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Safety Evaluation of Ocular Drug Delivery Formulations: Techniques and Practical Considerations

From Allergan, Inc., Irvine, California, USA

Correspondence: Address correspondence to: Brian G. Short, Allergan, Inc., 2525 Dupont Dr. RD-2A, Irvine, CA 92612.

Development of new drug candidates and novel delivery techniques for treatment of ocular diseases has recently accelerated. Treatment of anterior-segment diseases has witnessed advances in prodrug formulations and permeability enhancers. Intravitreal, subconjunctival, and periocular routes of administration and sustained-release formulations of nanoparticles and microparticles, as well as nonbiodegradable and biodegradable implants to deliver drugs to the posterior segment of the eye, are becoming popular therapeutic approaches. Without adequate regulatory guidance for ocular drugs, such routes of administration and novel formulations can pose unique challenges to those involved in designing nonclinical programs, including considering clinical and nonclinical factors and choosing species, strains, and ocular toxicity parameters. Toxicologic pathologists also contribute practical experience to evaluating morphological effects of these novel formulations. Lastly, understanding species’ anatomical differences is useful for interpreting toxicological and pathological responses to the eye and is important for human risk assessment of these important new therapies for ocular diseases.

Key Words: Ocular drug delivery • intravitreal • subconjunctival • periocular • ocular implant

Abbreviations: AMD, age-related macular degeneration • CNTF, ciliary neurotrophic factor • DDS, drug delivery system • ECT, encapsulated cell technology • ERG, electroretinogram • EVA, ethylene vinyl acetate • FIHS, first in human studies • FDA, Food and Drug Administration • ICH, International Conference on Harmonization • IOP, intraocular pressure • ISO, International Standards Organization • ITV, intravitreal • NCE, new chemical entity • NZW, New Zealand White • OECD, Organisation for European Cooperation and Development • PLA, poly-lactic acid • PLGA, poly-lactic-glycolic acid • PVA, polyvinyl alcohol • RTK, receptor tyrosine kinase • TA, triamcinolone acetonide • TLRs, toll-like receptors • VEGF, vascular endothelial growth factor

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