title: Biologics formulation factors affecting metal leachables from stainless steel.
abstract: An area of increasing concern and scientific scrutiny is the potential contamination of drug products by leachables entering the product during manufacturing and storage. These contaminants may either have a direct safety impact on the patients or act indirectly through the alteration of the physicochemical properties of the product. In the case of biotherapeutics, trace amounts of metal contaminants can arise from various sources, but mainly from contact with stainless steel (ss). The effect of the various factors, buffer species, solution fill volume per unit contact surface area, metal chelators, and pH, on metal leachables from contact with ss over time were investigated individually. Three major metal leachables, iron, chromium, and nickel, were monitored by inductively coupled plasma-mass spectrometry because they are the major components of 316L ss. Iron was primarily used to evaluate the effect of each factor since it is the most abundant. It was observed that each studied factor exhibited its own effect on metal leachables from contact with ss. The effect of buffer species and pH exhibited temperature dependence over the studied temperature range. The metal leachables decreased with the increased fill volume (mL) per unit contact ss surface area (cm(2)) but a plateau was achieved at approximately 3 mL/cm(2). Metal chelators produced the strongest effect in facilitating metal leaching. In order to minimize the metal leachables and optimize biological product stability, each formulation factor must be evaluated for its impact, to balance its risk and benefit in achieving the target drug product shelf life.
authors.affiliation: BioTherapeutics Pharmaceutical Sciences, Global Biologics, Pfizer Inc, St. Louis, Missouri 63017, USA. shuxia.zhou@pfizer.com
authors.forename: Shuxia
authors.initials: S
authors.lastname: Zhou
authors.forename: Christian
authors.initials: C
authors.lastname: Schöneich
authors.forename: Satish K
authors.initials: SK
authors.lastname: Singh
mesh_terms: D001688:Biological Products / Q000737:chemistry*; D002021:Buffers; D002614:Chelating Agents; D002857:Chromium / Q000032:analysis*; D004339:Drug Compounding; D004340:Drug Contamination; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000032:analysis*; D008670:Metals / Q000737:chemistry; D009532:Nickel / Q000032:analysis*; D013193:Stainless Steel; D013499:Surface Properties
chemical_list: D001688:Biological Products; D002021:Buffers; D002614:Chelating Agents; D008670:Metals; D002857:Chromium; D013193:Stainless Steel; D009532:Nickel; D007501:Iron