{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:08:41Z","timestamp":1787771321539,"version":"build-2784847793"},"reference-count":52,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,13]],"date-time":"2020-06-13T00:00:00Z","timestamp":1592006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007819","name":"Allergan","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100007819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Differences in botulinum neurotoxin manufacturing, formulation, and potency evaluation can impact dose and biological activity, which ultimately affect duration of action. The potency of different labeled vials of incobotulinumtoxinA (Xeomin\u00ae; 50 U, 100 U, or 200 U vials; incobotA) versus onabotulinumtoxinA (BOTOX\u00ae; 100 U vial; onabotA) were compared on a unit-to-unit basis to assess biological activity using in vitro (light-chain activity high-performance liquid chromatography (LCA-HPLC) and cell-based potency assay (CBPA)) and in vivo (rat compound muscle action potential (CMAP) and mouse digit abduction score (DAS)) assays. Using LCA-HPLC, incobotA units displayed approximately 54% of the protease activity of label-stated equivalent onabotA units. Lower potency, reflected by higher EC50, ID50, and ED50 values (pooled mean \u00b1 SEM), was displayed by incobotA compared to onabotA in the CBPA (EC50: incobotA 7.6 \u00b1 0.7 U\/mL; onabotA 5.9 \u00b1 0.5 U\/mL), CMAP (ID50: incobotA 0.078 \u00b1 0.005 U\/rat; onabotA 0.053 \u00b1 0.004 U\/rat), and DAS (ED50: incobotA 14.2 \u00b1 0.5 U\/kg; onabotA 8.7 \u00b1 0.3 U\/kg) assays. Lastly, in the DAS assay, onabotA had a longer duration of action compared to incobotA when dosed at label-stated equivalent units. In summary, onabotA consistently displayed greater biological activity than incobotA in two in vitro and two in vivo assays. Differences in the assay results do not support dose interchangeability between the two products.<\/jats:p>","DOI":"10.3390\/toxins12060393","type":"journal-article","created":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T00:50:49Z","timestamp":1592268649000},"page":"393","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["OnabotulinumtoxinA Displays Greater Biological Activity Compared to IncobotulinumtoxinA, Demonstrating Non-Interchangeability in Both In Vitro and In Vivo Assays"],"prefix":"10.3390","volume":"12","author":[{"given":"David","family":"Rupp","sequence":"first","affiliation":[{"name":"Allergan, an AbbVie company, Irvine, CA 92612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Nicholson","sequence":"additional","affiliation":[{"name":"Allergan, an AbbVie company, Irvine, CA 92612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Canty","sequence":"additional","affiliation":[{"name":"Allergan, an AbbVie company, Irvine, CA 92612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Wang","sequence":"additional","affiliation":[{"name":"Allergan, an AbbVie company, Irvine, CA 92612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9310-6044","authenticated-orcid":false,"given":"Catherine","family":"Rh\u00e9aume","sequence":"additional","affiliation":[{"name":"Allergan, an AbbVie company, Irvine, CA 92612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linh","family":"Le","sequence":"additional","affiliation":[{"name":"Allergan, an AbbVie company, Irvine, CA 92612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance E.","family":"Steward","sequence":"additional","affiliation":[{"name":"Allergan, an AbbVie company, Irvine, CA 92612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Washburn","sequence":"additional","affiliation":[{"name":"Allergan, an AbbVie company, Irvine, CA 92612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitte P.","family":"Jacky","sequence":"additional","affiliation":[{"name":"Allergan, an AbbVie company, Irvine, CA 92612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron S.","family":"Broide","sequence":"additional","affiliation":[{"name":"Allergan, an AbbVie company, Irvine, CA 92612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang G.","family":"Philipp-Dormston","sequence":"additional","affiliation":[{"name":"Faculty of Health, University Witten\/Herdecke, 58455 Witten, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell F.","family":"Brin","sequence":"additional","affiliation":[{"name":"Allergan, an AbbVie company, Irvine, CA 92612, USA"},{"name":"Department of Neurology, University of California, Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Brideau-Andersen","sequence":"additional","affiliation":[{"name":"Allergan, an AbbVie company, Irvine, CA 92612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1159\/000083259","article-title":"Botulinum Toxin: Mechanisms of Action","volume":"53","author":"Dressler","year":"2005","journal-title":"Eur. