Jeanne Linke Northrop: How has the antibody molecule pipeline developed in recent years and how do you see the pipeline developing going forward?
Eva Helding: The antibodies are one of the largest classes of biomolecules and there are several approved drugs—the first approved drug was in 1986. The antibodies have been there; however, we have also seen the development of fragments, conjugates, and bispecific antibodies. About 25 percent of the biopharmaceuticals are not pure antibodies they are variants. We have experienced development in the scientific environment where a lot can be done. For example, you are able to engineer the antibodies in newer ways and the biotechnology has also improved. The new type of drugs are engineered to manufacture with a few antibodies—bispecifics have already been approved. Furthermore, we have experienced that FDA has published their guidance for development of this new class of antibodies. I believe everyone is expecting that they will increase in the future.
Jeanne Linke Northrop: How is the development we have seen in the antibody therapeutics area effecting chromatography capture that are used in antibody processing?
Eva Helding: The advantage of producing monoclonal antibodies is that we can apply platform processes which makes the development and manufacturing easy. As we shift to a diverse pipeline this may be difficult to engineer in order to produce. We maintained a good track record of using the protein for capturing the step of bispecific antibodies. It may place more work on the main polishing steps, however, MabSelect may interact with the classes of DH3 in the antibodies—which enables separations targeting the constant DC region. We can see the protein and understand the necessity for having other tools targeting regions on the antibodies such as Kappa ligand or the Lambda ligand. These were developed for fragments and not alkali stable. Furthermore, we have protein which interacts with the Kappa ligand and we have a new engineered version which has recently launched—the MabSelect VL is more alkali stable, which is expected from a chromatography resin for manufacturing. The biopharmaceutical industry is engineering for separation by making the bispecifics a heterogenic one—which is different chains to the pair that you can make a whole construct. If there is electrostatic interaction between chains, it is important to pair them efficiently so impurities are not left out.
Jeanne Linke Northrop:If we look at the polishing steps are there any changing needs due to the increase antibody diversity?
Eva Helding: It is important to work on the polishing steps and to solve the first capture steps, which helps aid the current polishing. The difficulty with the product related impurities is closely related to the target molecules, therefore, you must look at more specific interactions. You may need mixed mode interactions where both iron exchange and pure hydrophobic interactions occur. We have multimodal resin which is good at aggregate removal which targets product related impurities. The HIC resins also demonstrated as good aggregate removers—we have the usual suspects such as aggregates, post end proteins, and tricky wholesome proteins. Polishing may be more challenging and will need improvement as time goes on. We have recently acquired a company for mechanistic modeling, and we are exploring more in-house opportunities. Our customers are looking towards mechanistic and modeling to improve process development—also knowing the process and the mechanistics behind the separation.
Jeanne Linke Northrop:How is Cytiva addressing the changing needs and conditions for purifying antibody fragments and bispecific antibodies?
Eva Helding: I believe we are trying to address the challenges from different angles. It is crucial to think about the resins or protocols which we are aiming for to provide tools from research to manufacturing. We should have scale processes and we need resins which can be scaled and packed in all sizes of the columns. I believe we have an intense program on trying to address all the different aspects to receive good purity of the future drugs. The full process of an interaction depends on the amount of water consumed in terms of a separation. It may be beneficial to reuse a resin for many cycles.