Glatiramoids are non-biologic complex drugs (NBCDs) comprising four naturally occurring amino acids in a complex copolymeric mixture. The first and most thoroughly studied glatiramoid, glatiramer acetate (Copaxone®, Teva Pharmaceutical Industries, Ltd.) is approved for treatment of relapsing-remitting forms of multiple sclerosis, an autoimmune disorder characterized by neuroinflammation and progressive neurodegeneration. Glatiramoid mixtures comprise a potentially incalculable number of structurally closely related active peptide moieties that cannot be isolated, quantified, or identified using even the most sophisticated available multidimensional separation techniques. Numerous studies have demonstrated that the glatiramer acetate in Copaxone® modulates innate and adaptive immune cell responses to promote antiinflammatory and neuroprotective activities; however, the active epitopes in Copaxone® are unknown and the precise mechanisms of immunomodulatory activity responsible for its therapeutic efficacy are not entirely elucidated. The identity, quality, and consistency of a glatiramoid are inexorably linked to its own manufacturing process. Several manufacturers now market glatiramoids in various countries that are purported to be generic or follow-on versions of Copaxone®; at this writing, no full set of peer-reviewed long term safety and efficacy data for these products is available in the medical literature. Sophisticated analysis techniques, though unable to completely characterize glatiramoid mixtures can differentiate among them based on physicochemical features and biological activities. Comparative gene expression studies have demonstrated important differences between the reference drug (Copaxone®) and purported generic glatiramer acetate products that may have significant implications for the safety and efficacy of the purported generic products. Currently, there is no globally agreed defined pathway for regulatory approval of follow-on and generic glatiramoid products. In the interest of patient safety and well-being, there is an urgent need for regulatory agencies to come to consensus regarding criteria needed to establish therapeutic equivalence among members of the glatiramoid class. Scientific approaches discussed in this chapter may be helpful when evaluating glatiramoid formulations in the framework of equivalence testing.