New solutions for the pharmaceutical industry

With its extensive experience in gases and cryotechnology, Linde supports the pharmaceutical industry with innovative processes, high-performance products, and practical services. This year at Interpack, the company is showcasing new solutions for the reproducible freezing and thawing of pharmaceutical products in larger containers – known as bulk freezing. Additionally, visitors can learn about the highly efficient ice fog process VERISEQ® Nucleation for controlled ice crystal formation at the trade fair stand. This solution was developed in collaboration with IMA Life, specifically for the freeze-drying of sensitive pharmaceutical products and biological compounds. VERISEQ® Nucleation accelerates the complex production process and ensures homogeneous ice crystal formation (nucleation), which improves the quality of the final product.

In this commercially usable process, ice fog is generated outside the freeze-drying chamber in a mixing device by combining cold nitrogen with hot water vapor. When these ice crystals are subsequently introduced into pre-cooled glass vials containing the pharmaceutical product to be freeze-dried, they serve as nucleation points from which ice crystal formation begins. This allows for a rapid and uniform ice crystal formation at a specifically chosen sub-cooling temperature, both within individual vials and across the entire batch.

The addition of the ice fog occurs in two steps: first, the vials with the products are cooled to or below a specific temperature, typically at or below their freezing point. Then, the ice fog is introduced to trigger ice crystal formation.

To enable industrial-scale application of this process, a special mixing device has been developed. It allows for efficient and rapid generation of ice fog and circulation within the entire freezing chamber. Almost all freeze-dryers, whether sterilizable or non-sterilizable, can be retrofitted with this technology. Furthermore, the process requires no extensive modifications to the production process: once the desired product temperature is reached, only a signal exchange is needed to start and stop the ice fog process. The internal sequence is fully controlled by the nucleation unit's control logic. VERISEQ® Nucleation can thus be used both in laboratory conditions and on an industrial scale.