title: Pharmaceutical feasibility of sub-visible particle analysis in parenterals with reduced volume light obscuration methods.
abstract: The draft for a new United States Pharmacopoeia (USP) monograph {787} "Sub-visible Particulate Matter in Therapeutic Protein Injections" describes the analysis of sub-visible particles by light obscuration at much lower sample volumes as so far required by the European Pharmacopoeia (Ph. Eur.) and the USP for parenterals in general. Our aim was to show the feasibility of minimizing the sample expenditure required for light obscuration similar to the new USP settings for standards and pharmaceutically relevant samples (both proteins and small molecules), without compromising the data quality. The light obscuration method was downscaled from >20 ml volume as so far specified in Ph. Eur./USP to 1 ml total sample volume. Comparable results for the particle concentration in all tested size classes were obtained with both methods for polystyrene standards, stressed BSA solutions, recombinant human IgG1 formulations, and pantoprazol i.v. solution. An additional advantage of the low volume method is the possibility to detect vial-to-vial variations, which are leveled out when pooling several vials to achieve sufficient volume for the Ph. Eur./USP method. This is in particular important for biotech products where not only the general quality aspect, but also aggregate formation of the drug substance is monitored by light obscuration.
authors: Coriolis Pharma, Biopharmaceutical Research and Development, Martinsried, Germany. Electronic address: Andrea.Hawe@coriolis-pharma.com.
authors: Andrea
authors: A
authors: Hawe
authors: Frank
authors: F
authors: Schaubhut
authors: Raimund
authors: R
authors: Geidobler
authors: Michael
authors: M
authors: Wiggenhorn
authors: Wolfgang
authors: W
authors: Friess
authors: Markus
authors: M
authors: Rast
authors: Christian
authors: C
authors: de Muynck
authors: Gerhard
authors: G
authors: Winter
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000737:chemistry; D000818:Animals; D002417:Cattle; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004340:Drug Contamination; D005240:Feasibility Studies; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D007263:Infusions, Parenteral; D008027:Light; D000077402:Pantoprazole; D010316:Particle Size; D019999:Pharmaceutical Solutions / Q000032:analysis*; D011137:Polystyrenes / Q000737:chemistry; D011506:Proteins / Q000737:chemistry; D015203:Reproducibility of Results; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D007074:Immunoglobulin G; D019999:Pharmaceutical Solutions; D011137:Polystyrenes; D011506:Proteins; D012710:Serum Albumin, Bovine; D000077402:Pantoprazole
keywords: Aggregation; Light obscuration; Parenterals; Protein formulation; Quality control; Sub-visible particles