The expiration of patents and other intellectual property rights for originator biological medicines over the next decade opens up opportunities for biosimilars to enter the drug market, and provides affordable biological medicines to patients. However, the development of biosimilars is quite challenging because of the size and complexity of the active substance and nature of the manufacturing process. As mentioned by the FDA earlier this year on the guidance of biosimilar therapeutic products, “the three-dimensional conformation of a protein is an important factor in its biological function… Any differences in higher order structure between a proposed product and a reference product should be evaluated in terms of a potential effect on protein function and stability…”
Hydrogen-deuterium exchange mass spectrometry (HDX-MS) can precisely define tertiary protein structure and, to varying extents, quaternary structure, which could further add to the body of information supporting biosimilarity.
The study presented in this video highlights how HDX-MS can be used to qualify structural attributes of biosimilar mAb drugs. We compared the tertiary structure of Inflectra™, the first biosimilar monoclonal antibody approved in Europe, Korea, and the U.S. against the innovator product, Remicade® (Infliximab). Several batches of innovator product were also analyzed at intact protein and peptide levels in order to gain insight into the conformational difference. The HDX-MS experiments were conducted on an automated HDX platform. Details on the experimental conditions optimized exclusively for these antibodies are discussed. The conformational differences between Remicade and Inflectra are also discussed in detail in this presentation.