{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:18:30Z","timestamp":1790713110034,"version":"4.1.0"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T00:00:00Z","timestamp":1761436800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T00:00:00Z","timestamp":1761436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ther Innov Regul Sci"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The Biomarker Qualification Program (BQP), formally established in 2016 under the\n                      <jats:italic>21st Century Cures Act<\/jats:italic>\n                      , is a key pathway for developing novel biomarkers for regulatory use. We evaluated eight\u00a0years of BQP experience to assess whether it has facilitated the qualification of novel biomarkers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We collected characteristics and submission dates for accepted biomarker qualification projects from the FDA\u2019s Drug Development Tool Qualification Project Search database.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      As of July 1, 2025, 61 projects were accepted into the BQP. Safety (30%), Diagnostic (21%), and PD Response (20%) biomarkers were the most common. Projects primarily used molecular (46%) and radiologic\/imaging (39%) methods and were split between measures of a disease\/condition or drug response\/effect of exposure. Few projects included surrogate endpoint biomarkers (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095). Half of the accepted projects remained at the initial Letter of Intent (LOI) stage, and only eight biomarkers were qualified through the program. LOI and Qualification Plan (QP) reviews frequently exceeded FDA targets by three\u00a0months and seven\u00a0months, respectively. For projects reaching the QP stage, QP development took a median of 32\u00a0months, with surrogate endpoints taking 47\u00a0months.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The BQP supports the development of certain biomarkers but has seen limited use for biomarkers intended as surrogate endpoints. Coupled with longer timelines for their QP development, these trends demonstrate the program may not be well-suited for advancing novel response biomarkers. Given significant stakeholder interest in novel surrogate measures, a dedicated program may better support novel response biomarker development, particularly for biomarkers with applicability across multiple drug development programs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s43441-025-00889-6","type":"journal-article","created":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T18:48:49Z","timestamp":1761504529000},"page":"302-308","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hurry Up and Wait: Timelines and Takeaways from the Biomarker Qualification Program"],"prefix":"10.1007","volume":"60","author":[{"given":"Grace","family":"Collins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff D.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hillary S.","family":"Andrews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernat","family":"Navarro-Serer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,26]]},"reference":[{"issue":"1","key":"889_CR1","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1002\/cpt.136","volume":"98","author":"S Amur","year":"2015","unstructured":"Amur S, LaVange L, Zineh I, Buckman-Garner S, Woodcock J. Biomarker qualification: toward a multiple stakeholder framework for biomarker development, regulatory acceptance, and utilization. Clin Pharmacol Ther. 2015;98(1):34\u201346. https:\/\/doi.org\/10.1002\/cpt.136.","journal-title":"Clin Pharmacol Ther"},{"issue":"2","key":"889_CR2","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1002\/cpt.264","volume":"99","author":"G Lavezzari","year":"2016","unstructured":"Lavezzari G, Womack A. Industry perspectives on biomarker qualification. Clin Pharmacol Ther. 2016;99(2):208\u201313. https:\/\/doi.org\/10.1002\/cpt.264.","journal-title":"Clin Pharmacol Ther"},{"key":"889_CR3","unstructured":"U.S. Food and Drug Administration. Drug Development Tool (DDT) Qualification Programs: Biomarker Qualification Program. Accessed June 30, 2025. https:\/\/www.fda.gov\/drugs\/drug-development-tool-ddt-qualification-programs\/biomarker-qualification-program"},{"issue":"1","key":"889_CR4","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1002\/cpt.3661","volume":"118","author":"M Shahzad","year":"2025","unstructured":"Shahzad M, Stern AD. Participants in the FDA\u2019s biomarker qualification program. Clin Pharmacol Ther. 2025;118(1):80\u20134. https:\/\/doi.org\/10.1002\/cpt.3661.","journal-title":"Clin Pharmacol