Hamidi, AhdHoeksema, FemkeVelthof, PimLemckert, AngeliqueGillissen, GertLuitjens, AlfredBines, Julie E.Pullagurla, Swathi R.Kumar, PrashantVolkin, David B.Joshi, Sangeeta B.Havenga, MenzoBakker, Wilfried A.M.Yallop, Christopher2021-12-222021-12-222021-04-08Hamidi, A., Hoeksema, F., Velthof, P., Lemckert, A., Gillissen, G., Luitjens, A., Bines, J. E., Pullagurla, S. R., Kumar, P., Volkin, D. B., Joshi, S. B., Havenga, M., Bakker, W., & Yallop, C. (2021). Developing a manufacturing process to deliver a cost effective and stable liquid human rotavirus vaccine. Vaccine, 39(15), 2048–2059. https://doi.org/10.1016/j.vaccine.2021.03.033https://hdl.handle.net/1808/32311Despite solid evidence of the success of rotavirus vaccines in saving children from fatal gastroenteritis, more than 82 million infants worldwide still lack access to a rotavirus vaccine. The main barriers to global rotavirus vaccine coverage include cost, manufacturing capacity and suboptimal efficacy in low- and lower-middle income countries. One vaccine candidate with the potential to address the latter is based on the novel, naturally attenuated RV3 strain of rotavirus, RV3-BB vaccine administered in a birth dose strategy had a vaccine efficacy against severe rotavirus gastroenteritis of 94% at 12 months of age in infants in Indonesia. To further develop this vaccine candidate, a well-documented and low-cost manufacturing process is required. A target fully loaded cost of goods (COGs) of ≤$3.50 per course of three doses was set based on predicted market requirements. COGs modelling was leveraged to develop a process using Vero cells in cell factories reaching high titers, reducing or replacing expensive reagents and shortening process time to maximise output. Stable candidate liquid formulations were developed allowing two-year storage at 2–8 °C. In addition, the formulation potentially renders needless the pretreatment of vaccinees with antacid to ensure adequate gastric acid neutralization for routine oral vaccination. As a result, the formulation allows small volume dosing and reduction of supply chain costs. A dose ranging study is currently underway in Malawi that will inform the final clinical dose required. At a clinical dose of ≤6.3 log10 FFU, the COGs target of ≤$3.50 per three dose course was met. At a clinical dose of 6.5 log10 FFU, the final manufacturing process resulted in a COGs that is substantially lower than the current average market price, 2.44 USD per dose. The manufacturing and formulation processes were transferred to BioFarma in Indonesia to enable future RV3-BB vaccine production.Copyright 2021 Batavia Biosciences BV. Published by Elsevier Ltd. This is an open access article under the CC BY licensehttp://creativecommons.org/licenses/by/4.0/Oral rotavirus vaccineFixed bed bioreactorManufacturing processCost-of-goods modellingStable liquid formulationArticle10.1016/j.vaccine.2021.03.033PMC8062787openAccess