As biologics continue to expand in the marketplace, they present a unique array of challenges for producers compared to conventional small molecule drugs. The suite of functional excipients for biologics is limited in comparison to those used in small molecule oral drug delivery, further complicating and limiting the ability to address production challenges. When it comes to biologic liquid dose drugs, recurring issues of stability and processing efficiency are of particular concern.
In response to these industry needs, DuPont Nutrition & Health (DuPont) is currently developing excipients that will provide greater efficiency and stability for biologic formulations than current products. Most recently, DuPont’s research led the business to the development of a new surfactant excipient, FM1000, which is able to better stabilize biologics to interfacial stresses than conventional excipients.
DuPont researchers examined how the new excipient can improve performance in liquid stabilization of protein biologics, which allows them to better understand some of the key causes of protein aggregation. A common challenge with biologic drug processing and in final formulation is limiting the effect of interfacial stress. This stress can be caused by different surfaces throughout manufacture, processing, fill/finish or agitation from shipping and handling. Interfacial stresses can ultimately lead to the denaturation and aggregation of the pharmaceutical, reducing efficacy and presenting other health risks. Surfactants currently added to protect the pharmaceutical are suboptimal and are, at times, susceptible to self-degradation, further limiting efficacy. DuPont researchers explored how to efficiently protect the pharmaceutical from multiple surfaces, allowing the biologic to remain in solution as an active pharmaceutical.
DuPont’s new excipient is able to move to an interface (between the biologic solution and another surface, such as a syringe barrel) and stabilize it 10 to 100 times faster than the equivalent concentration of a more traditional surfactant. This could potentially double or triple the shelf life of biologics. In addition, manufacturers only need to use half of the amount of FM1000 in comparison to other surfactants to obtain similar performance.
“This work highlights the importance of using fundamental science to understand pharmaceutical and pharmaceutical ingredient behavior,” said lead researcher Joshua Katz, PhD, Research Scientist, DuPont Nutrition & Health.
Katz, who joined Dow Chemical's Core Research and Development Formulation Science group in 2011, focuses his research on the development of novel technologies for formulation of non-small molecule pharmaceuticals and biopharmaceutical formulations. Katz partnered with colleagues who contributed their insights and research to the published paper. The full team includes Abigail Nolin, R&D Technologist; Benjamin Yezer, Senior Engineer; and Susan Jordan, Fellow.
“I’m really proud of the diverse team that came together to accomplish this work,” Katz said. “Everyone brought unique skills and perspectives. Abi’s technical skill, Ben’s deep knowledge and passion for fundamental concepts, Sue’s drive to link insights back to customer needs and challenges—all were necessary in realizing research that is not only academically interesting but also valuable to our customers.”
The team’s research began six years ago when Katz and Jordan began to explore some of the limitations with accelerating biologics into the market. One challenge that repeatedly surfaced was the instability and inefficiency of the long-standing industry standard for liquid drug stabilization, Polysorbate 80.
Since then, Katz’s team has been working to identify technologies that are more stable, diverse and dynamic. Their latest research resulted in a published paper in pharmaceutical journal Molecular Pharmaceutics entitled ‘‘Dynamic Properties of Novel Excipient Suggest Mechanism for Improved Performance in Liquid Stabilization of Protein Biologics.” The novel excipient from DuPont could enable new technologies and allow more pharmaceuticals to make the leap from trials to the clinic. Katz’s hope is that the new surfactant excipient will become an industry alternative to Polysorbate 80 to provide easier manufacturing and longer shelf life for biologic drugs.
As DuPont moves forward with FM1000, they will seek to understand its broader use in a variety of formulation conditions and proteins. The team will examine how the excipient reacts to various surfaces and if it retains its efficiency. The surfactant could potentially be used throughout the entirety of the formulation process. As DuPont introduces the excipient into the market place, they will also thoroughly research how well patients tolerate it. Safety is, of course, paramount.
Many biotech companies feel limited by the shortcomings of existing technologies, which means new and potentially life-saving drugs are not being introduced to the market as quickly as they might otherwise. DuPont hopes to embolden formulators by addressing these challenges head-on, harnessing technical knowledge to develop profound solutions. The goal is to introduce technology that improves patient care, lowers potential side-effects and possibly improves the success of the drugs.
“It’s imperative that we utilize our knowledge to design and build next generation technologies for 21st century medicine,” Katz explained. “My passion and commitment as a scientist includes leveraging a strong scientific foundation to engineer the products of tomorrow to cultivate a healthier planet.”