Development of Protein-Like Reference Material for Semi-Quantitatively Monitoring Visible Proteinaceous Particles in Biotherapeutics

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 and non-proteinaceous material. While particles made of non-proteinaceous material are unacceptable in drug products, proteinaceous particles may be acceptable on a case-by-case basis if characterized and shown not to pose quality, efficacy, and 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 biotherapeutics 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 semi-quantitative 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 commonly used polystyrene microsphere standards and therefore could be a viable standard for visible proteinaceous particles. Such standards and the semi-quantitative method illustrated could be used effectively during development to non-destructively identify potential stability problems.