Aseptically safe and fast administration of freeze-dried drug products: application for emergency cases and tropical diseases

The handling of medications is a parkour wired with complications in the preparation, administration, and aseptic handling of drugs. We identified existing gaps, which show the need for a medication system that facilitates the safe medication preparation for patients while providing a system that minimizes exposure of drugs to healthcare professionals. The aim of this thesis was to find a transfer solution for lyophilizates, that enables the safe and fast preparation of an IV infusion in the absence of an aseptic environment.
It is generally assumed that low and middle income countries are more likely to have a higher prevalence for medication errors such as aseptic omissions, incorrect dose preparations or wrong administration rates. In our non‐systematic review we elucidate that common and frequent medication errors are observed in high income countries as well and are not only an issue of the respective health care system. Medication errors with the highest prevalence and severity were extracted from 24 observational studies and based on their number of mentions the five major medication error types were elaborated. Recommended strategies to mitigate errors such as “wrong mixing and wrong reconstitution” and “wrong administration rate” were then compared to potential technical solutions that could ultimately avoid these errors. Next to increased training efforts and the introduction of control systems, the usage of adapter systems and ready‐to‐use systems were identified to be the most beneficial technical solutions to prevent the occurrence of such medication errors. A technical solution superior in evading most of these was a system that combines diluent and drug product in one dual chamber infusion bag.
Lyophilizates are a promising vehicle to sustain long‐term stability of proteinaceous drugs especially monoclonal antibodies. The manufacturing of such lyophilizates is however time and energy consuming and less favored over the storage of proteinaceous drugs as liquid solutions. This study evaluated the possibility to manufacture lyophilizates outside of the common production and storage container, the glass vial. Several different container formats were assessed on their ability to decrease processing times while maintaining solid state properties found in drugs lyophilized in glass vials. Ultimately, subtractive and additive manufacturing techniques were used to generate three‐dimensional lattice structures i.e. scaffolds, that were able to process the lyophilized drug product outside of the final storage container. Achieving equivalent solid state properties found in glass vials, with greater batch homogeneity and a decrease of processing times by more than 50%.
Lyophilized drug products are commonly stored in glass vials and require an aseptic environment and accurate handling to compound the drug product with the correct diluent into a sterile intravenous infusion. This study investigated if the combined storage of a lyophilized drug product in the vicinity of the diluent is feasible and comparable to the stability of drug product stored in glass vials. Lyophilized drug products were therefore prepared in novel intermediate processing containers (i.e. scaffold structures) and transferred into two differently designed dual chamber bags. During an accelerated stability study, drug products as liquid and as lyophilizate in glass vials were challenged against lyophilized drug products in dual chamber bags. The results showed, that the storage is highly dependent on the material choice of the dual chamber bag. Limiting the transfer of water vapor towards the drug product by use of temporary aluminum shielding and intricate chamber separations led to stability results comparable to the storage of lyophilizates stored in glass vials. This presentation of lyophilizates in dual chamber bags would thus allow the immediate and aseptically safe preparation of intravenous infusions while allowing the storage of the drug product with the associated diluent.