June 17-22, 2018
In 2014, West Africa experienced the worst outbreak of Ebola virus in history with 10 times more cases than in all previous outbreaks combined. In response to this public health emergency, MSD and a global network of partners collaborated to speed the research, development, and deployment of a candidate vaccine that ultimately provided the first evidence of efficacy in human subjects for any Ebola vaccine. While work continues to ultimately license the candidate vaccine, a risk-based approach to process development and characterization was used to accelerate and prioritize the study of parameters. Risk was evaluated by experts familiar with unit operations and parameters in similar licensed live viral vaccines and resulted in an overall plan of study encompassing five major areas – cell expansion, viral infection, purification, formulation, and general robustness. In parallel to batch size scale-up to support commercial production, a scale-down model comparable to commercial scale production was developed and enabled high-throughput experimentation. This approach reduced experiment cycle time from eight weeks to three weeks, reduced process volumes enabling design of experiments, and resulted in high-throughput execution of lab-scale studies. Typically, potency is extremely sensitive to multiplicity of infection (MOI); this vaccine is capable of producing acceptable potencies during viral infection with a 1000x range of MOIs. The most critical parameter during purification is digestion, which results in a ~10-fold increase in product potency. The final tangential flow filtration unit operation is extremely robust with no critical process parameters while still being capable of effectively clearing residual enzyme. Additionally, the implementation of a fully disposable single-use drug substance manufacturing process also helped accelerate process development and characterization activities. Component user requirements and schematic drawings were used to design prototypes which were evaluated using innovative shake-down studies. This approach resulted in a rugged system of end-to-end, single-use disposable components with 42 modular, “plug-and-play” designs available to support >500 single-use assemblies needed in production. Components were delivered to the commercial manufacturing site within 15 months with no required design changes following water-run testing. Taken together these approaches helped accelerate process development and characterization studies that will expedite the licensure of an Ebola virus vaccine.
Randi Saunders, Joseph P Califano, Dusan Ruzic, and Kristin Valente, "A vaccine for Ebola virus – approaches and results of accelerated process development and characterization studies" in "Vaccine Technology VII", Amine Kamen, McGill University Tarit Mukhopadhyay, University College London Nathalie Garcon, Bioaster Charles Lutsch, Sanofi Pasteur Eds, ECI Symposium Series, (2018). http://dc.engconfintl.org/vt_vii/103