Toxicity Testing for Ocular Drug Products

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

“…Some FDA guidance that is a decade old is published in brief form (Avalos et al, 1997;Weir et al, 1999). Some differences exist among or within U.S., European, and Japanese regulatory agencies.…”

“…There is relatively little International Conference on Harmonization (ICH) guidance of regulatory expectations for nonclinical toxicity and pharmacokinetic studies needed for ocular drugs, including those with novel delivery approaches. Some FDA guidance that is a decade old is published in brief form (Avalos et al, 1997; Weir et al, 1999). Some differences exist among or within U.S., European, and Japanese regulatory agencies.…”

“…Before conduction of pivotal repeat-dose ocular studies, an assessment of the ocular tolerability of the test article should be conducted. Review of physiochemical properties (e.g., pH), structure-activity relationships, and in vitro assays to evaluate irritancy and ocular tolerability are practiced routinely in this laboratory with an NCE or a reformulation containing new excipients or vehicles and are beyond the scope of this review (Avalos et al, 1997). Ocular tolerance studies are recommended by European regulatory authorities (CPMP/SWP/21/00) and usually consist of a single-dose study in a small number of rabbits (1 to 3), with a 20 to 30 μl drop size in a single dose/ concentration with hourly observation and scoring (modification of Draize scoring system), with an increase in concentration or frequency over several days and evaluation by slit-lamp biomicroscopy.…”

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

“…1,7 On the regulatory side, there is relatively little guidance from the International Conference on Harmonisation (ICH) for non-clinical toxicity studies on ocular drugs, including those with novel additives. 8,9 European regulatory authorities recommend an in vivo ocular tolerance study (CPMMP/SWP/21/ 00), where a single dose (20-30 µl) of the test formulation is investigated in a small number of New Zealand white rabbits (one to three) for any ocular abnormalities that are recorded and scored. 9 The standard in vivo eye test (Draize eye test) has been around since 1940s.…”