Ther"},{"issue":"4","key":"889_CR5","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1007\/s43441-025-00790-2","volume":"59","author":"F Yang","year":"2025","unstructured":"Yang F, Bousnina I, Madej A, Kalamegham R. Has FDA\u2019s drug development tools qualification program improved drug development? Ther Innov Regul Sci. 2025;59(4):871\u201381. https:\/\/doi.org\/10.1007\/s43441-025-00790-2.","journal-title":"Ther Innov Regul Sci"},{"key":"889_CR6","unstructured":"U.S. Food and Drug Administration. CDER & CBER Drug Development Tool Qualification Project Search. Accessed July 1, 2025. https:\/\/force-dsc.my.site.com\/ddt\/s\/"},{"key":"889_CR7","unstructured":"U.S. Food and Drug Administration. Guidance for Industry and FDA Staff: Qualification Process for Drug Development Tools. Published online November 2020. Accessed June 1, 2025. https:\/\/www.fda.gov\/media\/133511\/download"},{"key":"889_CR8","unstructured":"U.S. Food and Drug Administration. Rare Disease Endpoint Advancement (RDEA) Pilot Program. January 3, 2024. Accessed July 15, 2025. https:\/\/www.fda.gov\/drugs\/development-resources\/rare-disease-endpoint-advancement-pilot-program#Goals%20of%20the%20RDEA%20Pilot%20Program"},{"key":"889_CR9","unstructured":"U.S. Food and Drug Administration. Guidance for Industry: Hematologic Malignancies: Regulatory Considerations for Use of Minimal Residual Disease in Development of Drug and Biological Products for Treatment. Published online January 2020. Accessed July 31, 2025. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/hematologic-malignancies-regulatory-considerations-use-minimal-residual-disease-development-drug-and"},{"key":"889_CR10","unstructured":"U.S. Food and Drug Administration. Guidance for Industry: Pathological Complete Response in Neoadjuvant Treatment of High-Risk Early-Stage Breast Cancer: Use as an Endpoint to Support Accelerated Approval. Published online July 2020. Accessed July 31, 2025. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/pathological-complete-response-neoadjuvant-treatment-high-risk-early-stage-breast-cancer-use"},{"key":"889_CR11","unstructured":"U.S. Food and Drug Administration. Guidance for Industry: Use of Circulating Tumor Deoxyribonucleic Acid for Early-Stage Solid Tumor Drug Development. Published online November 2024. Accessed July 31, 2025. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/use-circulating-tumor-deoxyribonucleic-acid-early-stage-solid-tumor-drug-development-guidance"},{"issue":"9938","key":"889_CR12","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/S0140-6736(13)62422-8","volume":"384","author":"P Cortazar","year":"2014","unstructured":"Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164\u201372. https:\/\/doi.org\/10.1016\/S0140-6736(13)62422-8.","journal-title":"Lancet"},{"key":"889_CR13","unstructured":"Circulating Tumor DNA in Development of Therapies for Cancer: An Evidentiary Roadmap to an Early Endpoint for Regulatory Decision-Making. Published online July 2022. Accessed July 24, 2025. https:\/\/friendsofcancerresearch.org\/wp-content\/uploads\/Circulating_Tumor_DNA_in_Development_of_Therapies_for_Cancer-Evidentiary_Roadmap.pdf"},{"issue":"4","key":"889_CR14","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1182\/blood.2024024371","volume":"144","author":"O Landgren","year":"2024","unstructured":"Landgren O, Prior TJ, Masterson T, et al. EVIDENCE meta-analysis: evaluating minimal residual disease as an intermediate clinical end point for multiple myeloma. Blood. 2024;144(4):359\u201367. https:\/\/doi.org\/10.1182\/blood.2024024371.","journal-title":"Blood"},{"key":"889_CR15","unstructured":"Exploring the Use of Circulating Tumor DNA As A Monitoring Tool for Drug Development. Published online November 2018. Accessed July 24, 2025. https:\/\/friendsofcancerresearch.org\/wp-content\/uploads\/Circulating-Tumor-DNA.pdf"}],"container-title":["Therapeutic Innovation &amp; Regulatory Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-025-00889-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43441-025-00889-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-025-00889-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T03:04:19Z","timestamp":1767150259000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43441-025-00889-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,26]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["889"],"URL":"https:\/\/doi.org\/10.1007\/s43441-025-00889-6","relation":{},"ISSN":["2168-4790","2168-4804"],"issn-type":[{"value":"2168-4790","type":"print"},{"value":"2168-4804","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,26]]},"assertion":[{"value":"1 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}