{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:50:52Z","timestamp":1791615052913,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012895","name":"Zoetis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012895","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Pharm &amp; Therapeutics"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Monoclonal antibodies (mAbs) represent a rapidly expanding pharmaceutical class in veterinary medicine, with several products now authorized for use in dogs and cats. Limited published articles and veterinarian exposure to the principles of drug development present challenges in interpreting published safety evaluations that inform product labeling and clinical use. This review describes the principles, methods, strengths, limitations, and interpretation of preclinical target animal safety (TAS) studies for veterinary mAbs and is intended to equip veterinarians and researchers with the knowledge to critically evaluate published TAS data and understand how preclinical safety evidence translates to product labeling. TAS studies are conducted in healthy, purpose\u2010bred animals of the target species using a margin of safety (MOS) approach with supratherapeutic dosing to screen for product risks. The regulatory and scientific framework is based on internationally harmonized guidance for safety evaluation of small molecule therapeutics in veterinary medicine and more than four decades of experience with mAb therapeutics in human medicine. The high target specificity of the mAb drug class enables a hypothesis\u2010driven evaluation strategy, combining standard endpoints with target\u2010informed specialized assessments. Terminal gross and histopathological endpoints provide safety data that clinical studies cannot generate, identifying potential adverse effects down to the cellular level. Unique to veterinary medicine, these data are generated directly in the target species. Data interpretation follows a weight\u2010of\u2010evidence approach in which findings are presumed treatment\u2010related until demonstrated otherwise, integrating dose\u2013response relationships, biological plausibility, and both study and historical control data. TAS studies complement the broader safety evaluation continuum, including clinical field studies, pharmacovigilance, and independent research.<\/jats:p>","DOI":"10.1111\/jvp.70116","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:41:24Z","timestamp":1791614484000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical Target Animal Safety Evaluation of Veterinary Monoclonal Antibodies: Principles, Methods, and Interpretation"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7472-4095","authenticated-orcid":false,"given":"Adam","family":"Werts","sequence":"first","affiliation":[{"name":"Global Therapeutics, Clinical Pharmacology and Safety Sciences Zoetis Inc  Kalamazoo Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0119-8325","authenticated-orcid":false,"given":"Matthew","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Global Therapeutics, Clinical Pharmacology and Safety Sciences Zoetis Inc  Kalamazoo Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Bessey","sequence":"additional","affiliation":[{"name":"Global Therapeutics, Clinical Pharmacology and Safety Sciences Zoetis Inc  Kalamazoo Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0214-2320","authenticated-orcid":false,"given":"Alicia Braxton","family":"Hickman","sequence":"additional","affiliation":[{"name":"Global Therapeutics, Clinical Pharmacology and Safety Sciences Zoetis Inc  Kalamazoo Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Chory","sequence":"additional","affiliation":[{"name":"Global Therapeutics, Clinical Pharmacology and Safety Sciences Zoetis Inc  Kalamazoo Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Global Therapeutics, Clinical Pharmacology and Safety Sciences Zoetis Inc  Kalamazoo Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirby","family":"Pasloske","sequence":"additional","affiliation":[{"name":"Global Therapeutics, Clinical Pharmacology and Safety Sciences Zoetis Inc  Kalamazoo Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"e_1_2_15_2_1","volume-title":"Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays","author":"Albretsen J.","year":"2024"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535\u2010008\u20102266\u20106"},{"issue":"8","key":"e_1_2_15_4_1","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1177\/01926233221135563","article-title":"Scientific