Background and aims:
Copaxone ® is a non-biological complex drug (NBCD) for the treatment of multiple sclerosis. Recently, differently manufactured follow-on glatiramoid drug products (FOGAs) purported to be equivalent to Glatiramer acetate (GA, Copaxone ® -Teva) were authorised for marketing in a few countries; including Polimunol (Synthon) in Argentina. To thoroughly compare GA and Polimunol, an array of standard and emerging technologies have been employed.
The present report compares GA and Polimunol using physicochemical and biological methods: amino acid content, molecular weight distribution, circular dichroism, capillary electrophoresis, dynamic light scattering, Coomassie CBBG-250, Viscotek TDAmax, cation exchange chromatograph (CEX), atomic force microscopy (AFM), NanoSight, ion mobility mass spectrometry (IMMS), immunological characterisation and genome-wide expression profiling.
Orthogonal high resolution and multi-dimensional analytical methods revealed significant differences between GA and Polimunol (Table 1). Differences in physical properties were found using Viscotek (intrinsic viscosity, hydrodynamic radius and polydispersity), NanoSight (particle size), and the charge distribution of the polypeptides is different for Polimunol compared to GA as demonstrated by CEX. In AFM images, Polimunol demonstrates globular aggregated shapes whereas GA appears as flat string-like structures. The differences in peptide composition were significantly and independently demonstrated via IMMS. Gene expression differences demonstrated functional relevance of observed differences in physical properties.
The totality of evidence showing differences in physical properties, along with functionally relevant biological disparities highlights the need for adequate and well controlled investigations of Polimunol to ensure the safety and wellbeing of MS patients.