Multi-attribute Raman spectroscopy (MARS) for monitoring product quality attributes in formulated monoclonal antibody therapeutics.

Rapid release of biopharmaceutical products enables a more efficient drug manufacturing process. Multi-attribute methods that target several product quality attributes (PQAs) at one time are an essential pillar of the rapid-release strategy. The novel, high-throughput, and nondestructive multi-attribute Raman spectroscopy (MARS) method combines Raman spectroscopy, design of experiments, and multivariate data analysis (MVDA). MARS allows the measurement of multiple PQAs for formulated protein therapeutics without sample preparation from a single spectroscopic scan. Variable importance in projection analysis is used to associate the chemical and spectral basis of targeted PQAs, which assists in model interpretation and selection. This study shows the feasibility of MARS for the measurement of both protein purity-related and formulation-related PQAs; measurements of protein concentration, osmolality, and some formulation additives were achieved by a generic multiproduct model for various protein products containing the same formulation components. MARS demonstrates the potential to be a powerful methodology to improve the efficiency of biopharmaceutical development and manufacturing, as it features fast turnaround time, good robustness, less human intervention, and potential for automation.

Perioperative antimicrobial decision making: Focused ethnography study in orthopedic and cardiothoracic surgeries in an Australian hospital.

OBJECTIVE: Antimicrobial use in the surgical setting is common and frequently inappropriate. Understanding the behavioral context of antimicrobial use is a critical step to developing stewardship programs. DESIGN: In this study, we employed qualitative methodologies to describe the phenomenon of antimicrobial use in 2 surgical units: orthopedic surgery and cardiothoracic surgery. SETTING: This study was conducted at a public, quaternary, university-affiliated hospital. PARTICIPANTS: Healthcare professionals from the 2 surgical unit teams participated in the study. METHODS: We used focused ethnographic and face-to-face semi-structured interviews to observe antimicrobial decision-making behaviors across the patient's journey from the preadmission clinic to the operating room to the postoperative ward. RESULTS: We identified 4 key themes influencing decision making in the surgical setting. Compartmentalized communication (theme 1) was observed with demarcated roles and defined pathways for communication (theme 2). Antimicrobial decisions in the operating room were driven by the most senior members of the team. These decisions, however, were delegated to more junior members of staff in the ward and clinic environment (theme 3). Throughout the patient's journey, communication with the patient about antimicrobial use was limited (theme 4). CONCLUSIONS: Approaches to decision making in surgery are highly structured. Although this structure appears to facilitate smooth flow of responsibility, more junior members of the staff may be disempowered. In addition, opportunities for shared decision making with patients were limited. Antimicrobial stewardship programs need to recognize the hierarchal structure as well as opportunities to engage the patient in shared decision making.