Regulating Generic Ophthalmologic Drug Bioequivalence—Envisioning Accessibility for Patients

Abstract

New, brand-name, ophthalmology drug products are developed, investigated, and submitted for marketing approval through premarket interactions with the Food and Drug Administration (FDA). These drug applications for novel drugs are reviewed by FDA for safety and effectiveness before being allowed on the market. Many brand-name drugs are allowed a period of marketing exclusivity and/or have patent protections that can delay generic competition. When these exclusivity periods or patents expire or are challenged (in the case of patents), generic competitors may then market equivalent products, as allowed by U.S. law (eg, Drug Price Competition and Patent Term Restoration Act, often referred to as ''the Hatch-Waxman Act''). To be approved as a therapeutic equivalent, a generic product must demonstrate that it is both pharmaceutically equivalent and bioequivalent to the brand-name drug product, which can involve innovative analytical methods and study designs. To facilitate generic drug assessment and approval, the FDA has negotiated the Generic Drug User Fee Amendments (GDUFA) program that funds a rigorous generic drug development program that includes pre-Abbreviated New Drug Application (pre-ANDA) correspondence and meetings, targeted bioequivalence research, and publication of product-specific guidances (PSGs) to support generic drug research and development for manufacturers interested in developing generic drugs for the U.S. market. FDA's regulatory practices include the monitoring of quality and postapproval adverse events of all marketed products, including those for use in and around the eyes.

Mechanistic modeling of ophthalmic, nasal, injectable, and implant generic drug products: A workshop summary report

“…In terms of ophthalmic generic products, less than 30% of the reference listed drug (RLD) products have approved generic versions on the US market for the three major ophthalmic complex dosage forms: suspensions, ointments, and emulsions 3 . For ophthalmic suspensions, a dexamethasone rabbit Ocular Compartmental Absorption and Transit (OCAT) model was developed through an FDA internal study conducted with pharmacokinetic (PK) sampling in multiple ocular tissues and plasma 4,5 .…”

“…In terms of ophthalmic generic products, less than 30% of the reference listed drug (RLD) products have approved generic versions on the US market for the three major ophthalmic complex dosage forms: suspensions, ointments, and emulsions. 3 For ophthalmic suspensions, a dexamethasone rabbit Ocular Compartmental Absorption and Transit (OCAT) model was developed through an FDA internal study conducted with pharmacokinetic (PK) sampling in multiple ocular tissues and plasma. 4,5 The model was then verified using literature PK data, with a focus on mean particle size and particle size distribution (PSD), nonlinear dose-exposure relationship, formulation viscosity, and tear dynamics impact on ocular absorption.…”

Separation Methods in Biomedical Analysis, a Booming Field

“…Many scientific endeavors are dependent upon the accurate quantification of drugs and endogenous substances, such as pharmacokinetics [1], toxicokinetics [2], and exposureresponse (pharmacokinetics/pharmacodynamics) [3]. Bioequivalence [4], for example, is a surrogate end-point used by drug companies and regulatory agencies to determine the safety/suitability of new drug formulations for approval. The use of bioequivalence can replace the need for costly and lengthy large-scale patient trials.…”