilities of a PEG vary depending on the company [ 42 ]. Some PEGs have limited involvement with the pediatric drug development program, serving only as consultants, whereas other PEGs have ownership of and responsibility for the program [ 42 ]. Common to all PEG structures is an emphasis on medical functions, with expert pediatricians usually appointed to the group.…”

Section: Key Recommendations: Early Engagement Of Key Stakeholders and Patient Representatives And The Formation Of A Pediatric Expert Grmentioning

confidence: 99%

“…Common to all PEG structures is an emphasis on medical functions, with expert pediatricians usually appointed to the group. Representatives with expertise in preclinical/translational, regulations, clinical operations, and clinical pharmacology/pharmacometrics are also commonly appointed to PEGs [ 42 ]. Irrespective of how they are implemented, PEGs constitute a valuable resource for sponsors pursuing pediatric drug development.…”

Section: Key Recommendations: Early Engagement Of Key Stakeholders and Patient Representatives And The Formation Of A Pediatric Expert Grmentioning

confidence: 99%

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Navigating the Regulatory Landscape to Develop Pediatric Oncology Drugs: Expert Opinion Recommendations

et al. 2021

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Regulatory changes have been enacted in the United States (US) and European Union (EU) to encourage the development of new treatments for pediatric cancer. Here, we review some of the factors that have hampered the development of pediatric cancer treatments and provide a comparison of the US and EU regulations implemented to address this clinical need. We then provide some recommendations for each stage of the oncology drug development pathway to help researchers maximize their chance of successful drug development while complying with regulations. A key recommendation is the engagement of key stakeholders such as regulatory authorities, pediatric oncologists, academic researchers, patient advocacy groups, and a Pediatric Expert Group early in the drug development process. During drug target selection, sponsors are encouraged to consult the Food and Drug Administration (FDA), European Medicines Agency (EMA), and the FDA target list, in addition to relevant US and European consortia that have been established to characterize and prioritize oncology drug targets. Sponsors also need to carefully consider the resourcing requirements for preclinical testing, which include ensuring appropriate access to the most relevant databases, clinical samples, and preclinical models (cell lines and animal models). During clinical development, sponsors can account for the pharmacodynamic (PD)/pharmacokinetic (PK) considerations specific to a pediatric population by developing pediatric formulations, selecting suitable PD endpoints, and employing sparse PK sampling or modeling/simulation of drug exposures where appropriate. Additional clinical considerations include the specific design of the clinical trial, the potential inclusion of children in adult trials, and the value of cooperative group trials. Plain Language SummaryIn the last few decades, great progress has been made in developing new treatments for adult cancers. However, development of new treatments for childhood cancers has been much slower. To encourage drug companies (sponsors) to develop effective treatments for childhood cancer, authorities in the United States (US) and Europe have made new rules for drug development. Under these new rules, sponsors developing drugs for specific cancers in adults have to consider whether the target of that drug also causes cancers in children. If this is the case, sponsors have to carry out clinical studies of their drug in children who have cancer that is caused by the same drug target. In this article, we describe some reasons for why drug development for childhood cancers has been slow and the rules created to address this problem in the US and Europe. We share some recommendations to help sponsors maximize their chances of developing an effective drug in children while satisfying the new rules. Specifically, sponsors need to be aware of the differences between studying drugs in adults versus children and how these influence the way the drug is tested. We make several recommendations for each stage of the development process, b...

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Role of Clinical Pharmacology in Diversity and Inclusion in Global Drug Development: Current Practices and Industry Perspectives: White Paper

Sawant‐Basak,

Urva,

Mukker

et al. 2024

Clin Pharma and Therapeutics

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The 2022 United States Food and Drug Administration (US FDA) draft guidance on diversity plan (DP), which will be implemented through the Diversity Action Plans by December 2025, under the 21st Century Cures Act, marks a pivotal effort by the FDA to ensure that registrational studies adequately reflect the target patient populations based on diversity in demographics and baseline characteristics. This white paper represents the culminated efforts of the International Consortium of Quality and Innovation (IQ) Diversity and Inclusion (D&I) Working Group (WG) to assess the implementation of the draft FDA guidance by members of the IQ consortium in the discipline of clinical pharmacology (CP). This article describes current practices in the industry and emphasizes the tools and techniques of quantitative pharmacology that can be applied to support the inclusion of a diverse population during global drug development, to support diversity and inclusion of underrepresented patient populations, in multiregional clinical trials (MRCTs). It outlines strategic and technical recommendations to integrate demographics, including age, sex/gender, race/ethnicity, and comorbidities, in multiregional phase III registrational studies, through the application of quantitative pharmacology. Finally, this article discusses the challenges faced during global drug development, which may otherwise limit the enrollment of a broader, potentially diverse population in registrational trials. Based on the outcomes of the IQ survey that provided the current awareness of diversity planning, it is envisioned that in the future, industry efforts in the inclusion of previously underrepresented populations during global drug development will culminate in drug labels that apply to the intended patient populations at the time of new drug application or biologics license application rather than through post‐marketing requirements.

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How is the Pharmaceutical Industry Structured to Optimize Pediatric Drug Development? Existing Pediatric Structure Models and Proposed Recommendations for Structural Enhancement

Cited by 8 publications

References 12 publications

Physiologically based pharmacokinetic modelling of semaglutide in children and adolescents with healthy and obese body weights

Physiologically based pharmacokinetic modelling of semaglutide in children and adolescents with healthy and obese body weights

Navigating the Regulatory Landscape to Develop Pediatric Oncology Drugs: Expert Opinion Recommendations

Role of Clinical Pharmacology in Diversity and Inclusion in Global Drug Development: Current Practices and Industry Perspectives: White Paper

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