Landscape of regulatory quantitative systems pharmacology submissions to the U.S. Food and Drug Administration: An update report

Abstract The number of quantitative systems pharmacology (QSP) submissions to the U.S. Food and Drug Administration has continued to increase over the past decade. This report summarizes the landscape of QSP submissions as of December 2023. QSP was used to inform drug development across various ther...

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Main Authors: Jane P. F. Bai, Guansheng Liu, Miao Zhao, Jie Wang, Ye Xiong, Tien Truong, Justin C. Earp, Yuching Yang, Jiang Liu, Hao Zhu, Gilbert J. Burckart
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:CPT: Pharmacometrics & Systems Pharmacology
Online Access:https://doi.org/10.1002/psp4.13208
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author Jane P. F. Bai
Guansheng Liu
Miao Zhao
Jie Wang
Ye Xiong
Tien Truong
Justin C. Earp
Yuching Yang
Jiang Liu
Hao Zhu
Gilbert J. Burckart
author_facet Jane P. F. Bai
Guansheng Liu
Miao Zhao
Jie Wang
Ye Xiong
Tien Truong
Justin C. Earp
Yuching Yang
Jiang Liu
Hao Zhu
Gilbert J. Burckart
author_sort Jane P. F. Bai
collection DOAJ
description Abstract The number of quantitative systems pharmacology (QSP) submissions to the U.S. Food and Drug Administration has continued to increase over the past decade. This report summarizes the landscape of QSP submissions as of December 2023. QSP was used to inform drug development across various therapeutic areas and throughout the drug development process of small molecular drugs and biologics and has facilitated dose finding, dose ranging, and dose optimization studies. Though the majority of QSP submissions (>66%) focused on drug effectiveness, QSP was also utilized to simulate drug safety including liver toxicity, risk of cytokine release syndrome (CRS), bone density, and others. This report also includes individual contexts of use from a handful of new drug applications (NDAs) and biologics license applications where QSP modeling was used to demonstrate the utility of QSP modeling in regulatory drug development. According to the models submitted in QSP submissions, an anonymous case was utilized to illustrate how QSP informed development of a bispecific monoclonal antibody with respect to CRS risk. QSP submissions for informing pediatric drug development were summarized along with highlights of a case in inborn errors of metabolism. Furthermore, simulations of response variability with QSP were described. In summary, QSP continues to play a role in informing drug development.
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spelling doaj-art-a7e647a5da584cbab6f6b190902bb27c2024-12-16T05:57:55ZengWileyCPT: Pharmacometrics & Systems Pharmacology2163-83062024-12-0113122102211010.1002/psp4.13208Landscape of regulatory quantitative systems pharmacology submissions to the U.S. Food and Drug Administration: An update reportJane P. F. Bai0Guansheng Liu1Miao Zhao2Jie Wang3Ye Xiong4Tien Truong5Justin C. Earp6Yuching Yang7Jiang Liu8Hao Zhu9Gilbert J. Burckart10Office of Clinical Pharmacology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USAOffice of Clinical Pharmacology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USAOffice of Clinical Pharmacology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USAOffice of Clinical Pharmacology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USAOffice of Clinical Pharmacology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USAOffice of Clinical Pharmacology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USAOffice of Clinical Pharmacology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USAOffice of Clinical Pharmacology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USAOffice of Clinical Pharmacology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USAOffice of Clinical Pharmacology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USAOffice of Clinical Pharmacology Center for Drug Evaluation and Research, U.S. Food and Drug Administration Silver Spring Maryland USAAbstract The number of quantitative systems pharmacology (QSP) submissions to the U.S. Food and Drug Administration has continued to increase over the past decade. This report summarizes the landscape of QSP submissions as of December 2023. QSP was used to inform drug development across various therapeutic areas and throughout the drug development process of small molecular drugs and biologics and has facilitated dose finding, dose ranging, and dose optimization studies. Though the majority of QSP submissions (>66%) focused on drug effectiveness, QSP was also utilized to simulate drug safety including liver toxicity, risk of cytokine release syndrome (CRS), bone density, and others. This report also includes individual contexts of use from a handful of new drug applications (NDAs) and biologics license applications where QSP modeling was used to demonstrate the utility of QSP modeling in regulatory drug development. According to the models submitted in QSP submissions, an anonymous case was utilized to illustrate how QSP informed development of a bispecific monoclonal antibody with respect to CRS risk. QSP submissions for informing pediatric drug development were summarized along with highlights of a case in inborn errors of metabolism. Furthermore, simulations of response variability with QSP were described. In summary, QSP continues to play a role in informing drug development.https://doi.org/10.1002/psp4.13208
spellingShingle Jane P. F. Bai
Guansheng Liu
Miao Zhao
Jie Wang
Ye Xiong
Tien Truong
Justin C. Earp
Yuching Yang
Jiang Liu
Hao Zhu
Gilbert J. Burckart
Landscape of regulatory quantitative systems pharmacology submissions to the U.S. Food and Drug Administration: An update report
CPT: Pharmacometrics & Systems Pharmacology
title Landscape of regulatory quantitative systems pharmacology submissions to the U.S. Food and Drug Administration: An update report
title_full Landscape of regulatory quantitative systems pharmacology submissions to the U.S. Food and Drug Administration: An update report
title_fullStr Landscape of regulatory quantitative systems pharmacology submissions to the U.S. Food and Drug Administration: An update report
title_full_unstemmed Landscape of regulatory quantitative systems pharmacology submissions to the U.S. Food and Drug Administration: An update report
title_short Landscape of regulatory quantitative systems pharmacology submissions to the U.S. Food and Drug Administration: An update report
title_sort landscape of regulatory quantitative systems pharmacology submissions to the u s food and drug administration an update report
url https://doi.org/10.1002/psp4.13208
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