Same Product Different Regulatory Approach Around the World: Glatiramer Acetate

Abstract

Complex drugs may be either biological, if the active ingredients are derived from a biological source, or non-biological, if obtained by chemical synthesis. In both cases, their quality depends considerably on the manufacturing process. For Non Biological Complex Drugs (NBCDs), in particular, complexity may arise either from the active substance, as in the case of glatiramer acetate (GA), or from other sources, such as the formulation, as in the case of liposomes (Figure 1) (1). GA is approved, in the US and the EU, as a diseasemodifying treatment for patients with relapsing forms of Multiple Sclerosis. It is a heterogeneous mixture of not fully characterized synthetic polypeptides, containing L-alanine, L-lysine, L-glutamic acid, L-tyrosine in the constant molar ratio 0.43:0.34:0.14:0.09, with and average molecular weight from 5 to 9 kDa and distribution range from 2.5 to 20 kDa (2). The amino acid sequences are not completely random, being the result of both the physicochemical properties of the starting materials and the fundamental reaction scheme. However, they are not completely conserved from batch to batch, even when the process is tightly controlled. Indeed along with conserved characteristics such as amino acid molar ratio other characteristics such as the specific amino acid sequences will show batch-to-batch variability (1). To address this complexity, for the marketing of GA copies, US and EU regulatory agencies have chosen a generic approach integrated with additional data. However, the implementation is different in the two jurisdictions (Figure 1).