Manuscript “Complex Sameness” From Akina, Inc.-FDA Research Highlights Q1/Q2 Assay Methodologies

In addition to providing polymer products through the PolySciTech product line, Akina, Inc. also provides analytical and research services through the Akinalytics division (http://www.akinalytics.com/). A recent publication relates the development work performed with the Food and Drug Administration to deconstruct microparticle formulations which are constructed of more than one type of PLGA (varying lactide ratio) by applying a series of semi-solvents which dissolve higher-lactide content PLGA sequentially so each fraction can be assayed. Trelstar ® 22.5 mg dose was deconstructed by this method and each fraction was assayed. This research holds promise to develop assays which enable determination of sameness between Reference-Listed Drug (RLD) and a proposed generic. Read more: Skidmore, Sarah, Justin Hadar, John Garner, Haesun Park, Kinam Park, Yan Wang, and Xiaohui Jiang. “Complex sameness: Separation of mixed poly (lactide-co-glycolide) s based on the lactide: glycolide ratio.” Journal of Controlled Release (2019). https://doi.org/10.1016/j.jconrel.2019.03.002 [Link for 50-Days of Free access (May 5, 2019): https://authors.elsevier.com/c/1YjxgcI2~p~xz]

“Abstract: Poly (lactide-co-glycolide) (PLGA) has been used for making injectable, long-acting depot formulations for the last three decades. An in depth understanding of PLGA polymers is critical for development of depot formulations as their properties control drug release kinetics. To date, about 20 PLGA-based formulations have been approved by the U.S. Food and Drug Administration (FDA) through new drug applications, and none of them have generic counterparts on the market yet. The lack of generic PLGA products is partly due to difficulties in reverse engineering. A generic injectable PLGA product is required to establish qualitative and quantitative (Q1/Q2) sameness of PLGA to that of a reference listed drug (RLD) to obtain an approval from the FDA. Conventional characterizations of PLGA used in a formulation rely on measuring the molecular weight by gel permeation chromatography (GPC) based on polystyrene molecular weight standards, and determining the lactide:glycolide (L: G) ratio by 1H NMR and the end-group by 13C NMR. These approaches, however, may not be suitable or sufficient, if a formulation has more than one type of PLGA, especially when they have similar molecular weights, but different L:G ratios. Accordingly, there is a need to develop new assay methods for separating PLGAs possessing different L:G ratios when used in a drug product and characterizing individual PLGAs. The current work identifies a series of semi-solvents which exhibit varying degrees of PLGA solubility depending on the L:G ratio of the polymer. A good solvent dissolves PLGAs with all L:G ratios ranging from 50:50 to 100:0. A semi-solvent dissolves PLGAs with only certain L:G ratios. Almost all semi-solvents identified in this study increase their PLGA solubility as the L:G ratio increases, i.e., the lactide content increases. This lacto-selectivity, favoring higher L:G ratios, has been applied for separating individual PLGAs in a given depot formulation, leading to analysis of each type of PLGA. This semi-solvent method allows a simple, practical bench-top separation of PLGAs of varying L:G ratios. This method enables isolation and identification of individual PLGAs from a complex mixture that is critical for the quality control of PLGA formulations, as well as reverse engineering for generic products to establish the Q1/Q2 sameness. Keywords: PLGA separation L:G ratio Trelstar Q1/Q2 sameness Long-acting depot”