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Biopharmaceuticals are complex biological molecules that require careful storage and handling to ensure medication integrity. In this study, a work system analysis of real-world protein drug (PD) handling was performed with the following goals: identify main barriers and facilitators for successful adherence to accepted recommendations in PD handling, analyse differences in two organizations, and define a Best Current Practice in the real-life handling of PDs based on the results of the work system analysis. Observational study was held in two university hospitals in Spain and Sweden. Based on the Systems Engineering Initiative for Patient Safety (SEIPS) model, the tools chosen were: the PETT scan, in order to indicate the presence of barriers or facilitators for the PETT components (People, Environment, Tools, Tasks); the Tasks and tools matrices to construct a checklist to record direct observations during the real-life handling of biopharmaceuticals, and the Journey map to depict the work process. Observations were performed between March and November 2022. Each episode of direct observation included a single protein drug in some point of the supply chain and considered all the elements in the work system. Based on the results of the work system analysis and the literature review, the authors propose a list of items which could be assumed as Best Current Practice for PDs handling in hospitals. There were a total of 34 observations involving 19 PDs. Regarding People involved in the work process, there was a diversity of professionals with different previous training and knowledge, leading to an information gap. With respect to Environment, some structural and organizational differences between hospitals lead to risks related to the time exposure of PDs to room temperature and mechanical stress. Some differences also existed in the Tools and Tasks involved in the process, being especially relevant to the lack of compatibility information of PDs with new technologies, such as pneumatic tube system, robotic reconstitution, or closed-system transfer devices. Finally, 15 suggestions for best current practice are proposed. Main barriers found for compliance with accepted recommendations were related to the information gap detected in professionals involved in the handling of protein drugs, unmonitored temperature, and the lack of compatibility information of protein drugs with some new technologies. By applying a Human Factors and Systems Engineering Approach, the comparison of two European hospitals has led to a suggested list of Best Current Practices in the handling of protein drugs in a hospital. [ABSTRACT FROM AUTHOR]

Freeze drying is a commonly used method for preserving probiotic bacteria and live biotherapeutic products. Before drying, the bacterial cells are formulated with a lyoprotectant, and the design of these two process steps are crucial to achieve a high-quality product. There are several factors that may affect the biological and physicochemical properties of the freeze-dried cells and we have used a Design of Experiment approach to investigate the effects of formulation and freeze-drying parameters on properties and performance of Limosilactobacillus reuteri R2LC. The biological characteristics of the dried bacteria were evaluated by measuring cell survival, metabolic activity and stability, and physicochemical characteristics were studied using visual inspection, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and analysis of residual moisture content and bacterial aggregation. A comparison between the lyoprotectants trehalose and sucrose showed that the latter gave better freeze-drying survival, metabolic activity, and storage stability. We also want to highlight that there was a correlation between bacterial concentration, metabolic activity, and aggregation of bacteria, where a higher concentration (1010 CFU/mL) resulted in both higher metabolic activity and aggregation. Several other process and formulation factors affected both the biological and physicochemical properties of freeze-dried L. reuteri R2LC and it could be concluded that care must be taken to develop a production method that generates a product with high and consistent quality. These results may, or may not, be strain specific. [ABSTRACT FROM AUTHOR]

Although unfolding of protein in the liquid state is relatively well studied, its mechanisms in the solid state, are much less understood. We evaluated the reversibility of thermal unfolding of lysozyme with respect to the water content using a combination of thermodynamic and structural techniques such as differential scanning calorimetry, synchrotron small and wide-angle X-ray scattering (SWAXS) and Raman spectroscopy. Analysis of the endothermic thermal transition obtained by DSC scans showed three distinct unfolding behaviors at different water contents. Using SWAXS and Raman spectroscopy, we investigated reversibility of the unfolding for each hydration regime for various structural levels including overall molecular shape, secondary structure, hydrophobic and hydrogen bonding interactions. In the substantially dehydrated state below 37 wt% of water the unfolding is an irreversible process and can be described by a kinetic approach; above 60 wt% the process is reversible, and the thermodynamic equilibrium approach is applied. In the intermediate range of water contents between 37 wt% and 60 wt%, the system is phase separated and the thermal denaturation involves two processes: melting of protein crystals and unfolding of protein molecules. A phase diagram of thermal unfolding/denaturation in lysozyme - water system was constructed based on the experimental data., Competing Interests: We declare no conflict of interest., (© 2021 The Authors.)