Defining 'Best Practices' For Critical Endpoints In Preclinical Screening of New Chemical Entities For Ototoxicity Liability

Introduction: Ototoxicity has been defined as the tendency of certain therapeutic agents and other chemical substances to cause functional impairments and cellular degeneration of the tissues of the inner ear resulting in hearing loss. Objectives: This review is intended to provide details of a standardized preclinical assessment for ototoxicity under the current US FDA guidance documents that represents “industry best practices” for new drug application review of all new chemical entities being developed for human use. Methods: A literature review was conducted to assimilate study strategies that represent “Industry Best Practices” for the conduct of preclinical ototoxicity evaluation for submission to regulatory drug approval agencies. Conclusion: We have proposed a systems-approach and protocol criteria for the valid and reliable assessment of auditory function that can be easily included as a screening tool for ototoxicity within the Tiered Structure of preclinical assays required for approval of any chemical entity targeted for human use.