Digital_Lyo

The number of biopharmaceutical injectable products continues to increase. Predictions are that 40 per cent of new molecular entities will require batch freeze-drying for stability. The freeze-drying process (lyophilization) removes water from sensitive or high-value products such as vaccines, biologics, antibiotics, to extend shelf-life without the need for refrigeration/cold-chain. Freeze-drying processes need to be sustainable and commercially viable. There is a need to accelerate batch throughput and build capacity to increase efficiency and enable timely response to unexpected demand (e.g. COVID-19). Shortening drying times reduces energy demands and emissions and improves efficiency so lowering end-product costs. This aligns with the Clean Growth Strategy.

A pharmaceutical product development programme involves optimisation of formulations and processes for product viability and consistency; but product quality issues are identified at the end of a long cycle and at this stage significant costs have already been incurred. In-situ rapid analytical monitoring, giving real-time automated data, will provide feedback on and enable control of the lengthy freeze-drying process. Such insight can enable shortening of development times, reduced repeat runs and product failure/loss, lessened environmental costs and bioburden and ultimately improved product quality and consistency.

Freeze-drying employs high-global warming potential (GWP) refrigerants (banned 2030) or liquid nitrogen (high energy use in manufacture) for cooling, and improving sustainability requires a fresh approach. Implementation of a continuous freeze-drying Peltier system would be capable of a step change reduction in emissions. Further, freeze-drying processes must be repurposed for the expected increase in personalised medicines and the smaller batch runs and 'just-in-time' production schedules that this involves.

By building a consortium encompassing diverse expertise in key areas we have identified multiplexed Process Analytical Technology (PAT) to provide the required rapid data for modelling the freeze-drying process. Such coupled PAT sensor technology will enable scrutiny and control of batch freeze-drying and enable future continuous freeze-drying processes. Anticipated CO2 savings are in the order of 700 tonnes per newly developed product, achieved by reduced development cycles and increased production efficiencies in the order of 1 per cent. This is equivalent to savings of CO2 emissions of 300 tonnes per year per freeze-dryer.

This innovative multiplexed approach offers insight potential for in-depth analysis of factors impacting batch manufacturing freeze-drying efficiency. It further affords the opportunity to enhance process understanding of the freezing and drying stages to de-risk the deployment of new continuous manufacturing techniques, and ultimately maximise their efficiency and sustainability.