Cooling systems are essential infrastructure for biopharma companies, keeping delicate biologics, cells and tissues preserved at deep cryogenic temperatures. When these systems fail, the consequences for both research and business can be disastrous.
In practice, critical deviations in cooling systems rarely stem from exceptional events. They arise during routine operations — transitions between process steps, opening of airlocks, or short-term load peaks. Initially subtle, these effects accumulate over time and ultimately impact the quality of pharmaceutical products.
“Many cooling systems are optimized for efficiency under ideal conditions, not for stability during real-world disruptions.” – Amine Ben Souissi
At the same time, most conventional cooling systems rely on an assumption that is rarely questioned: a stable power supply. But when this fails, control systems shut down and cooling capacity can collapse immediately. Cooling then becomes exactly what it is meant to prevent: a source of risk within the pharmaceutical process.
“Many cooling systems are optimized for efficiency under ideal conditions, not for stability during real-world disruptions,” says Dr Amine Ben Souissi, Market Manager Pharma North & Central Europe at Air Liquide.
Built In Autonomy
This distinction is leading to a shift in how cooling systems are evaluated. Efficiency remains important — but it does not prevent failure. What matters is whether a system continues to function under unstable conditions.
“The key difference with LN₂ is that cooling capacity is not tied to the power supply.” – Amine Ben Souissi
Liquid nitrogen (LN₂)-based cooling solutions are helping to redefine the approach. Unlike conventional cooling systems, with LN₂ the energy is stored directly within the medium, while electricity is only required for control and peripherals. As a result, these solutions maintain their cooling capacity even during power disruptions.
“The key difference with LN₂ is that cooling capacity is not tied to the power supply,” explains Ben Souissi. “That fundamentally changes how risk is assessed.”
With LN₂-based systems, autonomy isn’t an added benefit — it is built into the system itself.
An Integrated Approach
Another distinguishing factor for LN₂-based solutions lies in the system design. Instead of isolated cooling zones, temperature management is integrated across interconnected areas. Actively cooled zones transfer residual cooling capacity to adjacent sections, stabilizing them passively.
“Many challenges don’t arise within the core process, but at the points where materials, equipment, or conditions transition.” – Amine Ben Souissi
This approach reduces energy losses and addresses a frequently underestimated issue: process interfaces. “In practice, many challenges don’t arise within the core process, but at the points where materials, equipment, or conditions transition from one stage to the next,” says Ben Souissi. “That is exactly where stability must be ensured.”
“The cascade principle allows for precise control of different temperature ranges and optimizes LN₂ use,” explains Uwe Nehrmann of NNC-LIN MS GmbH. The approach links multiple temperature zones, allowing cooling energy to be transferred more efficiently across the system. The focus shifts from individual components to overall system performance.
Seeing is Believing
As pharmaceutical processes become more complex, the criteria are evolving for companies setting up or upgrading their cooling systems. Technical data can provide decision-makers with initial guidance, but — as Air Liquide has observed while working with pharmaceutical manufacturers across Europe — the deciding factor is ultimately the technology’s performance under real-world conditions.
“References are essential for investment decisions,” says Ben Souissi. “But only real-world operation shows how systems perform under varying conditions.”
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Site visits are no longer optional niceties — they are increasingly a key component of the decision-making process. For companies interested in exploring cooling systems, Air Liquide can arrange site visits at NNC-LIN MS GmbH as well as at reference installations where visitors can observe the systems in action.
“The ability to visit installations and speak directly with users changes the evaluation entirely. Many practical aspects only become clear in operation,” says Ben Souissi.
The Answer to a Key Question
Cooling remains essential in pharmaceutical production — but the criteria are shifting. While efficiency and temperature precision still matter, systems also need to be able to operate independently of external power and remain functional during disruptions.
Ultimately, the question is simple: does cooling still work when it matters most? For many, LN₂-based cooling solutions may be the answer they seek.