{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:11:32Z","timestamp":1787238692335,"version":"build-2736575974"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:00:00Z","timestamp":1661299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>This study applied modeling and simulation (M&amp;S) approaches to evaluate the sensitivity of pegfilgrastim pharmacokinetics (PKs) and pharmacodynamics (PDs) to changes in dose amount, and linear or nonlinear clearance (CL) over pegfilgrastim subcutaneous dose of 2\u20136\u2009mg. A previously published model was adapted to better describe pegfilgrastim PK and PD data in healthy subjects and used in simulation. Nonlinear CL accounts for 98% and 77%, respectively, of the total CL of pegfilgrastim at 2 and 6\u2009mg. The sensitivity analyses showed: (i) PK of 2 and 6\u2009mg doses are similarly sensitive to detect differences for a 5% change in dose; (ii) PK of 2\u2009mg dose is more sensitive to changes in receptor binding affinity, a model parameter for nonlinear CL, and a product quality attribute characterized with orthogonal methods as part of demonstrating analytical similarity between products; (iii) PK of approved 6\u2009mg dose is more sensitive to changes in linear CL, which has not been associated with any specific product quality attributes, and (iv) the PDs are not sensitive to changes in linear or nonlinear CL. Taken together, our analyses support that the approved pegfilgrastim dose of 6\u2009mg is appropriate for detecting differences between a biosimilar and the reference products in pegfilgrastim PK and PD similarity studies. The described M&amp;S approaches can be adopted to support dose selection for biosimilars with nonlinear PK and complex PK\u2013PD interplay.<\/jats:p>","DOI":"10.1002\/cpt.2722","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T12:26:15Z","timestamp":1659097575000},"page":"62-70","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Model\u2010Based Approach to Selecting Pegfilgrastim Dose for Pharmacokinetic and Pharmacodynamic Similarity Studies in Biosimilar Development"],"prefix":"10.1111","volume":"113","author":[{"given":"Fang","family":"Li","sequence":"first","affiliation":[{"name":"Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland 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