{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:02Z","timestamp":1787013902714,"version":"build-2736575974"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T00:00:00Z","timestamp":1581984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>L\u2010asparaginase is an essential medicine in the treatment of pediatric acute lymphoblastic leukemia (ALL) and the quality of generic formulations is an area of concern. We compared nine generic formulations of L\u2010asparaginase available in India with the innovator.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The quality of formulations was assessed by measuring 72\u2010hour trough asparaginase activity in children with ALL during induction following administration of 10,000 IU\/m\n                      <jats:sup>2<\/jats:sup>\n                      of L\u2010asparaginase.\n                      <jats:italic>In\u2010vitro<\/jats:italic>\n                      analysis of the label claim was assessed by measuring activity of three generic formulations. Liquid chromatography\u2010mass spectrometry (LC\/MS) was used to determine the amount of host contaminant proteins (HCPs) in the formulations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Between March 2015 to June 2018, 240 samples from 195 patients were analyzed. The number of samples analyzed ranged from 7\u201366 per generic brand (median: 18) and seven of the innovator. The proportion of generic formulations that failed to achieve a predefined clinical threshold activity of 50 IU\/L ranged from 16.7% (2\/12) to 84.9% (28\/33) in the highest activity to lowest activity generic respectively. On other hand, all innovator samples had activity greater than 50 IU\/L.\n                      <jats:italic>In\u2010vitro<\/jats:italic>\n                      asparaginase activity in the three generic formulations tested ranged from 71.4\u201374.6% of the label claim (10,000 IU) compared to 93.5% for the innovator. LC\/MS analysis of generic 5 identified 25 HCPs with a relative peptide count of 27.1% of the total peptides.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Generic formulations had lower asparaginase activity which raises serious clinical concerns regarding their quality. Until stringent regulatory enforcement improves the quality of these generics, dose adaptive strategies coupled with therapeutic drug monitoring need to be considered.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.14216","type":"journal-article","created":{"date-parts":[[2020,1,11]],"date-time":"2020-01-11T03:23:47Z","timestamp":1578713027000},"page":"1081-1088","source":"Crossref","is-referenced-by-count":38,"title":["A comparison of asparaginase activity in generic formulations of\n                    <i>E.coli<\/i>\n                    derived L\u2010 asparaginase: In\u2010vitro study and retrospective analysis of asparaginase monitoring in pediatric patients with leukemia"],"prefix":"10.1111","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0666-2630","authenticated-orcid":false,"given":"Hari","family":"Sankaran","sequence":"first","affiliation":[{"name":"Department of Paediatric Oncology Tata Memorial Hospital  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumika","family":"Sengupta","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology ACTREC, Tata Memorial Centre  Navi Mumbai India"},{"name":"KIIT School of Biotechnology KIIT Deemed to be University  Bhubaneswar Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaitashi","family":"Purohit","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology ACTREC, Tata Memorial Centre  Navi Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand","family":"Kotagere","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology Tata Memorial Hospital  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirmalya Roy","family":"Moulik","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology Tata Memorial Hospital  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Prasad","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology Tata Memorial Hospital  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chetan","family":"Dhamne","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology Tata Memorial Hospital  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurav","family":"Narula","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology Tata Memorial Hospital  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shripad","family":"Banavali","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology Tata Memorial Hospital  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikram","family":"Gota","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology ACTREC, Tata Memorial Centre  Navi Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,18]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"Principles and Practice of Pediatric Oncology","author":"Pizzo PA","year":"2016"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25489"},{"key":"e_1_2_10_4_1","unstructured":"GUIDELINES ON SIMILAR BIOLOGICS: Regulatory Requirements for Marketing Authorization in India 2016 (2016)."},{"key":"e_1_2_10_5_1","unstructured":"NarulaG AroraB SubramanianPG et al.Outcome of B\u2010ALL Treated with A Risk\u2010Stratified and Response\u2010Adapted Protocol: Interim Analysis of A Single\u2010Institution Pilot Study for A Multicenter Collaborative Protocol from India. 49th Congress of the International Society of Paediatric Oncology (SIOP) 10\/12\/17; Washington DC: Pediatric Blood and Cancer;2017."},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008366814109"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-2697(02)00232-4"},{"key":"e_1_2_10_8_1","first-page":"656","volume-title":"Data analysis, mathematical modeling Methods of Immunological Analysis. 1","author":"Baud M","year":"1993"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.03.005"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008368916800"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25628"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-149443"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/15422119.2016.1184167"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30584-9"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.4103\/0019-509X.146723"},{"key":"e_1_2_10_16_1","unstructured":"Organization CDSC. 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