TECHNICAL GUIDANCE ON THE PHYSICOCHEMICAL AND FUNCTIONAL COMPARABILITY EXERCISE FOR TRASTUZUMAB BIOSIMILARS

Abstract

The introduction of monoclonal antibodies (mAbs) into the field of oncology has revolutionized the treatment options available to clinicians for the treatment of several malignancies. Unlike their classical small molecule drug counterparts, mAbs are large complex biological molecules that are generated using recombinant engineering and produced through the use of living systems. The high complexity of these agents, combined with the complexity of their manufacturing process, poses significant challenges for the pharmaceutical industry in producing exact copies of the originator molecules. With several mAbs losing their patency in recent years, several pharmaceutical manufacturers are pursuing the development of mAb copies or what is known as biosimilars as generic copies to the originator mAbs. Developing a mAb biosimilar requires that the manufacturer performs an extensive comparability exercise between the originator mAb and its biosimilar to provide evidence that the biological copy is similar to the originator in regards to physicochemical and functional properties, non-clinical pharmacodynamics and immunogenicity, and finally, clinical trials to ensure the safety and efficacy of the biological molecule. The inability to perform a high-quality similarity exercise could generate inferior biological copies or what is known as intended copies. Trastuzumab is a humanized mAb that was designed to target HER 2 receptors which are highly expressed in a variety of tumors, including 25-30% of invasive breast carcinomas. The aim of this review is to provide technical guidance regarding the physicochemical and functional similarity exercise for pharmaceutical personnel working in the research and development of Trastuzumab biosimilars in addition to regulatory officer’s worldwide reviewing biosimilars dossiers within public health authorities. This data will provide valuable information in detailing the main quality parameters needed to demonstrate the analytical similarity of any Trastuzumab biosimilar to its reference product.