{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T15:34:42Z","timestamp":1766504082097,"version":"3.40.5"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T00:00:00Z","timestamp":1663545600000},"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":[[2023,4]]},"abstract":"<jats:p>There is over a hundred years of clinical experience with insulin for the treatment of diabetes. The US Food and Drug Administration (FDA) approved the first insulin biosimilar interchangeable product in 2021 for improving glycemic control in adults and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. Several recombinant insulin products are available in the United States, including the recently approved biosimilar insulins. The approval of the biosimilar insulin products was based on comparative analytical characterizations and comparative pharmacokinetic (PK) and pharmacodynamic (PD) data. The primary objective of this review is to discuss the scientific considerations in the demonstration of biosimilarity of a proposed insulin biosimilar to a reference product and the role of clinical pharmacology studies in the determination of biosimilarity and interchangeability. Euglycemic clamp studies are considered a \u201cgold standard\u201d for insulin PK and PD characterization and have been widely used to determine the time\u2010action profiles of rapid\u2010acting, intermediate\u2010acting, and long\u2010acting insulin products. Clinical pharmacology aspects of study design, including selection of appropriate dose, study population, PK, and PD end points, are presented. Finally, the role of clinical pharmacology studies in the interchangeability assessment of insulin and the regulatory pathways used for insulin and the experience with follow\u2010on insulins and the two recently approved biosimilar insulin products is discussed.<\/jats:p>","DOI":"10.1002\/cpt.2731","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T08:04:31Z","timestamp":1662105871000},"page":"794-802","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Leveraging Clinical Pharmacology Data to Assess Biosimilarity and Interchangeability of Insulin Products"],"prefix":"10.1111","volume":"113","author":[{"given":"Jayabharathi","family":"Vaidyanathan","sequence":"first","affiliation":[{"name":"1Office of Clinical Pharmacology, Office of Translational Sciences Center of Drug Evaluation and Research, US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0663-7358","authenticated-orcid":false,"given":"Yow\u2010Ming C.","family":"Wang","sequence":"additional","affiliation":[{"name":"1Office of Clinical Pharmacology, Office of Translational Sciences Center of Drug Evaluation and Research, US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1307-7616","authenticated-orcid":false,"given":"Doanh","family":"Tran","sequence":"additional","affiliation":[{"name":"1Office of Clinical Pharmacology, Office of Translational Sciences Center of Drug Evaluation and Research, US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shirley K.","family":"Seo","sequence":"additional","affiliation":[{"name":"1Office of Clinical Pharmacology, Office of Translational Sciences Center of Drug Evaluation and Research, US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,19]]},"reference":[{"key":"e_1_2_11_1_1","unstructured":"U.S. Food and Drug Administration.FDA approves first interchangeable biosimilar insulin product for treatment of diabetes(2021)."},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2012.03.002"},{"key":"e_1_2_11_3_1","unstructured":"U.S. Food and Drug Administration.Interpretation of the \"deemed to be a licence\" provision of the biologics price competition and innovation act of 2009. 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