The excipient used in the formulation of a biologic is an important factor in drug processing and, when it goes wrong, it can cost pharmaceutical companies millions of dollars.
With biologics being a growing market, this has seen more companies become involved in developing excipients for the space, such as Roquette’s increased investment that saw them step into the space in 2017.
DuPont is also working in the space, developing new excipients that could provide greater efficiency and stability for existing and pipeline products.
Joshua Katz (JK), a research scientist at DuPont, spoke to BioPharma-Reporter (BPR) about newly developed FM1000 – a surfactant that Katz suggests could double to triple the shelf life of biologics.
BPR: Could you broadly outline the work DuPont carries out developing excipients?
JK: We have been working for a while on trying to develop new materials that will improve the stability of biologic pharmaceuticals when they come into contact with various surfaces. There are excipients added that protect the pharmaceutical from these surfaces. We are interested in developing better excipients that will do a better job of getting to that surface and allowing the biologic to stay in solution, in its native state, therefore as an active pharmaceutical.
BPR: Why is there a need for newly developed excipients?
JK: On the biologics side, the common problems you see is that as the formulation is agitated and is exposed to various shear stresses then it has the ability to interact with these surfaces, which will lead to denaturation and aggregation of the pharmaceutical. What is typically used to address this is a formulation around the pharmaceutical, with various surfactant added at small levels to compete with the pharmaceutical at those surfaces.
However, the surfactants themselves also have several different problems and the one issue that we went after is that they are often not very efficient – they aren't good enough at competing with the biologic at the surfaces. You also see issues with surfactants that aren't stable enough by themselves, they're subject to hydrolysis and residual enzymes that are produced as part of the manufacturing of the pharmaceutical, which can degrade the surfactant.
We've developed a surfactant that is more efficient, which is what our publication focused on. It is also more stable than the currently available technologies.
BPR: In what way is the excipient DuPont has developed more efficient and stable?
JK: The surfactant we have developed, FM1000, is able to get to an interface and stabilise it; this would be the interface between the solution that contains the biologic and either an air pocket or the wall of a syringe. It is able to get to that interface between 10 and 100 times faster than the equivalent concentration of your state-of-the-art incumbent surfactant.
That's one part of the efficiency and that translates into improved stabilisation – our work with model pharmaceuticals shows you can use about half of the amount of surfactant, FM1000, compared to the next best technology. Alternatively, you could double to triple the shelf life of the biologic with an equivalent concentration of excipient.
BPR: What is the next step for FM1000?
JK: We're looking to understand more broadly its potential use, with different types of proteins and under different formulation conditions. We are also looking at its potential use through the entire development of biologics all the way along to the packaging, shipping and delivering to patient’s stage. We're interested in looking at FM1000 with different surfaces – all of the surfaces a biologic might see, to answer whether it remains as efficient. We're also trying to look at toxicology, to make sure that, as we bring this excipient to market, it is well tolerated by patients.
BPR: As the biologics market develops, is the need to develop such technologies growing in importance?
JK: I think it's about enabling new technologies. Right now, the biotech companies out there are developing new modalities and they're having a lot of challenges with formulations because existing technologies are not sufficient to bring new drugs to market.
If we have a new technology that is more efficient that addresses these challenges then it will be enabling for new classes of pharmaceuticals to be brought to market to improve patient care and lower the number of side-effects, potentially even improving the efficacy of the treatments themselves. That's where we're going to see a lot of value brought, with more pipeline pharmaceuticals potentially successfully brought through to the clinic for our customers.
Joshua Katz joined Dow Chemical's Core R&D Formulation Science group in 2011, focusing his research on the development of novel technologies for formulation of non-small molecule pharmaceuticals and biopharmaceutical formulations. Prior to joining Dow, he received his undergraduate degree in chemistry from MIT and a Ph.D. in bioengineering from the University of Pennsylvania.