Blast Freezer in Biopharma: What, when and why?
Blast freezers have emerged as a reliable solution in the biopharmaceutical industry. However, pharmaceutical bulk freezing is not just about turning liquids into solids; it is also about preserving the integrity and quality of life-saving drug substances during manufacturing processes. Not all biopharmaceutical products can be frozen the same way, however. There are different types of bulk pharmaceutical freezers on the market for good reasons. When and why are blast freezers used?
This article provides an overview of the types of bulk pharmaceutical freezers used in biopharma, the principles of blast freezing, and its suitability for different drug substances and container formats.
5 critical considerations when freezing bottles
The blast freezing technology
What is a blast freezer? Blast freezing relies on forced air convection inside a freezing chamber to rapidly reduce the temperature of drug substances. Cold air is circulated at high speed around the containers, ensuring uniform heat transfer and minimizing the risk of thermal gradients.
Unlike static freezers, blast freezers are engineered for pharmaceutical applications to freeze drug substances by maintaining consistent airflow. Controlled rate freezing is essential for preserving the integrity and quality of sensitive biologics. This process helps prevent cryoconcentration and ice crystal formation, which can compromise product quality.
What drug substances are frozen with air blast freezers?
When to use blast freezers? They are particularly effective for freezing high-value drug substances that are stored in rigid containers. Common examples include:
- Live attenuated vaccines: These biologics require rapid and uniform freezing to maintain potency and prevent degradation.
- Bulk biologics: Enzymes, recombinant proteins, and other biologically active substances benefit from controlled freezing to preserve activity and stability. [[1]]
- Monoclonal antibodies (mAbs): When filled into bottles, mAbs are often frozen using blast freezers to ensure consistent product quality across batches.
However, the suitability of blast freezing depends not only on the drug substance but more on the container format and the required freezing profile.
What single-use containers work best with pharmaceutical blast freezers
Why use blast freezers? Container compatibility plays a crucial role in the effectiveness of the freezing process. Plate freezing is the preferred way to freeze biopharmaceutical products in single-use bags, which is mainly due to their flexible structure. However, bags may experience uneven freezing in blast freezers, which can affect product quality.
Therefore the following bulky container formats are preferred for blast freezers:
- Bottles: Rigid and uniform in shape, bottles allow for optimal airflow and consistent freezing.
- Bulky containers: Larger containers, such as 3D single-use bags, drums and CryoVault®, can be accommodated with customized airflow systems to ensure uniform temperature distribution.
Key challenges in drug substance freezing
Freezing drug substances is a crucial step in biopharmaceutical manufacturing, but it comes with several hurdles. One of the main issues is matching the freezing method to the container type – what works for single-use bags may not suit bottles or stainless-steel vessels. Inconsistent freezing profiles across batches can also affect product quality, making precise process control essential.
As production scales up, freezing systems must keep pace while meeting GMP-relevant quality standards. And throughout the process, protecting the integrity of the biologic is critical. Ice crystal formation and thermal stress can compromise stability, so careful control of freezing conditions is a must to maintain product integrity.
What we learnt from tests about cryoconcentration in bottle freezing
Choosing the right freezing technology for bottles
Selecting the appropriate freezing method for drug substances in biopharma is not a one-size-fits-all decision. It depends on several factors, including the type of drug substance, container format, required freezing rate, and process scalability.
Blast freezing, with its air convection technology, is well-suited for rigid containers such as sterile bottles. It offers uniform temperature distribution and controlled freezing profiles, which are essential for maintaining the stability of sensitive biologics.
In contrast, plate freezing is preferred for flexible containers like single-use bags, where direct contact with cold surfaces ensures rapid and even freezing.
Static freezing, often used in legacy systems, lacks the precision and consistency required for modern biopharmaceutical processes to cool liquids and is more appropriate for storage of already frozen drug substances. It cannot control temperature gradients and results in longer freezing times, increasing the risk of cryoconcentration and product degradation.[[2]]
Freezing solutions from Single Use Support
Single Use Support offers a comprehensive portfolio of freezing technologies tailored to the needs of biopharma, including plate-based freezers, cryogenic liquid-nitrogen freezers and blast freezers. The latter is best for controlled freezing of bulk-packaged drug substances, such as biopharma bottles.
These integrated systems that support scalable workflows and are ready for GMP use. They are designed to ensure consistent product quality, operational efficiency, and flexibility across various container formats and drug substance types.
Controlled blast freezing with RoSS.BLST
References
- Singh S. et al.: Large-Scale Freezing of Biologics, 2009. Available at: Large-Scale Freezing of Biologics
- Brandmayr P.: Optimization of the freezing process with a liquid nitrogen freezer to increase cell viability of a mammalian cell line. 2023
