title: Influence of particle shedding from silicone tubing on antibody stability.
abstract: OBJECTIVE
  Peristaltic pumps are increasingly employed during fill & finish operations of a biopharmaceutical drug, due to sensitivity of many biological products to rotary piston pump-related stresses. Yet, possibly also unit operations using peristaltic pumps may shed particulates into the final product due to abrasion from the employed tubing. It was the aim of this study to elucidate the potential influence of particles shed from peristaltic pump tubing on the stability of a drug product.
  
  
  METHODS
  Spiking solutions containing shed silicone particles were prepared via peristaltic pumping of placebo under recirculating conditions and subsequently characterized. Two formulated antibodies were spiked with two realistic, but worst-case levels of particles and a 6-month accelerated stability study with storage at 2-8, 25 and 40°C were conducted.
  
  
  RESULTS
  Regarding the formation of aggregates and fragments, both mAbs degraded at their typically expected rates and no additional impact of spiked particles was observed. No changes were discerned however in turbidity, subvisible and visible particle assessments. Flow imaging data for one of the mAb formulations with spiked particles suggested limited colloidal stability of shed particles as indicated by a similar increase in spiked placebo.
  
  
  CONCLUSIONS
  Shed silicone particles from peristaltic pump tubing are assumed to not impair drug product stability.
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Saller
authors.affiliation: F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe, Basel, Switzerland.
authors.forename: Constanze
authors.initials: C
authors.lastname: Hediger
authors.affiliation: F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe, Basel, Switzerland.
authors.forename: Julia
authors.initials: J
authors.lastname: Matilainen
authors.affiliation: F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe, Basel, Switzerland.
authors.forename: Ulla
authors.initials: U
authors.lastname: Grauschopf
authors.affiliation: F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe, Basel, Switzerland.
authors.forename: Karoline
authors.initials: K
authors.lastname: Bechtold-Peters
authors.affiliation: F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe, Basel, Switzerland.
authors.forename: Hanns-Christian
authors.initials: HC
authors.lastname: Mahler
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Friess
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D004339:Drug Compounding / Q000295:instrumentation; D004345:Drug Industry / Q000295:instrumentation; D004355:Drug Stability; D004356:Drug Storage; D004867:Equipment Design; D012828:Silicones / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000295:instrumentation*; D013696:Temperature
chemical_list: D000911:Antibodies, Monoclonal; D012828:Silicones
keywords: fill & finish; particle analytics; protein stability; silicone tubing