and Regulatory Policy Committee Best Practices: Recommended (\u201cBest\u201d) Practices for Informed (Non\u2010Blinded) Versus Masked (Blinded) Microscopic Evaluation in Animal Toxicity Studies","volume":"50","author":"Bolon B.","year":"2022","journal-title":"Toxicologic Pathology"},{"key":"e_1_2_15_5_1","first-page":"207","volume-title":"Drug Safety Evaluation: Methods and Protocols","author":"Brennan R. J.","year":"2017"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2022.105329"},{"key":"e_1_2_15_7_1","unstructured":"Code of Federal Regulations.1978.\u201c21 C.F.R. Part 58: Good Laboratory Practice for Nonclinical Laboratory Studies.\u201dhttps:\/\/www.ecfr.gov\/current\/title\u201021\/chapter\u2010I\/subchapter\u2010A\/part\u201058."},{"key":"e_1_2_15_8_1","volume-title":"Guidelines for Preparing Core Clinical Safety Information on Drugs: Report of CIOMS Working Groups III and V","author":"Council for International Organizations of Medical Sciences (CIOMS)","year":"2017"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2025.1550468"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010bioeng\u2010082721\u2010024500"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/vetr.4023"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.18849\/ve.v9i3.682"},{"key":"e_1_2_15_13_1","volume-title":"Comprehensive Toxicology","author":"Foster J. R.","year":"2022"},{"key":"e_1_2_15_14_1","volume-title":"Histopathology of Preclinical Toxicity Studies: Interpretation and Relevance in Drug Safety Evaluation","author":"Greaves P.","year":"2012"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.DMPK\u201010\u2010RV\u2010062"},{"issue":"2","key":"e_1_2_15_16_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s40259-023-00641-2","article-title":"Reducing Immunogenicity by Design: Approaches to Minimize Immunogenicity of Monoclonal Antibodies","volume":"38","author":"Harris C. T.","year":"2024","journal-title":"BioDrugs"},{"key":"e_1_2_15_17_1","unstructured":"International Council for Harmonisation.1994.Toxicokinetics: A Guidance for Assessing Systemic Exposure in Toxicology StudiesICH S3A."},{"key":"e_1_2_15_18_1","unstructured":"International Council for Harmonisation.2004.Comparability of Biotechnological\/Biological Products Subject to Changes in Their Manufacturing ProcessICH Q5E."},{"key":"e_1_2_15_19_1","unstructured":"International Council for Harmonisation.2011.Preclinical Safety Evaluation of Biotechnology\u2010Derived PharmaceuticalsICH S6(R1)."},{"key":"e_1_2_15_20_1","volume-title":"Immunobiology: The Immune System in Health and Disease","author":"Janeway C. A.","year":"2001"},{"issue":"1","key":"e_1_2_15_21_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/rtph.1996.1076","article-title":"A Systematic Approach for Evaluating the Quality of Experimental Toxicological and Ecotoxicological Data","volume":"25","author":"Klimisch H. J.","year":"1997","journal-title":"Regulatory Toxicology and Pharmacology"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.2.3.11782"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010023\u201003627\u20105"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20178"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.2011.01812.x"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.2984"},{"key":"e_1_2_15_27_1","doi-asserted-by":"crossref","DOI":"10.3389\/fvets.2025.1558222","article-title":"Global Pharmacovigilance Reporting of the First Monoclonal Antibody for Canine Osteoarthritis: A Case Study With Bedinvetmab (Librela)","volume":"12","author":"Monteiro B. P.","year":"2025","journal-title":"Frontiers in Veterinary Science"},{"key":"e_1_2_15_28_1","doi-asserted-by":"publisher","DOI":"10.2460\/javma.24.10.0665"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010022\u201000633\u2010x"},{"key":"e_1_2_15_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2024.2443538"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2155"},{"key":"e_1_2_15_33_1","volume-title":"The Principles of Humane Experimental Technique","author":"Russell W. M. S.","year":"1959"},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230701595300"},{"key":"e_1_2_15_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928\u2010011\u20109232\u20102"},{"issue":"4","key":"e_1_2_15_36_1","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1208\/s12248-014-9599-2","article-title":"Assessment