June 6-11, 2010
Tuberculosis is the world’s second deadliest infectious disease, with over 9 million new cases diagnosed in 2006. In collaboration with the Aeras Global Tuberculosis Vaccine Foundation, we are developing a recombinant tuberculosis adenovirus based vaccine (rAd35). Currently a series of three Phase I trials are taking place, with the first two studies indicating very promising results, safety and toleration. In November 2008 we started a Phase II study in South Africa. The manufacturing process supporting these clinical studies was developed using the PER.C6® cell substrate. With the productivity of this production process, scale-up to 10,000-liter bioreactor will be required to assure an immediate global impact on disease burden immediately after licensure. Given the uncertainties attendant to the CAPEX commitment required to develop a facility for a 10,000-liter bioreactor process and the unprecedented need to develop a viral vaccine manufacturing process at 10,000L scale under BSL 2 conditions, our approach is to focus on intensification of the rAd35 manufacturing process. The process intensification strategy is a combined effort of upstream, downstream and analytical development. We have set the following objectives: 1- A 10-fold increase in volumetric productivity of the upstream process 2- A downstream process that can accommodate this process without compromise to purity of the non-intensified process 3- Fit the intensified process in Crucell’s existing production facilities by application of single use technologies 4- A safe, effective vaccine available at reasonable costs This presentation will highlight our progress in upstream development of our intensified rAd35 process. We will show a 10-fold intensification at bench scale. Furthermore, for the first time our scale-up activities will be presented. We will show the results of the upstream process in 50L single-use bioreactors and the impact on cost of goods for this intensified process at production scale.
Alfred Luitjens and Herman van Herk, "SCALE-UP OF AN INTENSIFIED PROCESS FOR RAD35 ADENOVIRUS PRODUCTION USING THE PER.C6® CELL SUBSTRATE" in "Vaccine Technology III", John G. Auniņš,Merck, USA; Barry C. Buckland, BiologicB, USA; Kathrin U. Jansen, Pfizer, USA; Paula Marques Alves, IBET, Portugal Eds, ECI Symposium Series, (2010). http://dc.engconfintl.org/vaccine_iii/15