FDA's Poly (Lactic-Co-Glycolic Acid) Research Program and Regulatory Outcomes.

Poly (lactic-co-glycolic acid) (PLGA) has been used in many long-acting drug formulations which have been approved by the US Food and Drug Administration (FDA). However, generic counterparts for PLGA products have yet to gain FDA approval due to many complexities in formulation, characterization, and evaluation of test products. To address the challenges of generic development of PLGA-based products, the FDA has established an extensive research program to investigate novel methods and tools to aid both product development and regulatory review. The research focus have been: (1) analytical tools for characterization of PLGA polymers; (2) impacts of PLGA characteristics and manufacturing conditions on product performance; (3) in vitro drug release testing and in vitro-in vivo correlation of PLGA-based products, and (4) modeling tools to facilitate formulation design and bioequivalence study design of PLGA-based drugs. This article provides an overview of FDA's PLGA research program and highlights scientific accomplishments as well as regulatory outcomes that have resulted from successful research investigations.

Generic drug device combination products: Regulatory and scientific considerations.

Complex regulatory and scientific considerations exist for drug-device combination products submitted under an Abbreviated New Drug Application. The Agency has published several guidances to aid industry in the development of a generic drug-device combination product: providing recommendations on the types of studies necessary to establish bioequivalence, providing considerations on product quality and performance for certain types of device constituents, and most recently, providing tools to assess the proposed user interface when compared to the user interface of the Reference Listed Drug. In addition, the Office of Generic Drugs1 has established a regulatory science research program intended to support projects that examine scientific questions relating to the development of generic combination products and their associated regulatory review. Several research examples are described within this article, which demonstrate how equivalence can be evaluated when the function of the device could potentially impact drug delivery. Moreover, this article provides an overview of regulatory recommendations and ongoing scientific research efforts to further develop guidances and ultimately improve public access to generic combination products.

Clinical, Pharmacokinetic, and In Vitro Studies to Support Bioequivalence of Ophthalmic Drug Products.

For ophthalmic drug products, the determination of bioequivalence can be challenging, as drug concentrations at the site of action cannot always be measured. The FDA has recommended a variety of studies that can be used to demonstrate bioequivalence for different ophthalmic drug products. Product-specific bioequivalence recommendations for 28 ophthalmic products have been posted on FDA's website as of May 2016, outlining the specific tests which should be performed to demonstrate bioequivalence. The type of study that can be used to demonstrate bioequivalence depends on the drug product's active pharmaceutical ingredient(s), dosage form, indication, site of action, mechanism of action, and scientific understanding of drug release/drug availability and drug product characteristics. This article outlines the FDA's current guidance on studies to demonstrate bioequivalence through clinical endpoint studies, pharmacokinetic studies, and in vitro studies for generic ophthalmic drug products.