FRESH PERSPECTIVES
differential measurement between the pirani and capacitance manometer vacuum sensors. This makes sense, since the sublimation process is no longer absorbing the energy generated by the shelf.
AccuFlux enables the Kv to be measured for a specific vial type, fill, and vacuum level. With the known vial conductivity (Kv), AccuFlux provides the heat flow information allowing the product temperature to be determined during the primary drying cycle, without the use of a thermocouple. The product temperature allows the shelf temperature to be controlled to maintain the product close to, but not exceeding its critical temperature. For example, in Figure 10, the shelf temperature was maximized while keeping the product temperature at Tproduct critical – 20C. In this case, the Tproduct critical temperature used was -320C, so the product was held at or below -340C. The result was a further reduction in primary time, down to 19.3 hours. (Figure 10)
Since the process was monitored and controlled during both the freezing process and drying process, the entire process can be verified and repeated to ensure that a quality product is produced in each and every run.
FreezeBooster and AccuFlux in combination provide a true real-time Process Analytical Technology without the use of thermocouples and other invasive techniques. For the first time, the entire freezing and primary drying processes can be monitored and controlled. The technology combination is referred to as LyoPAT™. Implementing LyoPAT enables control of both the freezing and drying processes which results in a significant reduction in processing time, a more uniform end product, and a method to qualify that the product has been freeze-dried properly.
Another possible application for this methodology is the ability to monitor and control heat flow to enable a laboratory-sized system to simulate the heat flow pattern of a production freeze dryer or any other freeze dryer. Therefore, protocols could be developed and transferred to production from the lab consistently and confidently.
Please note: Features and processes described in this article are patent-pending.
Acknowledgements
The author wishes to thank and acknowledge Robin Bogner at the University of Connecticut for her technical assistance and consultation, Matthew Ling of Millrock Technology for his insights and support, and Ed La Borde of Millrock Technology for his diligent work in the lab.
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Editorial, “Controlling Ice Nucleation During the Freezing Step of Lyophilization”, Pharmaceutical Technology May 2013
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Awotwe-Otoo, D., Agarabi, C., Read, E.K., Lute, S., Brorson, K.A., Khan, M.A., Shah, R.B., Impact of controlled ice nucleation on process performance and quality attributes of a lyophilized monoclonal antibody, International Journal of Pharmaceutics (2013)
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74 American Pharmaceutical Review | Fresh Perspectives 2013
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