Impact of Extractables/Leachables from Filter Materials on the Stability of Protein-Based Pharmaceutical Products

Abstract

AbstractThe manufacturing of biopharmaceutical drug solutions can involve close contact with various polymeric components, including common filter membranes. Potential leachable substances from filters may interact with the protein and thereby increase the structural damage and aggregation. The main aim of the study deals with the assessment of extractable and leachable (E/L) from different filters and the potential effect of E/Ls on protein (human granulocyte-colony stimulating factor (rh-GCSF) stability. The present study examines the E/L profile of five different polymeric filter membranes using various chromatographic techniques including LC–MS and GC–MS. In order to investigate their effect on protein stability, G-CSF (human granulocyte colony-stimulating factor) formulations were spiked with filter leachable stock solutions at two different pH levels. The spiked formulations were further analyzed with respect to their aggregation behavior. The results demonstrated a higher E/L content in the case of polyamide (PA), polycarbonate (PC), and polyethersulfone (PES) filters as compared to the polytetrafluoroethylene (PTFE) and regenerative cellulose (RC) filter materials. The E/L from RC and PES was found surface-active, whereas E/L from PA and RC significantly altered the particle size/structure resulting in the aggregation of proteins. Furthermore, bisphenol A was found to be one of the E/L substances from PC filters and can impose significant health problems when administered along with pharmaceutical products. The present study reports a qualitative rank ordering of the filter membranes in terms of their propensity to generate E/Ls and thus can be helpful in selecting a suitable membrane filter.