* * * INSIGHT * * *

   Role of Product Temperature in the Lyophilization Process

by 

Thomas A. Jennings, Ph.D.

ABSTRACT: This INSIGHT shows that there is an interrelationship between the product temperature, shelf temperature, chamber pressure and time. During the freezing process, the formation of a completely frozen matrix will be related to the shelf temperature and time. This interdependency of the temperature and pressure process parameters is most pronounced during the primary  drying process where the degrees of freedom of the product temperature, with respect to the shelf temperature and the chamber pressure, approaches 0. In order to ensure completion of the primary drying throughout the batch, the completion of the primary drying should be based on the frequency distribution of the C_o values for the containers. For the secondary drying, the residual moisture in the product will be dependent on the partial pressure of water vapor in equilibrium with product surface and the temperature of the product.

In the absence of monitoring the product temperature, there is a degree of uncertainty regarding the verification that the criteria for the lyophilization is achieved through the entire process. This degree of uncertainty is enhanced by (a), the design of the various segments of the lyophilization process; (b), the type and accuracy of the pressure and temperature sensors and (c), the design, construction and possible malfunctions in the operation of the freeze-dryer. Without product temperature monitoring, absolute verification that the lyophilization process was conducted within a given set of operating parameters becomes a matter of conjecture.

Various forms of product defects are considered and how they relate to deviations in either the chamber pressure, the shelf temperature or a combination of these parameters. The identification and location of the source contributing to these defects was shown to be hampered by the lack of product temperature monitoring. Product temperature monitoring is an essential key aspect for establishing a high degree of confidence throughout the lyophilization process.

Volume 1 No. 2                                                                                                April 1998

12 Pages           32 References          No Figures

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