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1152\/physrev.2000.80.2.717","article-title":"Neurotoxins affecting neuroexocytosis","volume":"80","author":"Schiavo","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1124\/pr.116.012658","article-title":"Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology","volume":"69","author":"Pirazzini","year":"2017","journal-title":"Pharmacol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1128\/iai.64.5.1589-1594.1996","article-title":"Molecular composition of Clostridium botulinum type A progenitor toxins","volume":"64","author":"Inoue","year":"1996","journal-title":"Infect. Immun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.toxicon.2013.02.014","article-title":"The life history of a botulinum toxin molecule","volume":"68","author":"Simpson","year":"2013","journal-title":"Toxicon"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.cps.2016.03.003","article-title":"Overview of Botulinum Toxins for Aesthetic Uses","volume":"43","author":"Gart","year":"2016","journal-title":"Clin. Plast. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1128\/mr.56.1.80-99.1992","article-title":"Properties and use of botulinum toxin and other microbial neurotoxins in medicine","volume":"56","author":"Schantz","year":"1992","journal-title":"Microbiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S77","DOI":"10.1016\/S0151-9638(09)74532-6","article-title":"Different botulinum toxins and their specifications","volume":"136","author":"Beylot","year":"2009","journal-title":"Ann. Dermatol. Venereol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/BF00839205","article-title":"Clostridium botulinum toxins: A general review of involvement in disease, structure, mode of action and preparation for clinical use","volume":"239","author":"Hambleton","year":"1992","journal-title":"J. Neurol."},{"key":"ref_10","unstructured":"Federal Drug Administration (FDA) (2009, September 21). Center for drug evaluation and research, application number: 125274, Available online: http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2009\/125274s000_ChemR.pdf."},{"key":"ref_11","first-page":"325","article-title":"Complexing proteins in botulinum toxin type A drugs: A help or a hindrance?","volume":"4","author":"Frevert","year":"2010","journal-title":"Boil. Targets Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/ijd.12627","article-title":"Comparative trial of a novel botulinum neurotoxin type A versus onabotulinumtoxinA in the treatment of glabellar lines: A multicenter, randomized, double-blind, active-controlled study","volume":"54","author":"Won","year":"2014","journal-title":"Int. J. Dermatol."},{"key":"ref_13","first-page":"227","article-title":"Botulinum toxin type A products are not interchangeable: A review of the evidence","volume":"8","author":"Brin","year":"2014","journal-title":"Boil. Targets Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1097\/WNO.0000000000000110","article-title":"A direct comparison of onabotulinumtoxinA (botox) and incobotulinumtoxinA (xeomin) in the treatment of benign essential blepharospasm: A split-face technique","volume":"34","author":"Saad","year":"2014","journal-title":"J. Neuroophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s00702-014-1253-8","article-title":"Botulinum toxin therapy of cervical dystonia: Duration of therapeutic effects","volume":"122","author":"Dressler","year":"2014","journal-title":"J. Neural Transm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"211","DOI":"10.2147\/CCID.S41537","article-title":"Onset and duration of effect of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA in the treatment of glabellar frown lines: A randomized, double-blind study","volume":"6","author":"Rappl","year":"2013","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1111\/j.1524-4725.2010.01706.x","article-title":"Noninferiority of IncobotulinumtoxinA, Free from Complexing Proteins, Compared with Another Botulinum Toxin Type A in the Treatment of Glabellar Frown Lines","volume":"36","author":"Sattler","year":"2010","journal-title":"Dermatol. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1097\/DSS.0000000000000531","article-title":"A Randomized, Double-Blind Trial to Investigate the Equivalence of IncobotulinumtoxinA and OnabotulinumtoxinA for Glabellar Frown Lines","volume":"41","author":"Kane","year":"2015","journal-title":"Dermatol. