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.