De‑risking AAV scale‑up: process comparability data from a 50 m² fixed‑bed model

Cell & Gene Therapy Insights 2026; 12(6), 679–690

DOI: 10.18609/CGTI.2026.081

Published: 12 August
Innovator Insight
Dylan Knutson, Xiang Cui, Akash Khorran


Key findings

  • pH, dissolved oxygen, and metabolite profiles were well aligned between the 50 m² and 500 m² fixed‑bed systems across all five runs
  • Bulk harvest titers from the 50 m² system fell within the interquartile range of 500 m² manufacturing batches when scaled by 10×
  • An unplanned shift in transfection conditions may have led to an increase of 48% in bulk harvest titer, identifying a potential avenue for yield improvement not anticipated at the outset of the study

Summary

  • A 50 m² fixed‑bed bioreactor reliably reflected 500 m² manufacturing‑scale behavior across key process parameters
  • The scale‑down approach enabled 3–5 runs per single manufacturing run at significantly lower capital and material cost
  • Specific operational findings – including PID tuning outcomes and a transfection deviation that may have led to a yield increase of 48% – provide practical guidance not available from pre‑study modelling alone

What you will learn

01
How a Quality by Design framework guided scaling strategy and parameter selection across a five-run scale-down study in adherent AAV manufacturing
02
What batch-level data revealed when process parameters were compared between a 50 m² scale-down model and 500 m² manufacturing scale
03
How biomass capacitance enabled real-time detection of a seeding deviation before downstream impact


Q&A highlight

From an MS&T perspective, what was the most valuable aspect of running batches in the 50 m² system?

Key interests
AAV manufacturing Scale-down modelling Fixed-bed bioreactor Process comparability Quality by Design Biomass capacitance Scale-up Upstream processing