Biosimilar Evaluation and Structural Characterization, A Comparison Study for Enoxaparin

Generic forms of chemically- synthesized drugs must exhibit chemical identity and be bioequivalent in healthy human subjects. Biologic products are 100- to 1,000-fold larger than chemically synthesized drugs, with sophisticated three-dimensional structures, and can be mixtures of isoforms rather than pure homogeneous entities. Therefore, the development process for biosimilars is more complex than for a true generic and the demonstration of approvability for biosimilars differs from the standard generics approach as it is based on a comparability exercise rather than on demonstration of bioequivalence. This study examines the case of a Low-molecular-weight heparins (LMWHs): enoxaparin which is among smallest biological molecules. Different chemical tests such as Nuclear Magnetic Resonance (NMR), Size exclusion Chromatography, Specific absorbance, stability tests and biological assay (anti-factor Xa activity and anti-factor II a activity) were used for a comparability exercise focusing on quality and structural aspects of enoxaparin biosimilar product compared to the reference product. All tests and comparative studies showed no significant difference. in fact the data observed suggests comparable results even under accelerated conditions of stability study. This study suggests that there is no significant difference in the profile structure and overall studied quality aspects of the reference product compared to the similar biological medicinal product. however specific analytical methods as well as additional biological and pharmacological tests may be used to address their interchangeability.