Freeze-drying technology has been constantly evolving. In terms of validation, quality-by-design (QbD) has replaced the classical approach to increasing product knowledge.
With QbD, a design space can be defined in which the process can vary without impacting the
critical quality attributes of the product.
The next advancement will be to develop a
dynamic system, one able to give information on sublimation and product temperature evolution during the cycle, to replace
the static system. In terms of validation, a
commonly used strategy is one in which
the heat transfer coefficient for the device
and the freeze-dryer is determined. The
resistance of the product is measured, and
freeze-dryer capability monitored to avoid
With those three elements,
the scale-up and transfer of product is no
longer empirical but can be predicted. The
sensors able to monitor the cycle are also
evolving. For example, a mass spectrometer can be installed on a freeze-dryer that
uses wireless probes to determine potential
leakage of silicone oil. This tool can also
monitor the end point of primary drying.
In the past, refrigerants were improved to
avoid ozone depletion, but they still have
a high potential to contribute to global
warming. The 2015 F-gas regulation targets cutting these emissions in the United
States by two-thirds by 2030, and the first
major reduction has recently come into
force. In 2018, the distributor may sell
only refrigerants with a CO2 equivalent
to 63% of the 2015 level. Consequently,
the race is on to find new refrigerants for
freeze-dryers before the supply runs out.
Fortunately, an alternative is arising in
These topics and others will be discussed
during the next PDA Europe Pharmaceutical Freeze Drying Technology conference
at the end of November.
Learn more about the Pharmaceutical Freeze Drying Technology conference.
Disclosures: Thomas Beutler is Head of Liquid Dosage Application Development at GEA Lyophil GmbH, Hürth, Germany. Yves Mayeresse is Director of Manufacturing Science and Technology, Primary Process, Lean Process and Visual Center of Competency at GSK, Wavre, Belgium.