Scale Up or Scale Out? Choosing an Adherent Cell Culture Platform

Selecting an adherent cell culture platform requires understanding how scale-up and scale-out strategies affect space utilization, labor demands, investment, and sustainability. This article compares roller bottle–based scale-out workflows with cell factory–based scale-up approaches to support informed platform selection for vaccine manufacturing.

Navigating Scale Decisions in Vaccine Manufacturing

With the growing demand for animal and human vaccines, expanding adherent cell culture production facilities can be complicated.

Efficiently transferring technology to CDMO partners can add complexity while alternatively, expanding capacity within existing or newly constructed spaces can require substantial investment. For instance, space costs can range from $500 to $1,000 per square foot (1). Additionally, logistical planning can take 12-18 months, from initial design to operational readiness (2).

Choosing the right adherent cell culture platform for vaccine production is crucial for scalability, cost-effectiveness, ease of use, and productivity. Two commonly used platforms are roller bottles and cell factory systems. Roller bottles, well-suited for scale-out, are often valued for their low cost, familiarity, and ease of transfer. In comparison, cell factory systems, designed for scale-up, provide user-friendliness, space efficiency, and the added advantage of reduced contamination risk through closed system capability (3). This article will compare the workflows scaling out with roller bottles versus scaling up with cell factory systems, focusing on space requirements, investments, and environmental sustainability.
While both approaches are widely used, the differences between scaling out and scaling up become more pronounced as production volumes increase and facility constraints tighten.

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Differences in scale up and scale out

Transmembrane proteins are crucial for various cellular functions, including signaling, transporting, and maintaining structural integrity.

When expanding vaccine production, deciding between scaling out (using roller bottles) and scaling up (using cell factories) is essential to optimize resources and facility space. Scaling out roller bottles increases production by adding more bottles due to the limited surface area of each bottle. This approach requires extensive space and labor.

In contrast, cell factory systems are designed for scaling up, offering higher surface areas per vessel and increasing output within a single unit. This distinction can lead to more efficient resource utilization and potentially maximize production capacity.

Consideration	Scale-Out (Roller Bottles)	Scale-Up (Cell Factory Systems)
Expansion method	Add more individual vessels	Increase surface area per unit
Facility footprint	Large	Smaller
Labor intensity	High	Lower
Contamination risk	Higher (open handling)	Lower (closed system)
Sustainability	Higher resource use	Reduced footprint and waste

Here are three considerations when it comes to deciding between scaling up and scaling out:

1. Space requirements

The space requirement of each method is vastly different due to the number of vessels and equipment required. A facility dedicated to producing 850,000 cm² cell culture batch using the scale-out method with roller bottles requires approximately 2620 ft² of space to house 1,000 roller bottles, 24 racks, 4 seed incubators, and 8 biosafety cabinets whereas, to produce the same cell culture batch using the scaleup method with the cell factory systems, only approximately 970 ft² is required to house 34 units, 3 incubators, 1 manipulator, 2 seed incubators, and 1 biosafety cabinet. The scale-up method with cell factory systems saves approximately 1650 ft² of space compared to the scale-out method with roller bottles.

2. Investments

Regarding the investment to expand vaccine production through adherent cell culture, we examined the direct and indirect costs using roller bottles and cell factory systems. The direct costs that include labor, materials, and consumables are approximately 16% lower when using cell factory systems rather than using roller bottles. In terms of indirect costs from equipment capital and facility, they are approximately 11% lower when using cell factory systems over using roller bottles. These costs can increase further if bespoke robotics is integrated to manage the high volume of roller bottles.

3. Environmental sustainability

Sustainability is also a huge factor in modern vaccine production. Choosing between roller bottles and cell factory systems can impact the environment and resource use. Roller bottles need a bigger facility footprint and volume for the scale-out method, which contributes to a higher carbon footprint.

On the other hand, scaling up adherent cell culture using cell factory systems requires a smaller facility footprint and fewer consumables, which makes it more eco-friendly. Cell factory systems can be made with biobased feedstocks, further decreasing the carbon footprint from production, making them a more sustainable choice.

Because scale-up approaches rely on fewer vessels and reduced supporting infrastructure, cell factory systems typically lower energy demand and associated carbon emissions compared with large-scale roller bottle operations.

Summary

With growing demand for vaccines, identifying scalable and efficient methods for adherent cell culture is increasingly important. Roller bottles are a good option for lower-scale production environments. When the need to scale arises, they present many operational and process challenges such as labor, footprint, and issues associated with handling high volumes of open system vessels but can be challenging when scaling out due to contamination risks and inefficiencies.

Conversely, cell factories offer a lower footprint, standard automation allowing for reduced labor, and a closed system environment, reducing risk of contamination. Cell factory systems take up less space, use fewer consumables, and can lower labor costs. Adopting cell factory systems can provide a more viable solution for large-scale vaccine production.

Frequently asked questions

Scaling out increases production capacity by adding more individual culture vessels, such as roller bottles, each providing limited surface area for cell growth.

Scaling up increases output by using systems with higher surface area per unit, allowing more cells to be cultured within fewer vessels.

Scale-out approaches typically require larger facility footprints due to the number of vessels and supporting equipment, whereas scale-up approaches consolidate production into smaller spaces.

Scale-up approaches using cell factory systems are often better suited for large-scale vaccine production due to reduced labor, smaller footprint, and lower contamination risk.

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References

European Pharmaceutical Review (2025). MSD bolsters US manufacturing capacity with $1b investment.
Trump, Benjamin D. et al. (2022). Vaccine supply chain: Resilience-by-design and resilience-by-intervention. Vaccine 40 (2022) 1695–1698.
Whitford, William G., and Fairbank, Alain (2011). Considerations in Scale-Up of Viral Vaccine Production. BioProcess International, September 2011.