Monitoring of Visible Particles in Parenteral Products by Manual Visual Inspection-Reassessing Size Threshold and Other Particle Characteristics that Define Particle Visibility.

Visible particles are a critical quality attribute for parenteral products and must be monitored. A carefully designed, executed, and controlled drug product manufacturing process including a final 100 % visual inspection and appropriate end-product controls ensures that visible particles are consistently minimized and demonstrates that the injectable DP is practically free from visible particles. Visual inspection, albeit appearing as a simple analytical procedure, requires several technical and operational controls to ensure adequate performance. To gather new data on particle visibility and shed light on this decade-old challenge, a multi-company blinded visual inspection threshold study was conducted. A major goal of the study was visual assessment of several particle types of different sizes in small volume vials, as a challenging configuration for visual inspection, across 9 biopharmaceutical companies in order to determine the visibility limit. The study results provide key insights into limitations and challenges of visual inspection, namely, no universal visibility limit can be applied to all particle types as the detectability varies with particle type, number, and size. The study findings underscore the necessity of setting realistic expectations on size-based visibility limits in visual inspection, robust procedures for analyst training and qualification, and harmonization of guidelines globally.

Development of Protein-Like Reference Material for Semiquantitatively Monitoring Visible Proteinaceous Particles in Biopharmaceuticals.

Visible particles may potentially pose safety and efficacy concerns if inadvertently administered to patients; therefore, it is crucial to monitor and characterize these particles. These particles may be composed of proteinaceous or non-proteinaceous material. Although particles made of non-proteinaceous material are unacceptable in drug products, proteinaceous particles may be acceptable on a case-by-case basis if they are characterized and shown to not pose any quality, efficacy, or safety concerns. The focus of this manuscript is on the proteinaceous particles that may potentially form in some biopharmaceuticals. Monitoring and tracking proteinaceous particles in these biopharmaceuticals can be challenging, but a universal protein-like particle standard might be able to help. The aim of this work is to evaluate abraded ethylene tetrafluoroethylene (ETFE) as a visible protein-like particle standard and demonstrate a semiquantitative method to show how this surrogate can be used to effectively monitor proteinaceous particles during formulation and analytical development. Studies indicated that the ETFE particles in solution better mimic the appearance and behavior of protein particles than the commonly used polystyrene microsphere standards and therefore could be a viable standard for visible proteinaceous particles. Such standards and the semiquantitative method illustrated could be used effectively during development to nondestructively identify potential stability problems.LAY ABSTRACT: Routine visual inspection of protein biopharmaceuticals is crucial to ensure the quality and consistency of drug products. Visible particles may potentially pose safety and efficacy concerns if administered to patients; therefore, it is important to monitor and to minimize them as much as possible. Visible proteinaceous particles, composed of aggregated protein in biopharmaceuticals, may be acceptable on a case-by-case basis if they are characterized and shown not to pose any quality, efficacy, or safety concerns. Monitoring and tracking these visible proteinaceous particles are challenging and could be aided by the use of a universal protein-like particle standard. In this work, a new visible protein-like particle surrogate made of ethylene tetrafluoroethylene (ETFE) will be introduced, and its use will be explored by developing a semiquantitative method to monitor proteinaceous particles in protein products. These studies show that ETFE particles possess desirable traits to become a viable protein-like particle standard that could be used during formulation development and to nondestructively identify potential stability problems.

Perceived benefits and challenges of repeated exposure to high fidelity simulation experiences of first degree accelerated bachelor nursing students.

This study explored perceptions of first-degree entry-level accelerated bachelor nursing students regarding benefits and challenges of exposure to multiple high fidelity simulation (HFS) scenarios, which has not been studied to date. These perceptions conformed to some research findings among Associate Degree, traditional non-accelerated, and second-degree accelerated Bachelor of Science in Nursing (BSN) students faced with one to two simulations. However, first-degree accelerated BSN students faced with multiple complex simulations perceived improvements on all outcomes, including critical thinking, confidence, competence, and theory-practice integration. On the negative side, some reported feeling overwhelmed by the multiple HFS scenarios. Evidence from this study supports HFS as an effective teaching and learning method for nursing students, along with valuable implications for many other fields.