and Reporting of the Clinical Immunogenicity of Therapeutic Proteins and Peptides: Harmonized Terminology and Tactical Recommendations","volume":"16","author":"Shankar G.","year":"2014","journal-title":"AAPS Journal"},{"key":"e_1_2_15_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40199\u2010023\u201000486\u20108"},{"issue":"6","key":"e_1_2_15_38_1","doi-asserted-by":"crossref","first-page":"871","DOI":"10.2165\/00003495-198937060-00004","article-title":"Muromonab CD3: A Review of Its Pharmacology and Therapeutic Potential","volume":"37","author":"Todd P. A.","year":"1989","journal-title":"Drugs"},{"key":"e_1_2_15_39_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center for Veterinary Medicine.2011.Target Animal Safety and Effectiveness Protocol Development and SubmissionFDA CVM GFI #215."},{"key":"e_1_2_15_40_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center for Veterinary Medicine.2016.Target Animal Safety Data Presentation and Statistical AnalysisFDA CVM GFI #226."},{"key":"e_1_2_15_41_1","unstructured":"U.S. Food and Drug Administration. n.d.\u201cFreedom of information (FOI) summaries for approved and conditionally approved animal drugs.\u201dhttps:\/\/www.fda.gov\/animal\u2010veterinary\/approved\u2010animal\u2010drug\u2010products\u2010green\u2010book\/freedom\u2010information\u2010foi\u2010summaries\u2010approved\u2010and\u2010conditionally\u2010approved\u2010animal\u2010drugs."},{"key":"e_1_2_15_42_1","unstructured":"U.S. Food and Drug Administration Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research.2019.\u201cImmunogenicity Testing of Therapeutic Protein Products \u2010 Developing and Validating Assays for Anti\u2010Drug Antibody Detection: Guidance for Industry.\u201d"},{"key":"e_1_2_15_43_1","unstructured":"U.S. Food and Drug Administration Center for Veterinary Medicine.2001.\u201cGuidance for Industry: Good Clinical Practice (VICH GL9).\u201dhttps:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/good\u2010clinical\u2010practice\u2010vich\u2010gl9."},{"key":"e_1_2_15_44_1","volume-title":"Target Animal Safety for Veterinary Pharmaceutical Products","author":"VICH GL43","year":"2008"},{"key":"e_1_2_15_45_1","unstructured":"VICH GL62. (Step 4 draft September 2025; consultation closed February 2026).2025.\u201cTarget Animal Safety Evaluation for Veterinary Monoclonal Antibody Products (VMAPs).\u201dEuropean Medicines Agency EMEA\/CVMP\/VICH\/250843\/2021."},{"key":"e_1_2_15_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani15040472"},{"key":"e_1_2_15_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238\u2010017\u20100473\u20108"},{"issue":"3","key":"e_1_2_15_48_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1365-2885.2005.00650.x","article-title":"Veterinary Pharmacovigilance. Part 6. Predictability of Adverse Reactions in Animals From Laboratory Toxicology Studies","volume":"28","author":"Woodward K. N.","year":"2005","journal-title":"Journal of Veterinary Pharmacology and Therapeutics"},{"issue":"2","key":"e_1_2_15_49_1","first-page":"131","article-title":"Veterinary Pharmacovigilance. Part 1. The Genesis of Pharmacovigilance and Its Aims and Objectives","volume":"28","author":"Woodward K. N.","year":"2005","journal-title":"Journal of Veterinary Pharmacology and Therapeutics"},{"key":"e_1_2_15_50_1","first-page":"165","volume-title":"WHO Expert Committee on Specifications for Pharmaceutical Preparations: Fiftieth Report","author":"World Health Organization (WHO)","year":"2016"}],"container-title":["Journal of Veterinary Pharmacology and Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvp.70116","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jvp.70116","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvp.70116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:41:29Z","timestamp":1791614489000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvp.70116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,9]]},"references-count":49,"alternative-id":["10.1111\/jvp.70116"],"URL":"https:\/\/doi.org\/10.1111\/jvp.70116","archive":["Portico"],"relation":{},"ISSN":["0140-7783","1365-2885"],"issn-type":[{"value":"0140-7783","type":"print"},{"value":"1365-2885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,9]]},"assertion":[{"value":"2026-06-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"jvp.70116"}}