The manufacturing considerations of bispecific antibodies

Antibody therapies have made huge strides in providing safe and efficacious drugs for autoimmune, cancer, and infectious diseases. These bispecific antibodies can be assembled from the basic building blocks of IgGs, resulting in dozens of formats.

It is important to consider the manufacturability of these formats early in the antibody discovery phases. Broadly categorizing bispecific antibodies into IgG-like, fragment-based, appended, and hybrid formats can help in looking at early manufacturability considerations.

Ideally, bispecific antibody manufacturing should contain a minimal number of steps, with processes that give high yields of protein with no contaminants. Many of these have been determined for the fragment-based bispecific blinatumomab and the IgG-like bispecifics from hybridomas. However, for new formats, these need to be considered early in the research and development pipeline. The hybrid formats offer an unusual alternative in generating high pure yields of bispecific molecules if the engineering challenges can be deciphered.