Applying Continuous-Flow Pasteurization and Sterilization Processes - The author discusses HTST pasteurization and UHT sterilization. - BioPharm International


Applying Continuous-Flow Pasteurization and Sterilization Processes
The author discusses HTST pasteurization and UHT sterilization.

BioPharm International
Volume 26, Issue 8, pp. 38-41

Sterliization Continuous Manufacturing
Continuous manufacturing has been described as a manufacturing breakthrough and as the method of the future by Konstatine Konstantinov, vice-president of commercial process development at Genzyme (now part of Sanofi), and Robert Bradway, chairman and CEO of Amgen (1, 2). The trend toward using this method is increasing as manufacturers of bio/pharmaceuticals strive to meet growing demand, reduce floor space, improve manufacturing flexibility and capacity, and reduce costs.

The adoption of continuous manufacturing for biopharmaceuticals emphasizes the need to inactivate microorganisms continuously at rates consistent with these new processes. The adoption of HTST and UHT continuous processing and surrounding technologies is a natural fit. Early adopters in the biotechnology and biopharmaceutical industries have begun to deploy these processes. The question remains, however, what are the reasons to adopt HTST and UHT in these industries? Are their benefits simply a function of the continuous process or are there additional benefits that make HTST and UHT even more desirable?

Figure 1: Flow diagram for continuous-flow thermal processes. (ALL FIGURES COURTESY OF AUTHOR)
Benefits ofF HTST and UHT
The benefits of HTST and UHT processes result from their continuous flow nature and their use of different and more highly refined time and temperature conditions. To understand their benefits, it is useful to consider an example process like that shown in Figure 1. The product is pumped continuously through the process at constant flow and is heated to the process temperature under steady-state conditions. It flows through the hold tube, which is of sufficient length to ensure that the product is hot for the time needed for the required lethality, before it is cooled as it exits the system. The result is that the product experiences a controlled, well-defined time–temperature exposure. This time–temperature history (TTH), conceptually shown in Figure 2, is usually less than two minutes from start to finish. Although there are relatively few rules linking the terms "pasteurization" or "sterilization" to specific temperatures, for the sake of this discussion, pasteurization is usually conducted at hold-tube temperatures between 70 C and 121 C. Sterilization hold temperatures range from 128 C to 150 C. Hold times most commonly range from 2 to 30 seconds.

Figure 2: Conceptual plot of product time–temperature history.
Because HTST and UHT continuous-flow processes are closed systems that operate at steady state, the impact of the thermal process on product quality and lethality is uniform and independent of batch and container size. In contrast, the thermal exposures delivered to liquids being pasteurized or sterilized in large-scale fermenters or vessels in autoclaves/retort are not as uniform because the heat exposure varies with the container size and location. In comparison, it becomes apparent that, in the continuous process, several major sources of variation and potential points of failure have been eliminated and overprocessing has been greatly reduced.

As thermal processes, HTST and UHT processes are effective against viral contamination. These processes are especially useful for emulsions and suspensions that are not compatible with filtration. They provide real-time monitoring and record-keeping of processing conditions. They are precise, and the actual process time and temperature conditions can be adjusted to optimize the retention of key components and the delivered lethality. This precision can be important to maximize retention of key media components being fed into a fermentation process or of a desired active agent resulting from a different step of manufacture.

Unlike scale-up of batch operations, scale-up of HTST and UHT processes is often unnecessary because processing more material is linked only to the processing time, not the vessel size. Larger volumes of product are processed by simply running the equipment longer. Thus, multiple systems may not be needed for different batch sizes. When scale-up is necessary within the same general style of HTST or UHT equipment, it is a matter of duplicating the TTH. If a different style system is used, the detailed matching of the TTH may require more powerful mathematical and modeling tools for thermal process evaluation.

In the food industry, these processes are used to make many high quality products that would not be viable using longer-time and lower-temperature methods, such as autoclaving, because of poor quality. These examples demonstrate the potential to pasteurize or sterilize many bio/pharmaceutical materials that are also not well-suited to autoclaving. In simpler terms, these are enabling technologies.

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