Sabin inactivated polio vaccine upstream process development using fixed-bed bioreactor technology

Vaccine, vol. 53, pp. 126950

Abstract

Eradication of polio disease remains a challenge for countries with limited health-care infrastructure. Regional vaccine production is expected to secure a sustainable and equitable availability of vaccines supporting the polio eradication end-game. Regional manufacturing of Inactivated Polio Vaccines based on the attenuated Sabin strains and using an isolator-based contained micro-facility is expected to avoid any potential risk of shortage of polio vaccines in the future, ensure equitable access to sufficient doses of IPV while securing a safe manufacturing environment. However, polio vaccine production requires biosafety level 3 containment and is complicated by the restrictions imposed from the adherent nature of the virus-producing Vero cell line. To overcome these issues that have hampered regional polio vaccine production so far, at Batavia Biosciences we developed an inactivated polio vaccine production process based on the polio Sabin strains in a contained microfacility. By incorporating a tangential flow filter coupled to a fixed-bed bioreactor with a large attachment surface area (150 m 2 ), we could increase process efficiency and reduce the production footprint allowing for regional demand-driven production. The reduced square meters of the manufacturing site that handles the live virus were achieved by integrating the fixed-bed bioreactor with the concentration step (TFF). The increased efficiency was realized by using less resources, fully disposable virus production, and a down- and up-scalable process depending on vaccine demand. The here-developed scalable production process with reduced production footprint is considered a useful and cost-effective method for regional vaccine production, for example in pandemic preparedness efforts to efficiently contain virus outbreaks. • Poliovirus vaccine production is feasible using a low-footprint container-sized production site. • Structured fixed-bed bioreactors enable linear upscaling of Vero cell growth and virus production. • A tangential flow filter coupled to a fixed-bed bioreactor increased process efficiency and reduced the production footprint. • The developed scalable production process is considered a useful and cost-effective method for regional vaccine production. • Regional isolator-based sIPV manufacturing is expected to ensure equitable access to sufficient doses of IPV.

Authors 11

1. Ahd Hamidi Aachen Batavia Biosciences B.V

   Batavia Biosciences (Netherlands)

   Affiliation as printed

   Batavia Biosciences B.V., Bioscience Park Leiden, Zernikedreef 16, 2333CL, Leiden, the Netherlands

2. Marieke Willemsen Aachen Batavia Biosciences B.V

   Batavia Biosciences (Netherlands)

   Affiliation as printed

   Batavia Biosciences B.V., Bioscience Park Leiden, Zernikedreef 16, 2333CL, Leiden, the Netherlands

3. Jean‐Christophe Drugmand

   Univercells (Belgium)

   Affiliation as printed

   Univercells Technologies SA, Chemin De la Vieille Cour 56a, 1400 Nivellles, Belgium

4. Mónika Z. Ballmann Aachen Batavia Biosciences B.V

   Batavia Biosciences (Netherlands)

   Affiliation as printed

   Batavia Biosciences B.V., Bioscience Park Leiden, Zernikedreef 16, 2333CL, Leiden, the Netherlands

5. Pim Velthof Aachen Batavia Biosciences B.V

   Batavia Biosciences (Netherlands)

   Affiliation as printed

   Batavia Biosciences B.V., Bioscience Park Leiden, Zernikedreef 16, 2333CL, Leiden, the Netherlands

6. Hans Verdurmen Aachen Batavia Biosciences B.V

   Batavia Biosciences (Netherlands)

   Affiliation as printed

   Batavia Biosciences B.V., Bioscience Park Leiden, Zernikedreef 16, 2333CL, Leiden, the Netherlands

7. Jochem Pronk Aachen Batavia Biosciences B.V

   Batavia Biosciences (Netherlands)

   Affiliation as printed

   Batavia Biosciences B.V., Bioscience Park Leiden, Zernikedreef 16, 2333CL, Leiden, the Netherlands

8. Laura Palladino Aachen Batavia Biosciences B.V

   Batavia Biosciences (Netherlands)

   Affiliation as printed

   Batavia Biosciences B.V., Bioscience Park Leiden, Zernikedreef 16, 2333CL, Leiden, the Netherlands

9. Menzo J E Havenga Aachen Batavia Biosciences B.V

   Batavia Biosciences (Netherlands)

   Affiliation as printed

   Batavia Biosciences B.V., Bioscience Park Leiden, Zernikedreef 16, 2333CL, Leiden, the Netherlands

10. Chris Yallop Aachen Batavia Biosciences B.V

    Batavia Biosciences (Netherlands)

    Affiliation as printed

    Batavia Biosciences B.V., Bioscience Park Leiden, Zernikedreef 16, 2333CL, Leiden, the Netherlands

11. Wilfried A.M. Bakker corresponding Aachen Batavia Biosciences B.V

    Batavia Biosciences (Netherlands)

    Affiliation as printed

    Batavia Biosciences B.V., Bioscience Park Leiden, Zernikedreef 16, 2333CL, Leiden, the Netherlands. Electronic address: w.bakker@bataviabiosciences.com