Applications of controlled freeze-thaw system in the production of modern biologicals

Vikrant is M.Tech in Bioprocess Technology with an accomplished 10+ years of experience in bioprocess Industry with a major focus on technology transfer, scale-up & validation of vaccines and biosimilars molecules. He has expertise in validation, downstream processing unit operation viz. chromatography, filtration-Depth, TFF & Nano-filtration. He has also been engaged in designing and successful qualification of BSL 2 manufacturing facility.

- Vikrant Hedau

With the advancement of science and technology and the development of the pharmaceutical industry, medical care and public health has become an important part for the safety of human life. With a rapid development of biomedicine in the entire pharmaceutical industry, biologicals have become an increasingly important treatment.

When biologicals are exposed to inappropriate conditions that are not effectively controlled during the production, their quality will be affected, which will endanger the lives of patients indirectly. For biologicals stored in a form of solution, the effective storage of raw materials and intermediates is very essential. For heat-sensitive biologicals, cryogenic preservation can ensure the activity of biologicals, and it is an effective and economical way in the current biopharmaceutical industry.

Generally, liquid biologicals are stored in an ultra-low temperature refrigerator or freezer at -40 to -80°C, and thawed through a water bath circulator at about 25°C or at room temperature (25°C). Traditional freezers and thaw biologicals containers are stainless steel or PE bottles or barrels.

However, these traditional freezing and thawing methods have the following problems:

1. The freezing and thawing rates are uncontrollable and cannot be repeated later;

2. The freeze-thaw distance (thickness) is different, and its process cannot be scaled up and controlled later.

3. The liquid loading and unloading is performed under an exposed condition;

4. There is lack of regulatory compliance (no electronic signatures, no electronic records, etc.).

With the above problems, it will cause the following disadvantages & risks:

1. The products or intermediates have low homogeneity, the biologicals have poor stability, and their quality has changed, with reduced activity and safety;