The findings and conclusions in this paper are those of the authors and do not necessarily represent the official position of the CDC. “
“Recently, we have produced MK8776 Sabin-IPV (inactivated polio vaccine based on attenuated Sabin strains) clinical lots under cGMP for phase I safety (and indicative immunogenicity) studies in human adults and infants  and . The applied production process was based on a scale-down model of the Salk-IPV
manufacturing process . The use of this scale-down model allowed fast development of a first generation Sabin-IPV, for which the specifications are closely related to that for the regular IPV product . Parallel to this fast-track development an optimization and modernization research program for the manufacturing of Sabin-IPV was started. Examples of modernization are replacement of the used animal derived components (e.g. bovine serum and porcine Libraries trypsin) and antibiotics. These components should preferably be omitted (for the antibiotics primarily to prevent any potential allergic reaction), or respectively replaced by
animal component free (ACF) alternatives to minimize the risk of adverse effects (e.g. the potential transfer of viruses and/or prions). Moreover, a better scientific understanding of the process, resulting in improved process control and ability for troubleshooting, Selleckchem NVP-BGJ398 can be created. Optimization improvements can possibly be found in the currently used, low cell densities (1 × 106 cells mL−1). Assuming comparable virus quality and yields per cell, the use of increased cell densities can potentially result in more efficient use of bioreactor capacity, and ultimately reduce the cost per dose. The demand for IPV is increasing as in 2012 the WHO SAGE group advised all countries to introduce at least one dose IPV in their routine
immunization schedules . With the increased IPV demands, which will further Rolziracetam increase after oral polio vaccine (OPV) cessation, the production capacity will have to increase by scale-up and optimization causing the current IPV price of $ 3.00 per dose to decrease to $ 0.52–$ 1.95 . This is still four to fifteen times the current price of OPV (cost per dose $ 0.14), the vaccine used in most countries. Process optimization for IPV manufacturing will be needed to be able to further reduce manufacturing costs below $ 0.50 to keep polio vaccination economically feasible when switching from OPV to IPV . Here we report initial studies where four different adherent Vero cell cultivation methods were applied using ACF cell culture media: (i) batch, the currently used method for Sabin-IPV preparation; (ii) semi-batch, where daily media refreshments were applied; (iii) perfusion where continuous media refreshment was applied; and (iv) recirculation where media was circulated through the bioreactor and re-used.