Scale‐down of the inactivated polio vaccine production process

Abstract

The anticipated increase in the demand for inactivated polio vaccines resulting from the success in the polio eradication program requires an increase in production capacity and cost price reduction of the current inactivated polio vaccine production processes. Improvement of existing production processes is necessary as the initial process development has been done decades ago. An up-to-date lab-scale version encompassing the legacy inactivated polio vaccine production process was set-up. This lab-scale version should be representative of the large scale, meaning a scale-down model, to allow experiments for process optimization that can be readily applied. Initially the separate unit operations were scaled-down at setpoint. Subsequently, the unit operations were applied successively in a comparative manner to large-scale manufacturing. This allows the assessment of the effects of changes in one unit operation to the consecutive units at small-scale. Challenges in translating large-scale operations to lab-scale are discussed, and the concessions that needed to be made are described. The current scale-down model for cell and virus culture (2.3-L) presents a feasible model with its production scale counterpart (750-L) when operated at setpoint. Also, the current scale-down models for the DSP unit operations clarification, concentration, size exclusion chromatography, ion exchange chromatography, and inactivation are in agreement with the manufacturing scale. The small-scale units can be used separately, as well as sequentially, to study variations and critical product quality attributes in the production process. Finally, it is shown that the scale-down unit operations can be used consecutively to prepare trivalent vaccine at lab-scale with comparable characteristics to the product produced at manufacturing scale.

Next Generation Inactivated Polio Vaccine Manufacturing to Support Post Polio-Eradication Biosafety Goals

“…Virus was harvested, clarified, concentrated, purified, first on size using size exclusion chromatography (SEC) and second by ion exchange chromatography (IEX), and finally inactivated as described previously [13]. …”

“…Virus from the two 350-L (working volume) bioreactors was harvested via a sieve (mesh 75 µm) to obtain a virus harvest free of micro-carriers [13]. Clarification was done using normal flow filtration with a Millipore POD-holder containing C0HC depth filters followed by an Express SHC 0.45/0.22 µm combination filter (Millipore) [3,13] .…”

“…Clarification was done using normal flow filtration with a Millipore POD-holder containing C0HC depth filters followed by an Express SHC 0.45/0.22 µm combination filter (Millipore) [3,13] . Concentration was done by tangential flow filtration using 100 kDa filters [13].…”

“…To support manufacturing and increase the knowledge on IPV manufacturing, efforts like multivariate data analysis and the development of scale-down models, i.e. lab-scale equivalents of the manufacturing-scale processes, have been undertaken [12,13]. The availability of scale-down models, unique in the vaccine world, allows rapid assessment of process changes.…”

Improved poliovirus d-antigen yields by application of different Vero cell cultivation methods

“…The applied production process was based on a scale-down model of the Salk-IPV manufacturing process [3]. 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 [2].…”