Part I: Significant reduction of lyophilization process times by using novel matrix based scaffolds

Abstract

To improve the long-term stability of drugs with limited stability (e.g., biologicals such as monoclonal antibodies, antibody drug conjugates or peptides), some pharmaceuticals endure a lengthy and cost-intensive process called lyophilization. While the shelf life of lyophilized drugs may be prolonged compared to their liquid form, the drawbacks come in the form of intensified manufacturing, preparation, and dosing efforts. The use of glass vials as the primary container unit for lyophilized products hinders their complication-free, fast and flexible use, as they require a skilled healthcare professional and an aseptic environment in which to prepare them. The feasibility of substituting glass vials with novel container designs offering the complete transfer of the lyophilizate cake into modern administration devices, while reducing the economic footprint of the lyophilization process, was investigated. The lyophilization process of a monoclonal antibody solution was studied by assessing primary drying conditions, homogeneity of the drying process, and critical quality attributes after successful lyophilization. The creation of novel container designs utilized vacuum-forming to generate confined containers with removable bottoms and rapid prototyping, including subtractive and additive manufacturing methods, to generate porous 3D structures for drug housing. The novel container designs generated lyophilizates twice as fast and achieved a threefold faster reconstitution compared to their vial counterparts, without adaptation of the processing conditions. We conclude that the use of intermediate process containers offers significant relief for healthcare professionals in terms of reduced probability of handling errors, while drug manufacturers benefit from the accelerated processing times, increased batch homogeneity, and sustainability.