Seed train in cell culture: foundation of scalable biomanufacturing

In CGT and biologics manufacturing, effective seed train cell culture is essential - but current methods slow down scalability.

The seed train: a stepwise expansion of cells. From vial or isolated cells through intermediate stages, cells are cultivated to generate the biomass needed for production-scale bioreactors.

What is a seed train in cell culture

In cell culture-based biomanufacturing, a seed train refers to the stepwise process of expanding a small number of cells into the large biomass required for production-scale bioreactors. Whether starting from a cryopreserved vial or freshly isolated cells, the seed train builds up sufficient healthy and viable cells for inoculating the final production vessel.

This multi-stage process is essential across a variety of applications—including biologics production, vaccine manufacturing, and cell and gene therapy (CGT). Each expansion step must maintain cell quality, minimize contamination risk, and ensure reproducibility. The efficiency and reliability of a seed train cell culture system directly affect downstream yield and product consistency.

Where seed trains matter most: Biologics, vaccines and cell therapy

In biologics manufacturing, seed trains are used to amplify production cell lines such as CHO or HEK cells to volumes needed for protein or antibody production. For vaccine production, they provide the necessary biomass for virus propagation in either adherent or suspension platforms.

In CGT manufacturing, seed trains take on an even more delicate role. Often starting from very limited patient- or donor-derived cells, the expansion process must preserve critical phenotypic and functional characteristics. Moreover, timelines are tight—especially for autologous therapies—making process reliability essential.

Common practices in seed train bioreactor scale-up

Today, seed trains typically progress through a series of vessel formats:

• T-flasks or spinner flasks for initial recovery and adaptation

• Roller bottles or multi-layer flasks for expansion

• Stirred-tank bioreactors (1–10 L, then up to 200 L) for scaling to production

  
  

Most seed train bioreactor workflows involve manual handling, multiple open steps, and a significant cleanroom footprint. Each step introduces risk of contamination or inconsistency, especially when transferring between formats. This complexity also increases training requirements and operational costs.

Limitations of conventional seed train systems

Despite being the industry standard, traditional seed train systems present notable challenges:

• Labor-intensive: Multiple vessels require monitoring, handling, and transfer

• Space-demanding: Incubator and cleanroom capacity can quickly become limiting

• Scale-out dependence: Expanding via more vessels instead of true scale-up

• Process variability: Different vessel types may expose cells to inconsistent shear, oxygenation, and surface conditions

• CGT-specific sensitivity: Patient-derived cells often struggle to adapt in high-shear or unfamiliar environments

  
  

These issues can slow down manufacturing timelines, increase batch-to-batch variability, and make tech transfer between sites more complex.

A smarter seed train: Compact bioreactor innovation

To overcome these hurdles, Green Elephant Biotech offers a compact, space-efficient bioreactor that streamlines the seed train process. Designed specifically for adherent cell expansion, the CellScrew® system delivers the advantages of 2D cultivation—optimal cell harvesting, low shear stress, and surface familiarity—with the scalability and efficiency of a 3D-like system.

• Reduced footprint: High surface-to-volume ratio enables compact scalability

• Process consistency: Maintains uniform culture conditions from seed to scale

• Ease of use: Simplifies workflows with fewer vessels and fewer handling steps

  
  

This makes it an ideal fit for bridging the gap between early cell expansion and production scale—especially in CGT environments, where time, cell quality, and reproducibility are mission-critical.

As cell-based therapies and biologics production continue to expand, the seed train remains a foundational part of any bioprocess. But to keep pace with modern demands, manufacturers need systems that minimize manual work, reduce risk, and offer predictable scalability.