title: Demonstration of Biological and Immunological Equivalence of a Generic Glatiramer Acetate.
abstract: 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 Application that demonstrated equivalence to Copaxone.
  
  
  METHODS
  This article will provide an overview of the methods used to establish the biological and immunological equivalence of the two glatiramer acetate products, including methods evaluating antigenpresenting cell (APC) biology, T-cell biology, and other immunomodulatory effects.
  
  
  RESULTS
  In vitro and in vivo experiments from multiple redundant orthogonal assays within four biological processes (aggregate biology, APC biology, T-cell biology, and B-cell biology) modulated by glatiramer 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 experiments: equivalent delays in symptom onset and reductions in "disease" intensity in experimental autoimmune encephalomyelitis; equivalent dose-dependent increases in Glatopa- and Copaxone- induced monokine-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.
  
  
  CONCLUSIONS
  In summary, this comprehensive approach across different biological and immunological pathways modulated by glatiramer acetate consistently supported the biological and immunological equivalence of Glatopa and Copaxone.
authors.affiliation: Research Department, Momenta Pharmaceuticals, Inc., Cambridge, MA. United States.
authors.forename: Josephine
authors.initials: J
authors.lastname: D Alessandro
authors.affiliation: Research Department, Momenta Pharmaceuticals, Inc., Cambridge, MA. United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Garofalo
authors.affiliation: Division of Bioequivalence I, Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD. United States.
authors.forename: Ganlin
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Research Department, Momenta Pharmaceuticals, Inc., Cambridge, MA. United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: Honan
authors.affiliation: Research Department, Momenta Pharmaceuticals, Inc., Cambridge, MA. United States.
authors.forename: Jay
authors.initials: J
authors.lastname: Duffner
authors.affiliation: Research Department, Momenta Pharmaceuticals, Inc., Cambridge, MA. United States.
authors.forename: Ishan
authors.initials: I
authors.lastname: Capila
authors.affiliation: Research Department, Momenta Pharmaceuticals, Inc., Cambridge, MA. United States.
authors.forename: Ian
authors.initials: I
authors.lastname: Fier
authors.affiliation: Research Department, Momenta Pharmaceuticals, Inc., Cambridge, MA. United States.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Kaundinya
authors.affiliation: Division of Neurology, Florida Atlantic University, Boca Raton, FL. United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kantor
authors.affiliation: Momenta Pharmaceuticals, Inc., 675 West Kendall Street, Cambridge, MA 02142. United States.
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Ganguly
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D000068717:Glatiramer Acetate / Q000627:therapeutic use*; D006632:Histamine / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000633:toxicity; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D010446:Peptide Fragments / Q000633:toxicity; D013601:T-Lymphocytes / Q000187:drug effects; D013810:Therapeutic Equivalency
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D018991:Myelin Proteolipid Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); C435023:myelin proteolipid protein (139-151); D000068717:Glatiramer Acetate; D006632:Histamine
keywords: Antigen-presenting cell; B cell; T cell; generic; glatiramer acetate; multiple sclerosis