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.2147\/DDDT.S79193","article-title":"Clinical and pharmacological properties of incobotulinumtoxinA and its use in neurological disorders","volume":"9","author":"Jost","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40268-014-0077-1","article-title":"Pharmaceutical, biological, and clinical properties of botulinum neurotoxin type A products","volume":"15","author":"Frevert","year":"2015","journal-title":"Drugs R D"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00702-014-1278-z","article-title":"Blepharospasm: Long-term treatment with either botox\u00ae, xeomin\u00ae or dysport\u00ae","volume":"122","author":"Kollewe","year":"2015","journal-title":"J. Neural Transm."},{"key":"ref_22","unstructured":"Merz Pharma UK Ltd. (2019, January 14). Xeomin 200 Units Summary of Product Characteristics (SMPC). Available online: https:\/\/www.medicines.org.uk\/emc\/product\/2162\/smpc\/print."},{"key":"ref_23","unstructured":"Merz Pharma UK Ltd. (2019, May 09). Bocouture 50 Units Summary of Product Characteristics (SMPC). Available online: https:\/\/www.medicines.org.uk\/emc\/product\/600\/smpc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3109\/14764172.2012.738913","article-title":"A randomised, double-blind comparison of 20 units of onabotulinumtoxinA with 30 units of incobotulinumtoxinA for glabellar lines","volume":"14","author":"Dirschka","year":"2012","journal-title":"J. Cosmet. Laser Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1097\/PRS.0000000000001255","article-title":"A Prospective, Split-Face, Randomized, Double-Blind Study Comparing OnabotulinumtoxinA to IncobotulinumtoxinA for Upper Face Wrinkles","volume":"135","author":"Yeilding","year":"2015","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"413e","DOI":"10.1097\/PRS.0b013e318170813c","article-title":"Comparisons among Botulinum Toxins: An Evidence-Based Review","volume":"121","author":"Klein","year":"2008","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s00702-012-0854-3","article-title":"Comparative evaluation of the potency and antigenicity of two distinct BoNT\/A-derived formulations","volume":"120","author":"Brown","year":"2012","journal-title":"J. Neural Transm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.3390\/toxins2082198","article-title":"Characterization of SNARE Cleavage Products Generated by Formulated Botulinum Neurotoxin Type-A Drug Products","volume":"2","author":"Hunt","year":"2010","journal-title":"Toxins"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1097\/WNF.0b013e3181692735","article-title":"Potency Evaluation of a Formulated Drug Product Containing 150-kd Botulinum Neurotoxin Type A","volume":"32","author":"Hunt","year":"2008","journal-title":"Clin. Neuropharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"67","DOI":"10.2165\/11584780-000000000-00000","article-title":"Content of botulinum neurotoxin in botox\u00ae\/vistabel\u00ae, dysport\u00ae\/azzalure\u00ae, and xeomin\u00ae\/bocouture\u00ae","volume":"10","author":"Frevert","year":"2010","journal-title":"Drugs R D"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00702-011-0719-1","article-title":"Measuring the potency labelling of onabotulinumtoxinA (Botox\u00ae) and incobotulinumtoxinA (Xeomin\u00ae) in an LD50 assay","volume":"119","author":"Dressler","year":"2011","journal-title":"J. Neural Transm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.neulet.2016.06.001","article-title":"In-Vivo comparison of the neurotoxic potencies of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA","volume":"627","author":"Kutschenko","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Fernandez-Salas, E., Wang, J., Molina, Y., Nelson, J.B., Jacky, B.P.S., and Aoki, K.R. (2012). Botulinum Neurotoxin Serotype a Specific Cell-Based Potency Assay to Replace the Mouse Bioassay. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049516"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.toxicon.2009.09.005","article-title":"Quantitative determination of biological activity of botulinum toxins utilizing compound muscle action potentials (CMAP), and comparison of neuromuscular transmission blockage and muscle flaccidity among toxins","volume":"55","author":"Torii","year":"2010","journal-title":"Toxicon"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"s3","DOI":"10.1111\/j.1468-1331.1999.tb00032.x","article-title":"Preclinical update on BOTOX\u00ae (botulinum toxin type A)-purified neurotoxin complex relative to other botulinurn neurotoxin preparations","volume":"6","author":"Aoki","year":"1999","journal-title":"Eur. J. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.toxicon.2013.05.004","article-title":"The rat Digit Abduction Score (DAS) assay: A physiological model for assessing botulinum neurotoxin-induced skeletal muscle paralysis","volume":"71","author":"Broide","year":"2013","journal-title":"Toxicon"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1097\/DSS.0000000000001076","article-title":"IncobotulinumtoxinA for Aesthetic Indications","volume":"43","author":"Prager","year":"2017","journal-title":"Dermatol. