Scaling adherent cell culture from early-stage research to commercial manufacturing remains a significant challenge for biotechs, with complexities in process changes, validation, and automation. Joel Eichmann, co-founder and managing director of Green Elephant Biotech, explains how the company’s innovative CellScrew technology enables a seamless scale-up, reducing risk and cost while maintaining consistent cell culture conditions.

In this Q&A, he discusses key hurdles in scaling adherent cell processes and how Green Elephant’s approach supports biotechs at every development stage.

Why is scaling up adherent cell cultivation particularly challenging for biotechs?

Adherent cell processes begin in small-scale formats, such as T-flasks or well plates, which are easy to handle in early R&D. But scaling them up often means jumping to completely different systems, such as fixed-bed or hollow-fibre bioreactors, with entirely new handling, validation, and regulatory requirements. That transition requires a lot of time and resources. It increases time to market, process complexity, and costs.

What limitations do 2D cell culture processes present as operations grow?

ATraditional static 2D systems don’t offer economical scaling effects. As surface area needs grow, you add more vessels – but also more manual labour, cleanroom space, and repetitive process steps. With multi-layer systems in particular, handling becomes complex and labour-intensive, driving up costs quickly. That’s manageable in early development, but it becomes a major bottleneck in commercial-scale production.

Why is shifting to 3D cell culture often considered a disruptive or risky move?

Moving to 3D often requires adapting cell types and re-optimizing media and protocols. These changes that can significantly affect cell biology, yield, and product quality. Common issues are increased shear stress, unintended differentiation, and altered posttranslational modifications, all of which can compromise the therapeutic relevance of the product. For regulated processes, even small process changes may trigger extensive comparability studies or revalidation, making the transition costly and risky when initiated too late during product development.

How does Green Elephant Biotech’s technology support a smoother transition from small-scale to large-scale production?

Our CellScrew flask is a compact, dynamic 2D cell culture system that allows seamless scale-up. You can start with a scale-down model for early-stage development and scale up to clinical batches using the same system. For commercial manufacturing, we’re developing an automated, integrated cell culture platform that enables fully automated and monitored processes based on the CellScrew. This allows users to begin with the manual system without upfront CAPEX, and invest in automation later, as development progresses. The environment for the cells remains constant throughout, minimizing biological risk while enabling a low-friction scale-up.

Q: In what ways does your approach maximize surface area without requiring major process overhauls?
A: The CellScrew combines the best of traditional roller bottles and multilayer stacks. Its Archimedes’ screw enables gentle, low-shear mixing, while concentric cylinders provide a dramatically increased surface area within a compact footprint. This geometry allows dynamic culture of adherent cells retrofitting into standard roller devices and incubators.

Q: Can you share any examples or results from companies that have adopted your platform?
A: While we’re working closely with several companies in the cell and gene therapy field on process development projects, we’ve also supported biotechs in optimizing their cell banking workflows. In these cases, switching from labor-intensive protocols involving many T-flasks to a single CellScrew significantly reduced hands-on time and the risk of contamination in their cell banks.

What should biotechs consider early on to avoid scale-up bottlenecks later?

Biotechs need to think about manufacturing from day one. Even during preclinical development, choose platforms with a clear path to GMP. Avoid systems that are difficult to validate. Look for solutions that grow with your process, and that support automation and facility efficiency. Equally important: your QC strategy must scale with your process. Relying on microscopy may work in R&D, but it won’t hold up in a commercial environment. Scalable systems should offer online monitoring options and generate quantitative data for consistent decision-making. If you can’t measure it automatically, you probably can’t scale it reliably.

How do you see the future of adherent cell culture evolving, particularly in terms of scalability and automation?

Automation will be essential, especially for small-scale batches as we see them in cell and gene therapies. Automation does not only reduce labour cost, it ensures batch-to-batch consistency. Closed systems, single-use systems and integrated sensors are all part of that. At the same time, there’s growing pressure to reduce material waste and carbon footprint. So, we’ll see a shift toward sustainable, high-efficiency platforms that align with both regulatory and environmental expectations.

What’s next for Green Elephant Biotech and your mission to simplify scale-up?

We’re entering an exciting new phase. On the operational side, we’re expanding our production capacity and scaling up our GMP-compliant supply chain to meet growing demand from customers moving toward clinical manufacturing. At the same time, we’re investing heavily in the development of our upcoming automated cell culture platform. It is designed to reduce manual handling by over 90%, while enabling online monitoring and data-driven control of adherent cell culture processes. This allows customers to start small with a manual CellScrew setup and seamlessly transition to automated, scalable production as their needs grow – without changing the environment for the cells. Our broader mission stays the same: to make adherent cell culture truly scalable, practical, cost-efficient, and sustainable. We want to empower cell and gene therapy developers to focus on what matters most: delivering life-changing therapies and making them accessible for more patients.