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By Sibel Ucpinar

Ucpinar-finalTherapeutic equivalence concerns are frequently expressed about generic ophthalmic products. Currently, there is no general guidance published by the Food and Drug Administration (FDA) on the determination of bioequivalence for ophthalmic drug products. According to FDA, the generic drug versions must meet the same standards of quality, efficacy, and safety as their corresponding reference listed drugs. FDA has published guidance for individual products, and included therein are the Q1 and Q2 (qualitative and quantitative) considerations for demonstrating sameness. In addition, often the regulatory guidance calls for in vivo pharmacodynamic and clinical endpoints studies to demonstrate bioequivalence of the locally acting ophthalmic drug products.

There are potential issues with such in vivo approaches. Physiologically the ocular surface is a dynamic surface, and large patient populations are required to detect small differences in product performance leading to increased cost and time to run these trials. There are also possible challenges and delays in patient enrollment due to lack of drug-naive patients and at times concomitant drug administration and possibility of drug-drug interactions.

Additionally, if showing bioequivalence for ophthalmic formulations is limited to in vivo approaches, this makes drug development extremely challenging because formulation switches/changes are part of any pharmaceutical development program. Every so often, formulation adjustments become necessary due to stability issues, packaging changes, avoidance or replacement of a nonfunctional excipient, manifestation of toxicity, and/or tolerability episodes, etc. It seems impractical to address the changes in formulation strategy using both resource- and time-intensive clinical or pharmacokinetic studies in humans.

It is now increasingly important to discuss the right strategy for bioequivalence assessment of ophthalmic dosage forms. The critical physical and chemical attributes of the dosage form, use of in vitro studies, and/or animal models are all possible tools that are emerging to aid and guide ophthalmic product development and bioequivalence assessment. The goal of the sunrise session Bioequivalence Requirements for the Ophthalmic Products: CMC and Clinical/Pharmacokinetic Considerationsorganized by the AAPS Bioequivalence focus group, is to discuss alternative and advanced methodologies for optimizing formulation development and accelerating equivalence assurance of complex ophthalmic drug products. Please join us for further discussion about this on October 27!

Sibel Demirbas Ucpinar, Ph.D., is the director of Biopharmaceutics Group at Impax Laboratories, Inc., responsible for Phase I pharmacokinetic studies to support the ANDA and NDA filings. She graduated with M.S. and Ph.D. degrees from the College of Pharmacy, University of Texas, Austin.