{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T04:40:41Z","timestamp":1776660041332,"version":"3.51.2"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>We present here a repository of key regulatory questions answered in centralized procedures and evaluate the place of modeling and simulation in marketing authorization process for biologics approved for the treatment of moderate\u2010to\u2010severe asthma from 2014 to 2024. This was done consistently with the ICH M15 recommendations and the ERAMET project that consistently aim to define the framework for assessment of model informed drug development evidence to inform decision\u2010making. We carried out a search for marketing authorization applications for the five approved monoclonal antibodies in the treatment of asthma from 2014 to 2024. We translated the information into essential regulatory questions and classified the questions based on the level of the questions and their granularity. Credibility activities were performed by applying the credibility framework of the ICH M15 guidelines to questions answered by modeling and simulation methods. A total of 190 questions were extracted including 74 questions related to efficacy, 86 to safety, and 30 questions related to pharmacokinetics. The proportion of questions answered oscillated between 51% and 65% for each drug. Modeling and simulation methods were used to answer 25% of the questions. These methods are predominantly used to address pharmacokinetics questions, with 60% of these questions answered in at least one marketing authorization application using these methods. Credibility matrices were fulfilled for questions answered by modeling and simulation methods. We identified the types and roles of modeling and simulation approaches used in the development of monoclonal antibodies for treat moderate\u2010to\u2010severe asthma approved from 2014 to 2024.<\/jats:p>","DOI":"10.1002\/psp4.70222","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T10:52:42Z","timestamp":1774349562000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Use of Modeling and Simulation to Inform the Development of Monoclonal Antibodies to Treat Moderate\u2010to\u2010Severe Asthma: A Retrospective Review of\n                    <scp>EMA<\/scp>\n                    Centralized Procedure From 2014 to 2024"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3123-5289","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Haguet","sequence":"first","affiliation":[{"name":"Unit\u00e9 de Recherche Pharmacologie et Toxicologie Clinique (URPC), Namur Research Institute for Life Sciences (NARILIS), University of Namur  Namur Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2107-1804","authenticated-orcid":false,"given":"Jean\u2010Michel","family":"Dogn\u00e9","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Recherche Pharmacologie et Toxicologie Clinique (URPC), Namur Research Institute for Life Sciences (NARILIS), University of Namur  Namur Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8276-8870","authenticated-orcid":false,"given":"Flora T","family":"Musuamba","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Recherche Pharmacologie et Toxicologie Clinique (URPC), Namur Research Institute for Life Sciences (NARILIS), University of Namur  Namur Belgium"},{"name":"Federal Agency for Medicines and Health Products (FAMHP)  Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.921967"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3345\/cep.2025.00423"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2024.12.004"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00588\u20102019"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2018.11.007"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1478"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2143"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics2040364"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.04.00015404"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/ped.15595"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbx055"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2856"},{"key":"e_1_2_9_14_1","unstructured":"American Society of Mechanical Engineers \u201cAssessing Credibility of Computational Modeling through Verification and Validation: Application to Medical Devices ASME V&V 40\u20102018 \u201dASME New York NY 2018."},{"key":"e_1_2_9_15_1","doi-asserted-by":"crossref","unstructured":"L.Hanquet J.\u2010M.Dogn\u00e9 andF. T.Musuamba \u201cModelling and Simulation in Development and Regulatory Approval of Chimeric Antigen Receptor T\u2010Cell Therapies: An Analysis of European Medicines Agency Centralized Procedures From 2018 to 2024 \u201dManuscript Submitted for Publication 2025.","DOI":"10.1002\/psp4.70213"},{"key":"e_1_2_9_16_1","doi-asserted-by":"crossref","unstructured":"G. S.Govere J.\u2010M.Dogn\u00e9 andF. T.Musuamba \u201cAssessment and Benchmarking of Model Informed Approaches in Drug Development for Haemoglobinopathies\u2014A Review of Scientific Advices From January 2000 to December 2024 \u201dManuscript Submitted for Publication 2025.","DOI":"10.1002\/psp4.70192"},{"key":"e_1_2_9_17_1","unstructured":"A.Olama J.\u2010M.Dogn\u00e9 andF. T.Musuamba \u201cCredibility Assessment of Model Informed Drug Development in Pediatric Pain: A Review of Pediatric Investigation Plans From 2008 to 2024 \u201dManuscript In Preparation 2025."},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13020299"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01527"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12465"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12887"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010022\u201003288\u2010w"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1086551"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2022.2056944"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2815"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/antib13030054"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12842"},{"key":"e_1_2_9_28_1","unstructured":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) \u201cICH M15 Model Informed Drug Development (MIDD) Guideline \u201d2025."}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70222","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/psp4.70222","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T03:59:21Z","timestamp":1776657561000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.70222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,24]]},"references-count":27,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/psp4.70222"],"URL":"https:\/\/doi.org\/10.1002\/psp4.70222","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,24]]},"assertion":[{"value":"2025-08-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70222"}}