Page/Steiner: The most important aspects of understanding the process are those that give an insight into the experience of the individual vial rather than simply measuring the integrated effect on the headspace. Simple aggregated measurements, such as chamber pressure or more complex measurements like the application of mass spectrometers to the chamber gas, all have value for overall process control.

To understand the range of process conditions caused by both forced and natural variation within the overall system of the equipment, the vials and the product, it is important to be able to characterise the range of experiences of individual vials. However, the problem is that techniques examining the individual vial that can be used during development and validation are frequently difficult to deploy in a large production dryer.

Pikal: The key properties to measure are product temperature and primary drying time. Unfortunately, product temperature in given vials cannot be measured in a representative way. Insertion of temperature probes reduces the degree of supercooling, making the measured temperatures nonrepresentative of the batch as a whole. This problem can be circumvented, however, by using controlled ice nucleation, but although this technique is now available in both laboratory and production equipment, it is not routinely used in manufacturing. Hopefully, this will change in the near future. There are also indirect ways to measure batch average temperature, such as MTM or TDLAS that could be used in manufacturing (particularly TDLAS), but so far, this is not common practice.

Yves Mayeresse is Director, Manufacturing Center of excellence filling and freeze-drying operations, at GSK Biologicals.

Steven Nail is a Principal Scientist at Baxter Pharmaceutical Solutions.

Trevor Page is Group Technical Director at GEA Pharma Systems.

Michael J. Pikal is Professor of Pharmaceutics at the School of Pharmacy, University of Connecticut.

Manfred Steiner is Area Sales Manager at GEA Lyophil GmbH.