A Review of the Non-clinical and Clinical Requirements for the performance of a comparability exercise for Bevacizumab biosimilars

The development of monoclonal antibodies (mAbs) in recent decades has enhanced the therapeutic options available to clinicians for the treatment of several diseases such as cancer, autoimmune disorders, and several others. Monoclonal antibodies are produced through the use of different biotechnological techniques and rely on living systems as platforms for their production. Accordingly, mAbs are large proteins with complex three-dimensional structures and each production platform is unique for each mAb and producing exact copies of each mAb is nearly impossible. With several mAbs losing their patency in the previous two decades, many pharmaceutical companies are pursuing the production of generic mAbs, or what is known as biosimilars. The originator Bevacizumab has lost its patency in 2019 allowing several pharmaceutical companies to introduce into the clinic several Bevaciumab copies with varying degrees of quality with some being inferior to the originator Bevacizumab in what is known as intended copies. These agents and due to the lack of the totality of evidence for their comparability exercise needed versus the originator Bevacizumab could expose patients receiving these medications to several risks including lack of efficacy, immunogenicity, and potential toxicity. This review aims to provide pharmaceutical personnel working on the development and commercialization of Bevacizumab biosimilars in addition to regulatory officers worldwide responsible for the regulatory review of bevacizumab application dossiers with the minimal technical requirements required to perform a full comparability exercise between any bevacizumab biosimilar and its reference product. It will build on the EMA and U.S. FDA guidelines and the current literature to provide a comprehensive analysis of the various aspects of the bevacizumab comparability exercise and ensure that the product is of similar quality to the reference biologic.