Design and Testing of a Prototype Large-Scale Bag Freeze–Thaw System - The development of a large-scale bag freeze–thaw system will have many benefits for the biopharmaceutical industry. -

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Design and Testing of a Prototype Large-Scale Bag Freeze–Thaw System
The development of a large-scale bag freeze–thaw system will have many benefits for the biopharmaceutical industry.


BioPharm International Supplements


Prototype Bag Holder Design


Figure 3.
To satisfy the design requirements, we selected a rectangular shape (Figure 1d) with dimensions that would accommodate a 100-L fill volume (the actual volume is larger to account for expansion of the ice). In the proposed system, three bags can fit into a three-cavity jacketed holder that provides the same capacity and occupies the same footprint as the IBI 300 L CryoVessel. Figure 3 shows the dimensions that were specified for the manufacture of the first prototype holder and bags. The bottom angle of five degrees allows for drainage of the bag contents. Each vertical wall was purposely designed with a one-degree outward tilt from bottom to top to ensure that the bag contents freeze from the bottom up. The dimensions were chosen with consideration to manufacturability and performance. Compromises had to be made to satisfy all constraints. For example, narrower cavities would yield faster completion of freezing but would be more difficult to fabricate.

At-scale Protptype Testing

Physical Description


Figure 4.
The prototype bag holder (Figure 4) was fabricated in accordance with the dimensions presented in Figure 3. Each cavity is independently jacketed and connected in parallel to a common cooling loop inlet and outlet. A drain opening is present at the lowest point in each compartment to permit fluid removal during cleaning. The final production unit should have a cover for each cavity that would provide additional moisture blockage as well as anchor points for the hoses and accessories from each bag. Additionally, a single large insulated lid would cover the top of the bag holder for thermal protection.

Matching bags with a nominal capacity of 117 L each were manufactured by Thermo Fisher Scientific (Logan, UT), in the 3-D configuration from HyQ CX3-9 film.

Experimental Setup

Preliminary performance testing was conducted using an IBI CU5000 freeze–thaw skid. The freezing set point was –50 C, and the thawing set point was 25 C for 12 hours, then stepped down and held at 5 C until stopped.

The bags were inserted into the cavities and gently inflated with compressed air to expand all the folds in the plastic film before filling the bag with liquid. The first set of experiments was conducted with deionized water at the 100-L fill level. It was discovered that the jacket surrounding each cavity did not extend sufficiently close to the top, resulting in long freeze and thaw times for the top 2–3 cm layer of liquid. This problem can be resolved in a subsequent prototype holder by designing deeper cavities to account for the gap in the jacketing. For the current prototype, all subsequent experiments were conducted with a 90-L fill volume.

The prototype bag provided a port fitted with a flexible weighted internal hose intended as the dip tube for fluid introduction and removal. A similar arrangement without the weight was to serve as the thermowell (in this case, the hose end was welded shut) that can accept a probe for temperature monitoring during the freezing and thawing operation.


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