Abstract

BIOSIMILARS AS BIOACTIVE MOLECULAR CLONE

Prof. Dr. Dhrubo Jyoti Sen*, Jahangir Nabi, Pooja Raj and Jainik Khamar

Abstract

Biologics are 200 to 1,000 times the size of a small molecule (generic) drug and far more structurally complex. Additionally, biologics and biosimilars are manufactured in living cells, then extracted and purified, whereas small molecule drugs and generics are manufactured purely via chemical synthesis. These fundamental differences in complexity and large-scale manufacturing are at the core of why biosimilars are not equal to generics. Biologics and biosimilars are produced in living cells with a multi-step process. Initially, a basic protein structure is ―translated‖ from a DNA sequence and then modifications, including changes and additions, are made to that basic protein structure. These later changes and additions are called posttranslational modifications. The impact of post-translational modifications on a product is similar to the impact of a farming environment on growing tomatoes. The look and taste of the same type of tomatoes will vary in different farm environments because of the quality of the soil, use of fertilizers, type of irrigation and weather elements like rain, air, sunlight. Similarly, differences in biological systems (e.g., type of living cell with slightly different cellular environments) used to manufacture biosimilars may cause different types and levels of modifications, which in turn may affect the quality, safety or effectiveness of the product. So, whereas a generic can be identical to a small molecule reference product, biosimilars cannot and are not required to be exactly like the biologic reference product. Given the expected differences, regulatory authorities have outlined robust data requirements to demonstrate similarity. Biosimilar manufacturers will generally need to generate data from lab testing, non-clinical testing and clinical testing to show that the biosimilar they have developed will provide the same therapeutic benefit and risks to patients as the reference product.

Keywords: Darbepoetin alfa, Etanercept, Epoetin alfa, Somatropin, Trastuzumab, Adalimumab, Pegfilgrastim, Filgrastim, Infliximab, Rituximab, Bevacizumab, Lispro, Glargine.