With 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 pharmaceutical industry, biologicals have become an increasingly important treatment.

When biologicals are exposed to inappropriate conditions that are not effectively controlled during the production, the 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(such as mAb, vaccine,blood plasma,insulin,probotics,growth hormone,etc.),cryogenic preservation can ensure the biological activity, 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.

The Problems of  Traditional Freezing & Thawing Methods

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

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

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

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

The Disadvantages & Risks of Traditional Freezing & Thawing Methods

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

Ÿ   There is risk of microbial contamination;

Ÿ   The biologicals have shortened shelf life;

Ÿ   The production cost increases and the production efficiency decreases.

However, the traditional freezing and thawing method is still used by most biopharmaceutical companies, mainly because of the cost.

The Development of Controlled Freeze &Thaw Systems

When the biologicals are transformed from the R&D stage to the commercial large-scale production stage, biopharmaceutical companies have to consider the following: how to guarantee the consistency of process scale-up and how to increase the production capacity during commercial production.

 First of all, biopharmaceutical companies need to consider the matching of the capacity of the freezing steps with the upstream and downstream. Secondly, biopharmaceutical companies need to minimize production costs and improve efficiency while guaranteeing the product quality and safety. Although traditional methods are still widely used in the R&D of modern biopharmaceutical industry and can achieve some effects, the traditional freeze & thaw methods need to increase the labor works, enhance the risk of product contamination and add a complex validation process after the products have entered the clinical and commercialization stages.

The controlled freeze& thaw systems integrates freezing and thawing

processes. This system is different from the traditional ultra-low temperature refrigerator and water bath circulator. By using the controlled

With 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 pharmaceutical industry, biologicals have become an increasingly important treatment.

When biologicals are exposed to inappropriate conditions that are not effectively controlled during the production, the 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(such as mAb, vaccine,blood plasma,insulin,probotics,growth hormone,etc.),cryogenic preservation can ensure the biological activity, 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.

The Problems of  Traditional Freezing & Thawing Methods

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

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

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

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

The Disadvantages & Risks of Traditional Freezing & Thawing Methods

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

Ÿ   There is risk of microbial contamination;

Ÿ   The biologicals have shortened shelf life;

Ÿ   The production cost increases and the production efficiency decreases.

However, the traditional freezing and thawing method is still used by most biopharmaceutical companies, mainly because of the cost.

The Development of Controlled Freeze &Thaw Systems

When the biologicals are transformed from the R&D stage to the commercial large-scale production stage, biopharmaceutical companies have to consider the following: how to guarantee the consistency of process scale-up and how to increase the production capacity during commercial production.

 First of all, biopharmaceutical companies need to consider the matching of the capacity of the freezing steps with the upstream and downstream. Secondly, biopharmaceutical companies need to minimize production costs and improve efficiency while guaranteeing the product quality and safety. Although traditional methods are still widely used in the R&D of modern biopharmaceutical industry and can achieve some effects, the traditional freeze & thaw methods need to increase the labor works, enhance the risk of product contamination and add a complex validation process after the products have entered the clinical and commercialization stages.

The controlled freeze& thaw systems integrates freezing and thawing processes. This system is different from the traditional ultra-low temperature refrigerator and water bath circulator. By using the controlled freeze &thaw method, the system can provide liquid biologicals, especially biological macromolecule intermediate with controlled (timely feedback  and revise for the application of process analysis techniques), repeatable (freezing and thawing of products with the same specifications, process scale- up from R&D to the commercial production), and powerful (efficient cold and heat exchange technology) freeze&thaw environments. The controlled freeze & thaw system can not only reduce the risk of microbial contamination, but also effectively extend the shelf life of the product while guaranteeing the product quality and stability.

Tofflon Controlled Freeze & Thaw Systems

Tofflon has independently developed the controlled freeze & thaw systems (horizontal type and vertical type as shown in Figure) based on its experiences in the shelf high-efficiency heat exchange (refrigeration, heating) and the application needs on the biological markets. Its freezing effect and its features as below: