As batch sizes for bulk drug substances continue to grow, many biopharmaceutical facilities are reaching the limits of their existing freezing and storage infrastructure. At first glance, this appears to be a capacity issue, but in reality, it often highlights opportunities to optimize manufacturing facility design. Freezing and ultra-cold storage are frequently treated as separate unit operations. As a result, they are planned, implemented, and optimized in isolation.
At the same time, CDMOs and multi-product facilities are under increasing pressure to handle multiple primary packaging formats, ranging from single-use bags to bottles, within the same infrastructure. This adds another layer of complexity to freezing and storage operations.
In practice, this separation leads to additional material handling, fragmented workflows, and avoidable operational complexity. By contrast, a more integrated approach, where freezing and storage are aligned as one continuous batch process and designed for format flexibility, can simplify operations and improve overall efficiency without increasing facility footprint.
To explore this topic further, we asked Claus Exenberger, Freeze & Thaw Expert at Single Use Support, about his perspective.
What are the key challenges in bulk drug substance cold chain handling today?
Claus Exenberger: One of the biggest challenges is that batch volumes are increasing, while existing infrastructure remains unchanged. Expanding cold rooms or adding more freezers isn’t always feasible.
"At the same time, facilities – especially those of CDMOs – need to handle different primary packaging formats depending on the product or customer. Freezing and storage systems are not always designed to accommodate this degree of operational flexibility." Claus Exenberger, Single Use Support
When freezing and storage are not aligned as a single, integrated process, this leads to extra transfers, increased internal movement, and more manual handling than necessary. All of this adds to operational complexity and makes scalability more difficult.
Why is it a problem when freezing and storage are not aligned as one batch process?
Claus Exenberger: When freezing and storage are planned independently, you often end up splitting batches across multiple storage units. That means more handling steps, more coordination, and a higher potential for deviations.
If you add multiple container formats into the mix, things become even more complex. Some systems are only partially format-flexible, so operators have to adapt workflows depending on the packaging instead of following a consistent, standardized process.
It’s not just about equipment; it’s about workflow design. A lack of coordination introduces inefficiencies across the entire cold chain, and those inefficiencies usually become apparent in day-to-day operations.
How do RoSS.BLST and RoSS.ULTF address these challenges?
Claus Exenberger: RoSS.BLST and RoSS.ULTF are designed for different steps, but they deliver the greatest value when implemented as a combined system.
RoSS.BLST supports controlled blast freezing across different container types, while RoSS.ULTF is optimized for high-density, ultra-cold storage of those same formats. That level of compatibility is important, especially compared to more limited or semi-flexible solutions. Modular interior options for a wide range of bioprocessing containers further enhance the aspects of maximizing chamber utilization and processing efficiency.
Because both systems are aligned in terms of batch volume and material handling, they enable full-batch processing without disrupting the process flow, regardless of the primary packaging.
"This harmonization results in improved process control, reduced manual intervention, and the ability to increase capacity within the same facility footprint.” Claus Exenberger, Single Use Support
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What does this look like in daily operations?
Claus Exenberger: In daily operations, process become significantly more streamlined and predictable. Instead of adjusting workflows for different containers or breaking batches apart, operators can work with a consistent, batch-oriented approach.
The batch-wise move-in, move-out setup allows material to be frozen in RoSS.BLST and transferred directly into RoSS.ULTF using the same handling concept, regardless of whether bags or bottles are used.
There’s no repacking, no redistribution, and no unnecessary back-and-forth. That reduces operator workload, simplifies logistics, and lowers overall handling risk. For CDMOs in particular, this kind of format and process flexibility is essential to handle different products without increasing operational complexity.
Freezing and Storage of Bulk Drug Substance Batches
With rising biologics volumes, and while facilities remain unchanged, freezing and storage are increasingly treated as separate unit operations. This leads to fragmented workflows with additional handling steps, increased internal transport, and elevated risk.
This app note explores how to build freezing, transfer and ultra-cold storage steps as one continuous operation, ensuring a safe, scalable cold chain process for bulk drug substance batches.
Claus Exenberger is Technical Product Owner at Single Use Support. As product owner of freeze and thaw plaforms and the RoSS shell, the secondary packaging of single-use bags, Claus and his team develops further products that advance handling and freezing of single-use bags and bottles for the biopharmaceutical industry. With his working experience of 7+ years at Single Use Support he is expert in the protection of all available single-use bioprocess containers. His proximity to customers helps connect his process-oriented approach with the technical development of products.
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