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DRUG DELIVERY
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FDA’s Regulatory Science Program for Generic PLA/ PLGA-Based Drug Products
Yan Wang1
Research, FDA 2
, Wen Qu2 , Stephanie H. Choi1 1Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and
Office of Lifecycle Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, FDA
Introduction
Polylactide (PLA)/Poly(lactide-co-glycolide) (PLGA) is widely used in many FDA-approved drug products. There are currently 15 FDA-ap- proved PLA/PLGA-based drug products available on the US market (Table 1). PLA/PLGA-based drug products are designed to reduce dosing frequency and potential drug toxicity. They are also useful for improving patient compliance with a better therapeutic option to treat patients who adhere poorly to frequent oral or injectable medication. However, as these products are generally expensive, the availability of generic PLA/PLGA-based counterparts would make them more affordable, more widely available, and thus benefitting more patients.
This article reflects the views of the authors and should not be construed to represent FDA’s views or policies.
To gain FDA approval, generic drug products must demonstrate phar- maceutical equivalence and bioequivalence to the reference listed drug (RLD). Pharmaceutical equivalence requires that the drug product contains the same active ingredient(s) as the RLD, be identical in strength, dosage form, and route of administration, and that it meets compendial or other applicable standards of strength, quality, purity, and identity. Bioequivalence requires an absence of a significant difference in the rate and extent to which the active ingredient in pharmaceutically equivalent products becomes available at the site of action. For injectable PLA/PLGA-based drug products, the test product should be qualitatively (Q1) and quantitatively (Q2) the same as the RLD to be considered for approval in an Abbreviated New Drug Application (ANDA).1
Differences in PLA/PLGA characteristics can vastly alter the drug release mechanism and release rate. As a random copolymer, the inherent heterogeneity associated with PLA/PLGA makes determination of Q1 sameness of the PLA/PLGA very challenging. Identifying the key characteristics of PLA/PLGA is critical for developing appropriate regulatory standards to determine Q1 sameness of PLA/PLGA and pharmaceutical equivalence between the test and reference products.
14 | | May/June 2016
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