Scale-up and transfer of lyophilization processes remain very challenging tasks considering the technical challenges and the high cost of the process itself. The challenges in scale-up and transfer were discussed in the first part of this paper and include vial breakage during freezing at commercial scale, cake resistance differences between scales, impact of differences in refrigeration capacities, and geometry on the performance of dryers. The second part of this work discusses successful and unsuccessful practices in scale-up and transfer based on the experience of the authors. Regulatory aspects of scale-up and transfer of lyophilization processes were also outlined including a topic on the equivalency of dryers. Based on an analysis of challenges and a summary of best practices, recommendations on scale-up and transfer of lyophilization processes are given including projections on future directions in this area of the freeze drying field. Recommendations on the choice of residual vacuum in the vials were also provided for a wide range of vial capacities.

The freeze-drying process scale-up and transfer remain a complicated and non-uniform practice. We summarized inefficient and good practices in these papers and provided some practical advice. It was demonstrated that using the same process set points/times in laboratory and commercial scale dryers may lead to loss of product quality (collapse or vial breakage). The emerging modeling approach demonstrated practical advantages. However, the upfront generation of some input parameters (vial heat transfer coefficient, minimum controllable pressure, and maximum sublimation rate) is essential for model utilization. While the primary drying step can be transferred with a high degree of confidence (e.g., using modeling), and secondary drying is usually fairly straightforward, predicting potential changes in product behavior during freezing remains challenging.

This paper presents the findings of the National Fluoride Varnish Workshop in 2018 along with subsequent actions to scale-up the use of fluoride varnish nationally in Australia. The use of fluoride varnish programs to prevent dental caries in high-risk child populations is an evidence-based population health approach used internationally. Such programs have not been implemented at scale nationally in Australia. A National Fluoride Varnish Consensus Workshop was held in Sydney in November 2018 with an aim of sharing the current work in this area being undertaken by various Australian jurisdictions and seeking consensus on key actions to improve the scale-up nationally. Forty-four people attended the Workshop with oral health representatives from all Australian state and territory health departments, as well as the Australian Dental Association (ADA) at both NSW branch and Federal levels. There was strong support for further scale-up of fluoride varnish programs nationally and to see the wider use of having non-dental professionals apply the varnish. This case study identifies key actions required to ensure scale-up of systematic fluoride varnish programs as part of a strategic population oral health approach to preventing dental caries among high-risk children who may not routinely access dental care.