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Scaglione, F. (2016). Conversion ratio between botox\u00ae, dysport\u00ae, and xeomin\u00ae in clinical practice. Toxins, 8.","DOI":"10.3390\/toxins8030065"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1097\/PRS.0000000000002076","article-title":"A quantitative analysis of onabotulinumtoxinA, abobotulinumtoxinA, and incobotulinumtoxinA: A randomized, double-blind, prospective clinical trial of comparative dynamic strain reduction","volume":"137","author":"Wilson","year":"2016","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_40","first-page":"993","article-title":"Six-Month Comparative Analysis Monitoring the Progression of the Largest Diameter of the Sweating Inhibition Halo of Different Botulinum Toxins Type-A","volume":"39","author":"Pereira","year":"2018","journal-title":"Aesthetic Surg. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1177\/1090820X13503475","article-title":"The south american glabellar experience study (sage): A multicenter retrospective analysis of real-world treatment patterns following the introduction of incobotulinumtoxinA in argentina","volume":"33","author":"Banegas","year":"2013","journal-title":"Aesthetic Surg. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1097\/DSS.0000000000000704","article-title":"Repeated OnabotulinumtoxinA Treatment of Glabellar Lines at Rest Over Three Treatment Cycles","volume":"42","author":"Carruthers","year":"2016","journal-title":"Dermatol. Surg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"669","DOI":"10.2165\/00003495-200767050-00003","article-title":"Botulinum Neurotoxin Type A Free of Complexing Proteins (XEOMIN\u00ae) in Focal Dystonia","volume":"67","author":"Jost","year":"2007","journal-title":"Drugs"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1212\/01.WNL.0000163767.99354.C3","article-title":"A new botulinum toxin type A free of complexing proteins for treatment of cervical dystonia","volume":"64","author":"Benecke","year":"2005","journal-title":"Neurology"},{"key":"ref_45","unstructured":"Merz Pharma UK Ltd. (2020, January 14). Xeomin\u00ae (incobotulinumtoxinA). Available online: https:\/\/www.xeominaesthetic.com\/wp-content\/uploads\/2019\/05\/XEOMIN-Full-Prescribing-Information-including-MedGuide.pdf."},{"key":"ref_46","unstructured":"Allergan plc (2019, December 17). Botox\u00ae (onabotulinumtoxinA). Available online: https:\/\/media.allergan.com\/actavis\/actavis\/media\/allergan-pdf-documents\/product-prescribing\/20190620-BOTOX-100-and-200-Units-v3-0USPI1145-v2-0MG1145.pdf."},{"key":"ref_47","unstructured":"Ipsen Biopharmaceuticals Inc (2020, January 14). Dysport\u00ae (abobotulinumtoxinA), Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2016\/125274s107lbl.pdf."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.biologicals.2003.08.001","article-title":"Role for standards in assays of botulinum toxins: International collaborative study of three preparations of botulinum type A toxin","volume":"31","author":"Sesardic","year":"2003","journal-title":"Boilogicals"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0379-0738(00)00362-5","article-title":"Analysis of gastrocnemius compound muscle action potential in rat after death: Significance for the estimation of early postmortem interval","volume":"116","author":"Elmas","year":"2001","journal-title":"Forensic Sci. Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.toxicon.2009.06.020","article-title":"Quantitative determination of the biological activity of botulinum toxin type A by measuring the compound muscle action potential (CMAP) in rats","volume":"54","author":"Sakamoto","year":"2009","journal-title":"Toxicon"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Kwak, S., Kang, W.-H., Rhee, C.-H., Yang, G.-H., and Cruz, D.J.M. (2020). Comparative Pharmacodynamics Study of 3 Different Botulinum Toxin Type A Preparations in Mice. Dermatol. Surg.","DOI":"10.1097\/DSS.0000000000002402"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.toxicon.2015.06.021","article-title":"In Vivo onset and duration of action varies for botulinum neurotoxin A subtypes 1-5","volume":"107","author":"Pellett","year":"2015","journal-title":"Toxicon"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/12\/6\/393\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:38:44Z","timestamp":1760175524000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/12\/6\/393"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,13]]},"references-count":52,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["toxins12060393"],"URL":"https:\/\/doi.org\/10.3390\/toxins12060393","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,13]]}}}