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

Experiment D, in which no bags were used, established that the heat transfer performance of all three cavities is reasonably comparable. The freezing of 3 x 90 L of water was completed in eight to nine hours (for this specific geometry, the simulated freeze time estimated using Fluent software is about nine hours), although the right-hand cavity was ~10% slower than the other two. For comparison, an IBI 300 L CryoVessel can completely freeze 300 L of water in 10–11 hours on the same freeze–thaw skid. Although in this experiment the bag holder is not operated in the intended configuration, this can be viewed as being the worst case scenario in terms of heat load on the freeze–thaw skid because there is no additional thermal resistance caused by the bag material or contact resistance. The results suggest that the heat transfer fluid flow is distributed fairly uniformly among the three cavities, although the right-hand cavity may be slightly more restricted.

A new set of bags was installed immediately preceding experiment A1. All of the remaining experiments, listed chronologically in Table 2, used the same set of bags. The heavy-duty adhesive tape used to anchor the top of each bag to the holder walls also provided some protection against moisture caused by condensation seeping between the bag and the holder walls. A thin water film present between the bag and cavity wall can significantly enhance the heat transfer rate by minimizing contact resistance. This can be seen by comparing the freeze time data for the center cavity in duplicate experiments A1 and A2. A closer inspection of the center cavity confirmed that large wall areas had been wetted. A comparison of the freeze time between the left and center cavities in experiment A1 also reveals that the performance varies from cavity to cavity, with the left cavity performing significantly worse than the center cavity (more than 16 hours versus 13.5 hours). In this instance, the discrepancy can be attributed to the poorer fit of the left side bag (no bag wall contact in some areas) compared to the center bag. The bags used in this study were manufactured by a manual process; hence, the dimensional tolerances are rather wide at 25 mm.

In experiment set B, the PC thermowells and dip tubes were added to each cavity. This addition did not have an effect on freezing performance. We also investigated the magnitude of heat transfer enhancement from having a wetted bag–cavity wall interface by intentionally introducing water in this area. In experiment B2, we injected water between the bag and the cavity wall of the center cavity. In this case, there was no noticeable decrease in freezing time as compared with B1, probably because that interface was already wetted from the condensation generated in previous freeze–thaw cycles. Injecting water in the interfacial region between the bag and wall of the left cavity, however, resulted in significant improvement in freezing time, as seen in experiment B3. The magnitude of this improvement is consistent with those seen for the center cavity in experiment set A. The thin layer of water reduced the contact resistance between the bag and cavity wall.

Figure 6.
The temperature traces for experiment set B are shown in Figure 6 and give a measure of reproducibility from experiment to experiment. Note that the freeze or thaw time for the right -hand cavity does not vary appreciably, indicating that there was minimal moisture ingress between the bag and cavity wall throughout the studies. Hence, the right cavity serves as an internal control for the various experiments.

In experiment sets B and C, the cavity monitored by the temperature probe also underwent recirculation mixing during the last three hours of thaw. Interestingly, the thaw times show little variation across all experiment sets, ranging from approximately nine to 10.5 hours, irrespective of cavity location, contact resistance, or recirculation. In IBI 300 L vessels, 300 L of water can be thawed in approximately eight to nine hours using the same freeze–thaw skid. Unlike the freezing process, controlled by conductive heat transfer where the thermal resistance increases as ice is formed, the thaw process is primarily dominated by natural convective heat transfer. As thaw proceeds, the heat transfer rate between the container walls and the contents does not change drastically.

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