Critical appraisal of alternative irritation models: three decades of testing ophthalmic pharmaceuticals

Abdelkader, Hamdy and Pierscionek, Barbara K. and Carew, Mark and Wu, Zimei and Alany, Raid G. (2015) Critical appraisal of alternative irritation models: three decades of testing ophthalmic pharmaceuticals. British Medical Bulletin, 113 (1). pp. 59-71. ISSN 1471-8391

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Background: Testing ocular tolerability of ocular pharmaceuticals is an essential regulatory requirement. The current approved reference model (gold standard) for ocular irritation testing is the Draize test. However this method is subjective and involves using live animals, hence the need to develop alternative in vitro and ex vivo testing strategies. Source of data: Pubmed, Science Direct, Scopus, Google Scholar, Medline, Current Content, Web of Science and validation reports from international regulatory bodies; The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and European Centre for the Validation of Alternative Methods (ECVAM) were searched for in vitro alternatives. Area of agreement: Whilst no single in vitro test can effectively replace the Draize eye irritation test, regulatory bodies and cosmetic/pharmaceutical industries agree that there is a need for in vitro alternatives with validated endpoints to evaluate pharmaceutical ingredients and finished eye products. Area of controversy: There is no single in vitro test / assay that can predict the ocular irritation potential of mild to moderate test substances. Area timely for developing research: This review provides a critical appraisal of the selected in vitro and ex vivo ocular toxicity models recommended by international regulatory bodies. These include cytotoxicity methods, biochemical systems and ex vivo assays. The latter are approved by ECVAM as in vitro alternatives for the well-known Draize test. Hen's egg test-chorioallantoic membrane and the isolated rabbit eye test are also accepted by regulatory agencies in France, Germany, the Netherlands and the UK. A combination of ex vivo assays along with histological examination of excised bovine cornea can predict the conjunctival and corneal tolerability and cover a wider range of ocular pharmaceutical substances.

Item Type: Journal Article
Keywords: Draize test, ocular toxicity, irritation, cornea, hen's egg chorioallantoic membrane, bovine cornea, opacity and permeability
Faculty: ARCHIVED Faculty of Health, Social Care & Education (until September 2018)
Depositing User: Lisa Blanshard
Date Deposited: 22 Feb 2021 11:24
Last Modified: 09 Sep 2021 16:15

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