Demonstration of Biological and Immunological Equivalence of a Generic Glatiramer Acetate

BACKGROUND: In April 2015, the US Food and Drug Administration approved the first generic glatiramer acetate, Glatopa® (M356), as fully substitutable for Copaxone® 20 mg/mL for relapsing forms of multiple sclerosis (MS). This approval was accomplished through an Abbreviated New Drug Applica-tion that demonstrated equivalence to Copaxone. METHOD: This article will provide an overview of the methods used to establish the biological and immu-nological equivalence of the two glatiramer acetate products, including methods evaluating antigen-presenting cell (APC) biology, T-cell biology, and other immunomodulatory effects. RESULTS: In vitro and in vivo experiments from multiple redundant orthogonal assays within four biologi-cal processes (aggregate biology, APC biology, T-cell biology, and B-cell biology) modulated by glati-ramer acetate in MS established the biological and immunological equivalence of Glatopa and Copaxone and are described. The following were observed when comparing Glatopa and Copaxone in these exper-iments: equivalent delays in symptom onset and reductions in “disease” intensity in experimental autoim-mune encephalomyelitis; equivalent dose-dependent increases in Glatopa- and Copaxone-induced mono-kine-induced interferon-gamma release from THP-1 cells; a shift to a T helper 2 phenotype resulting in the secretion of interleukin (IL)-4 and downregulation of IL-17 release; no differences in immunogenicity and the presence of equivalent “immunofingerprints” between both versions of glatiramer acetate; and no stimulation of histamine release with either glatiramer acetate in basophilic leukemia 2H3 cell lines. CONCLUSION: In summary, this comprehensive approach across different biological and immunological pathways modulated by glatiramer acetate consistently supported the biological and immunological equiv-alence of Glatopa and Copaxone.