comparability

The term biosimilar is used for a subsequently launched version of a biologic product which is similar in terms of quality, safety, and efficacy to an already licensed “Reference Biologic” product. The primary purpose of biosimilars is to reduce the healthcare costs associated with the use of biologics and thereby increase access to healthcare. Unlike small molecule generics, the bioequivalence approach is not considered appropriate for the approval of biosimilars. The approval of biosimilars is based on a stepwise comparability exercise with the “Reference Biologic”, starting with a comprehensive physicochemical and biological characterization. The extent and nature of the required nonclinical in vivo studies and clinical studies depend on the level of evidence obtained from the previous steps. Regulations require that the “Reference Biologic” should have been licensed/approved in the same country/region or in other ICH countries based on a full registration dossier. Apart from the comparability exercise, regulations also deal with indication extrapolation, pharmacovigilance, and substitution and interchangeability. This chapter also briefly describes the considerations for exclusivity, market access, and commercialization of biosimilars.

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.