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. -


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

A large-volume freestanding or minimally enclosed bag would be difficult to handle and offer insufficient protection against puncture. A solution to this problem is to use the bag as a liner inside a non-disposable container. This "bag in a can" approach offers puncture protection as well as blockage against vapor transmission though the bag wall. The basic incarnation of this type of container would be a simple, thin-walled metal shell which would be placed in a freezer and rely solely on convected cold air for freezing the contents. Based on computer simulations, however, the freezing time for such a device would be unacceptably long. A better solution would be to fully jacket and insulate the container, similar to a traditional freeze tank, and use the current freeze–thaw skids to provide the require cooling.

Table 1. Characteristics of bag shapes depicted in Figure 1.
The cost of the jacketed bag holder would be significantly higher than a simple enclosure. This configuration is necessary to achieve a sufficient heat transfer rate to freeze the bag contents in an acceptable amount of time. An additional benefit of this design is that the jacketing assembly provides thermal insulation protection during transport. Furthermore, because the product does not contact the metal surface, the container or shell can be fabricated from a low grade, less costly, metal alloy.

Figure 1.
Various container shapes and dimensions were considered during the initial design phase of the project. Figure 1 depicts several such containers. The rationale behind our selection or dismissal of each candidate is summarized in Table 1. We conducted transient simulations of the freezing process for water in the basic shapes shown in Figure 1 using fluent computational fluid dynamic software with the solidification model. Figure 2 shows the results of the simulations in the form of remaining liquid fraction as a function of freezing time for each of the basic shapes. Also plotted for performance comparison purpose is the Fluent simulation result for the commercially available Integrated Biosystem Inc., (IBI) 300 L CryoVessel. In that case, the freezing time obtained experimentally was within 15% of the simulation value. These simulations represent the best possible cases because we did not account for resistance caused by the bag material or the contact resistance stemming from microscopically imperfect contact between the walls of the container and the bag.

Figure 2.
The results from the simulations show that for these basic shapes, the overall freezing performance follows the cooled surface area to volume ratio, as expected. The IBI 300 L vessel has a wetted surface area to volume ratio of 0.157 cm-1 but this value includes contributions from the internal fins, which are not active cooling surfaces. Although composite shapes, as shown in Figure 1e, provide more cooling surfaces, the increased complexity in manufacturing both the holder and the bags negate the benefits of these configurations.

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