The conditions under which pharmaceutical products are freeze dried are subject to strict standards. Satisfying these requirements is crucial for pharmaceutical companies for proving that their products have been safely manufactured and are suitable to be used in patients.
In most cases, each freeze dryer manufacturer has its own integrated control system to monitor the freeze drying process, as key parameters that include humidity, temperature and pressure (or vacuum).
The system that records the data also independently activates active warnings and alarms if the accepted process parameters are exceeded. These often incorporate a time delay and/or a hysteresis. This activates the alarm once the parameter has exceeded acceptable levels for a certain amount of time, which helps prevent annoying alarms.
It is important to perform a regular calibration check and to be able to perform full calibration adjustment for the system inputs as it is important to verify that the measurements made are reliable.
All data from the freeze drying process should be recorded. Where data recorders are used, the requirements of the International Society of Pharmaceutical Engineers (ISPE)’s Good Automated Manufacturing Practice (GAMP) will also apply, including the stipulation that any recording equipment has to be validated for use in pharmaceutical processes. A recorder with Ethernet connectivity allows historical recorded data and alarm and audit trail information to be retrieved automatically to a central database where archive and analysis, if required, can take place. Any electronic recording equipment also has to be compliant with the 21 CFR Part 11 rule, which aims to give electronic records and signatures the same weight and trustworthiness as their paper-based counterparts. A key aspect of 21 CFR Part 11 is its focus on security, particularly relating to the prevention of data tampering and the ability to identify specific individuals and events involved in the production and / or data management processes.
Any control system used for a freeze drying application should ideally be capable of automatically adjusting the process to maintain the ideal conditions. Traditionally, open loop control systems have been used, with the freezing and heating temperatures and the chamber pressure being controlled according to a specific profile. However, this approach has several drawbacks, including the inability to cope with temperature variations outside of the set profile. With no way of accelerating the process if conditions change, the overall freeze drying period is also prolonged.
For optimum control of the freeze drying process, a closed loop control system should instead be used. Data from the pressure and temperature sensors is fed back to the controller where it is compared against a reference value. The controller takes the difference between the output and the reference value and uses it to change the inputs to the system to help compensate for the difference. The result is a more dynamic and precise control of the freeze drying process, with the ability to address any unexpected fluctuations in process conditions.