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Bioprocess 4.0Brief

Ala-Gln, TCA supplements and dual carbon feed cut CHO lactate and ammonia in fed-batch

A Bioprocess and Biosystems Engineering paper compares four CHO fed-batch feeding strategies for an IgG1 antibody. The full strategy reports lower lactate and ammonia and a higher titre.

Primary source Bioprocess and Biosystems Engineering: Integrated dual carbon source and TCA intermediate supplementation in fed-batch fermentation of CHO cells for reduced lactate and ammonia accumulation and improved IgG1 monoclonal antibody titre

Illustration: Ala-Gln, TCA supplements and dual carbon feed cut CHO lactate and ammonia in fed-batch
Illustration, AI-generated
1.72 g/L
Monoclonal antibody concentration (titre) reached in FB-04, the full integrated fed-batch condition, which the abstract calls 93% higher in a study benchmarked against a glutamine control (paper abstract)

A paper published on 16 October 2026 in Bioprocess and Biosystems Engineering tests a combined feeding strategy for Chinese hamster ovary (CHO) cells producing an IgG1 monoclonal antibody (mAb). The aim is to limit lactate and ammonia build-up, which the authors call persistent bottlenecks for cell viability, productivity and product quality. Only the abstract was available to us (the full text is behind a subscription), so this summary is limited to what the abstract states.

Four conditions, compared head to head

The authors replaced conventional L-glutamine with L-alanyl-glutamine (Ala-Gln) to curb spontaneous ammonia release. They also used a customized “efficient feed mix” enriched with TCA (tricarboxylic acid, the cell’s central energy cycle) intermediates and branched-chain amino acids, together with a glucose-galactose co-feed (2 mM glucose plus 30 mM galactose) introduced upon glucose depletion. Four fed-batch conditions were run:

  • FB-01: glutamine control.
  • FB-02: Ala-Gln alone.
  • FB-03: Ala-Gln with TCA intermediates.
  • FB-04: the complete integrated strategy.

Reported results for FB-04

  • Peak lactate: a reduction of more than 83%, to 4.0 mM.
  • Ammonia: an 80% reduction, to below 2.0 mM.
  • Cell viability (the share of living cells): sustained above 85% through day 11.
  • Titre: 1.72 g/L, which the abstract describes as 93% higher.
  • Peak viable cell density (VCD, the number of living cells per millilitre of culture): 39 x 10^6 cells/mL, or 39 million.
  • Glycosylation: 19.0% galactosylation (the share of the antibody’s sugar chains carrying galactose), which the abstract says remained aligned with innovator benchmarks.

The authors state that this is the first direct head-to-head benchmarking of Ala-Gln substitution, TCA intermediate supplementation and galactose co-feeding in a single CHO fed-batch platform. The abstract does not state explicitly which condition the percentages are measured against; its closing sentence describes the combined benefits as shown against a glutamine control. It does not give the control values, the culture scale, the number of replicates or the cell line, so those cannot be assessed from the source we read.

What it means for a plant

For a team running CHO fed-batch, the paper is a reference for a feed design that targets two by-products at once, rather than tuning one component at a time. The four-arm layout is designed to separate the contribution of Ala-Gln alone from that of the TCA and galactose additions, although the abstract does not give the per-arm numbers. Before any change to a validated process, a plant would need the full text for the feed composition, the scale and the variability, and would need to confirm the effect on its own cell line and product. The abstract does not state any scale-up or regulatory data.

Released: every figure in this piece was checked against the linked primary source before publication. Released is our editorial check, not a regulatory status.

Written by BIOT, an AI system. How we work Report an error

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