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Immunogenicity is generally assessed to the same extent in the clinical development programs for these locally acting large molecule drug products as for biological products given systemically. However, it is uncertain whether the local route of administration bears the same clinical immunogenicity concerns relative to systemic administration. This overview examines the immunogenic potential of locally acting large molecules, summarizing the anti\u2010drug antibody incidence and its impact on pharmacokinetics, safety, and efficacy, and highlighting the specific immunogenicity risk profiles for these locally acting drugs and biologics.<\/jats:p>","DOI":"10.1002\/jcph.70298","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:27:42Z","timestamp":1790155662000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunogenicity of locally acting large molecule products: An overview"],"prefix":"10.1002","volume":"66","author":[{"given":"Lei","family":"He","sequence":"first","affiliation":[{"name":"Division of Inflammation and Immune Pharmacology Office of Clinical Pharmacology Office of Translational Science Center for Drug Evaluation and Research Food and Drug Administration  Silver Spring MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4821-9509","authenticated-orcid":false,"given":"Ping","family":"Ji","sequence":"additional","affiliation":[{"name":"Division of Inflammation and Immune Pharmacology Office of Clinical Pharmacology Office of Translational Science Center for Drug Evaluation and Research Food and Drug Administration  Silver Spring MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Golding","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Transplant Medicine Office of Immunology and Inflammation Office of New Drugs Center for Drug Evaluation and Research Food and Drug Administration  Silver Spring MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunzhao","family":"Ren","sequence":"additional","affiliation":[{"name":"Division of Inflammation and Immune Pharmacology Office of Clinical Pharmacology Office of Translational Science Center for Drug Evaluation and Research Food and Drug Administration  Silver Spring MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2443-1624","authenticated-orcid":false,"given":"Chinmay","family":"Shukla","sequence":"additional","affiliation":[{"name":"Division of Inflammation and Immune Pharmacology Office of Clinical Pharmacology Office of Translational Science Center for Drug Evaluation and Research Food and Drug Administration  Silver Spring MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Boyd","sequence":"additional","affiliation":[{"name":"Division of Ophthalmology Office of Specialty Medicine Office of New Drugs Center for Drug Evaluation and Research Food and Drug Administration  Silver Spring MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhea","family":"Lloyd","sequence":"additional","affiliation":[{"name":"Division of Ophthalmology Office of Specialty Medicine Office of New Drugs Center for Drug Evaluation and Research Food and Drug Administration  Silver Spring MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrahas","family":"Sahajwalla","sequence":"additional","affiliation":[{"name":"Division of Inflammation and Immune Pharmacology Office of Clinical Pharmacology Office of Translational Science Center for Drug Evaluation and Research Food and Drug Administration  Silver Spring MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Guidance for Industry: Immunogenicity Assessment for Therapeutic Protein Products.U.S. Food and Drug Administration. 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