AAV manufacturing: The benefits of growing serum-free, suspension HEK293 cells in the scale-X fixed-bed bioreactor

Meet capacity challenges growing a suspension HEK293 cell line in serum-free conditions to produce an AAV-2 product in high quantities with a scale-X™ fixed-bed bioreactor, thereby providing an alternative to stirred tank reactor technology

Adeno-associated viruses (AAVs) are a vector of choice for a wide range of therapeutic indications. Although early targets were for rare diseases, there is a shift towards higher prevalence indications such as cancers or common neurological disorders. This is combined with the high vector demand per dose sometimes exceeding 1015 vg, which means that manufacturing capacity will increasingly become a bottleneck as the clinical pipeline matures. Industry has taken a stance to address this challenge by developing upstream platforms in suspension adapted HEK293 cell lines in order to benefit from the large capacity offered by stirred tank bioreactors (STRs). However, intensifying and scaling-up STRs is complex, time-consuming can result is delays in the time to market.

Structured fixed-bed bioreactors offer an interesting alternative with a low-shear, well-controlled and homogeneous environment achieving high productivity, high product quality and cost-effectiveness in a reduced footprint for adherent and suspension cells. Univercells Technologies will present how the scale-X™ fixed-bed bioreactor technology is used grow a suspension HEK293 cell line in serum-free conditions to produce an AAV-2 product in high quantities, thereby providing an alternative to stirred tank reactor technology to meet the capacity challenge.

Learning points

  • Understanding the AAV market needs and production challenges
  • The benefits of process intensification and scale-up through biomass immobilization in fixed-bed technology versus stirred tanks for suspension cell lines
  • How cells can be grown at densities 10 to 30 times higher in a structure fixed-bed than in a stirred tank bioreactor while improving product quality and quantity
  • How the scale-X increases cell specific productivity more than 2-fold while decreasing HCP and HC-DNA concentrations resulting in a 24% reduction in cost of goods.

Watch the webinar on-demand

About our experts

Alex Chatel is the Product Manager for viral applications at Univercells Technologies, working on the development of their fixed-bed scale-X™ bioreactor portfolio and integrated downstream processing platform. Prior to this, he held positions as an Enterprise Fellow in technology transfer at University College London and as a Research Engineer at GlaxoSmithKline in Stevenage, UK. Alex earned his Ph.D. in Biochemical Engineering from University College London, UK and his MEng in Chemical Engineering from The University of Manchester, UK.

Laura Siedler is Bioprocess Project Manager in the of Bioprocess & Field Services at Univercells Technologies. Her mission is to support the seamless adoption and establishment of the scale-X systems and the NevoLine Upstream platform as the source of bioprocess efficiency for viral production. Laura acquired 3 years of experience in supporting customers in technology adoption, process optimization and GMP implementation. Laura earned her MS. in Molecular and Applied Biotechnology from the RWTH Aachen University, DE.

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