title: Particle shedding from peristaltic pump tubing in biopharmaceutical drug product manufacturing.
abstract: In a typical manufacturing setup for biopharmaceutical drug products, the fill and dosing pump is placed after the final sterile filtration unit in order to ensure adequate dispensing accuracy and avoid backpressure peaks. Given the sensitivity of protein molecules, peristaltic pumps are often preferred over piston pumps. However, particles may be shed from the silicone tubing employed. In this study, particle shedding and a potential turbidity increase during peristaltic pumping of water and buffer were investigated using three types of commercially available silicone tubing. In the recirculates, mainly particles of around 200 nm next to a very small fraction of particles in the lower micrometer range were found. Using 3D laser scanning microscopy, surface roughness of the inner tubing surface was found to be a determining factor for particle shedding from silicone tubing. As the propensity toward particle shedding varied between tubing types and also cannot be concluded from manufacturer's specifications, individual testing with the presented methods is recommended during tubing qualification. Choosing low abrasive tubing can help to further minimize the very low particle counts to be expected in pharmaceutical drug products.
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität, München, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Saller
authors.forename: Julia
authors.initials: J
authors.lastname: Matilainen
authors.forename: Ulla
authors.initials: U
authors.lastname: Grauschopf
authors.forename: Karoline
authors.initials: K
authors.lastname: Bechtold-Peters
authors.forename: Hanns-Christian
authors.initials: HC
authors.lastname: Mahler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Friess
mesh_terms: D001702:Biopharmaceutics / Q000295:instrumentation*; D002021:Buffers; D004340:Drug Contamination; D004867:Equipment Design; D007260:Infusion Pumps; D018613:Microscopy, Confocal; D009391:Nephelometry and Turbidimetry; D018570:Risk Assessment; D012828:Silicones / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000295:instrumentation*; D014867:Water / Q000737:chemistry
chemical_list: D002021:Buffers; D012828:Silicones; D014867:Water
keywords: filling; light scattering (dynamic); microscopy; morphology; nephelometry; particle size; polymers; processing; unit operations