{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T02:30:36Z","timestamp":1794537036173,"version":"4.9.1"},"reference-count":28,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T00:00:00Z","timestamp":1620000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["79\/159\/2015\/NCD\u2010III"],"award-info":[{"award-number":["79\/159\/2015\/NCD\u2010III"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["2017\u201019"],"award-info":[{"award-number":["2017\u201019"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The biotherapeutic asparaginase is a cornerstone of therapy in acute lymphoblastic leukaemia (ALL). With limited access to the original native <jats:italic>Escherichia coli<\/jats:italic>\u2010derived asparaginase (EcASNase), a variety of EcASNase biogenerics are used in low\u2010middle\u2010income countries (LMICs). The variable quality of these biogenerics potentially influences clinical outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Seven biogeneric EcASNases (P1\u2013P7) marketed widely in India were evaluated, with P2 as an exemplar for in vivo monitoring. Therapeutic activity of P2 (10,000\u00a0IU\/m<jats:sup>2<\/jats:sup>\/dose, intramuscular, every 72\u00a0hours) was monitored during induction therapy, and drug\u2010related toxicities recorded. Molecular identity, purity and in vitro drug activity of seven biogenerics were characterised using multimodal analyses, and findings compared with reference EcASNase (R).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In patients (<jats:italic>N<\/jats:italic>\u00a0=\u00a062) receiving P2, subtherapeutic asparaginase activity (&lt;100\u00a0U\/L) was observed in 66% (46\/70) of trough timepoints (72\u00a0hours postdose) during induction. Twelve patients (19%), 11 with high\u2010risk ALL, developed hypersensitivity. Isoforms of EcASNase were identified in all seven biogenerics. All generic products contained impurities with batch\u2010to\u2010batch variability. These included high levels of protein aggregates and host cell protein contamination. In vitro assays of EcASNase activity and leukaemia cell line cytotoxicity were not discriminatory.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings confirm widespread concerns over the unsatisfactory quality and therapeutic activity of native EcASNase biogenerics marketed in LMICs. Appropriate use of these products requires monitored studies to identify clinical suitability and determine appropriate dosing and schedule. For large parts of the world, assured access to high\u2010quality asparaginases remains an unmet therapeutic need.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.29046","type":"journal-article","created":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T16:31:14Z","timestamp":1620059474000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Unsatisfactory quality of <i>E. coli<\/i> asparaginase biogenerics in India: Implications for clinical outcomes in acute lymphoblastic leukaemia"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5926-5167","authenticated-orcid":false,"given":"Jasmeet","family":"Sidhu","sequence":"first","affiliation":[{"name":"Department of Paediatric Haematology and Oncology Tata Medical Center  Kolkata India"},{"name":"Tata Translational Cancer Research Centre Tata Medical Center  Kolkata 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Translational Cancer Research Centre Tata Medical Center  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakriti","family":"Roy","sequence":"additional","affiliation":[{"name":"Tata Translational Cancer Research Centre Tata Medical Center  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogesh","family":"Phadke","sequence":"additional","affiliation":[{"name":"Gennova Vaccine Formulation and Research Centre  Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhatu","family":"Sonawane","sequence":"additional","affiliation":[{"name":"Gennova Vaccine Formulation and Research Centre  Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pritha","family":"Paul","sequence":"additional","affiliation":[{"name":"Tata Translational Cancer Research Centre Tata Medical Center  Kolkata India"},{"name":"Division of Cancer Sciences School of Medical Sciences Faculty of Biology, Medicine and Health, University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2916-9649","authenticated-orcid":false,"given":"Vaskar","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology and Oncology Tata Medical Center  Kolkata India"},{"name":"Tata Translational Cancer Research Centre Tata Medical Center  Kolkata India"},{"name":"Division of Cancer Sciences School of Medical Sciences Faculty of Biology, Medicine and Health, University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6769-3847","authenticated-orcid":false,"given":"Shekhar","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology and Oncology Tata Medical Center  Kolkata India"},{"name":"Tata Translational Cancer Research Centre Tata Medical Center  Kolkata India"},{"name":"Division of 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