{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:28:45Z","timestamp":1791484125142,"version":"4.3.4"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T00:00:00Z","timestamp":1669939200000},"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":[[2023,2]]},"abstract":"<jats:p>\n                    The US Food and Drug Administration (FDA) has taken steps to bring efficiency to the development of biosimilars, including establishing guidance for the use of pharmacokinetic and pharmacodynamic (PD) similarity study data without a comparative clinical study with efficacy end point(s). To better understand the potential role for PD biomarkers in biosimilar development and inform best practices for biomarker selection and analysis, we conducted a randomized, double\u2010blinded, placebo\u2010controlled, single\u2010dose, parallel\u2010arm clinical study in healthy participants. Eighty\u2010four healthy participants (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a012 per dose arm) received either placebo or one of three doses of either interferon \u03b2\u20101a (7.5\u201330\u2009\u03bcg) or pegylated interferon \u03b2\u20101a (31.25\u2013125\u2009\u03bcg) to evaluate the maximum change from baseline and the baseline\u2010adjusted area under the effect curve for the biomarkers neopterin in serum and myxovirus resistance protein 1 in blood. Both PD biomarkers increased following product administration with clear separation from baseline (neopterin: 3.4\u2010fold and 3.9\u2010fold increase for interferon \u03b2\u20101a and pegylated interferon \u03b2\u20101a, respectively; myxovirus resistance protein 1: 19.0\u2010fold and 47.2\u2010fold increase for interferon \u03b2\u20101a and pegylated interferon \u03b2\u20101a, respectively). The dose\u2013response curves support that therapeutic doses were adequately sensitive to detect differences in both PD biomarkers for consideration in a PD similarity study design. Because baseline levels of both biomarkers are low compared with on\u2010treatment values, there was little difference in using PD measures adjusted to baseline compared with the results without baseline adjustment. This study illustrates potential methodologies for evaluating PD biomarkers and an approach to address information gaps when limited information is publicly available for one or more PD biomarkers.\n                  <\/jats:p>","DOI":"10.1002\/cpt.2784","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T00:52:46Z","timestamp":1667436766000},"page":"339-348","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Considerations for Use of Pharmacodynamic Biomarkers to Support Biosimilar Development \u2013 (\n                    <scp>III<\/scp>\n                    ) A Randomized Trial with Interferon Beta\u20101a Products"],"prefix":"10.1111","volume":"113","author":[{"given":"Jeffry","family":"Florian","sequence":"first","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Gershuny","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Sun","sequence":"additional","affiliation":[{"name":"Therapeutic Biologics Program, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Schrieber","sequence":"additional","affiliation":[{"name":"Office of Therapeutic Biologics and Biosimilars, Office of New Drugs, Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0333-5020","authenticated-orcid":false,"given":"Murali K.","family":"Matta","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8195-7909","authenticated-orcid":false,"given":"Anthony","family":"Hazel","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5043-5617","authenticated-orcid":false,"given":"Morasa","family":"Sheikhy","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Weaver","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula L.","family":"Hyland","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010Hui","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giri","family":"Vegesna","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"DePalma","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aanchal","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"},{"name":"Booz Allen Hamilton  McLean Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Prentice","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"},{"name":"Booz Allen Hamilton  McLean Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Sanabria","sequence":"additional","affiliation":[{"name":"Spaulding Clinical Research  West Bend Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0663-7358","authenticated-orcid":false,"given":"Yow\u2010Ming","family":"Wang","sequence":"additional","affiliation":[{"name":"Therapeutic Biologics Program, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3023-3297","authenticated-orcid":false,"given":"David G.","family":"Strauss","sequence":"additional","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,2]]},"reference":[{"key":"e_1_2_10_1_1","unstructured":"US Food and Drug Administration.Guidance for industry: scientific considerations in demonstrating biosimilarity to a reference product<https:\/\/www.fda.gov\/media\/82647\/download> (2015). 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