title: Investigation of Air-Liquid Interface Rings in Buffer Preparation Vessels: the Role of Slip Agents.
abstract: Air-liquid interface rings were observed on the side walls of stainless steel buffer vessels after certain downstream buffer preparations. Those rings were resistant to regular cleaning-in-place procedures but could be removed by manual means. To investigate the root cause of this issue, multiple analytical techniques, including liquid chromatography with tandem mass spectrometry detection (LC-MS/MS), high-resolution accurate mass liquid chromatography with mass spectrometry, nuclear magnetic resonance, Fourier transform infrared spectroscopy, and scanning electron microscopy with energy-dispersive X-ray spectroscopy have been employed to characterize the chemical composition of air-liquid interface rings. The main component of air-liquid interface rings was determined to be slip agents, and the origin of the slip agents can be traced back to their presence on raw material packaging liners. Slip agents are commonly used in plastic industry as additives to reduce the coefficient of friction during the manufacturing process of thin films. To mitigate this air-liquid interface ring issue, an alternate liner with low slip agent was identified and implemented with minimal additional cost. We have also proactively tested the packaging liners of other raw materials currently used in our downstream buffer preparation to ensure slip agent levels are appropriate.
  Air-liquid interface rings were observed on the side walls of stainless steel buffer vessels after certain downstream buffer preparations. To investigate the root cause of this issue, multiple analytical techniques have been employed to characterize the chemical composition of air-liquid interface rings. The main components of air-liquid interface rings were determined to be slip agents, which are common additives used in the manufacturing process of thin films. The origin of the slip agents can be traced back to their presence on certain raw material packaging liners. To mitigate this air-liquid interface ring issue, an alternate liner with low slip agent was identified and implemented.
authors.affiliation: Manufacturing Sciences & Technology, Bristol-Myers Squibb, Devens, MA; ting.shi@bms.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Shi
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb, New Brunswick, NJ;
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.affiliation: Manufacturing Sciences & Technology, Bristol-Myers Squibb, Devens, MA;
authors.forename: Donald W
authors.initials: DW
authors.lastname: Kessler
authors.affiliation: Manufacturing Sciences & Technology, Bristol-Myers Squibb, Devens, MA;
authors.forename: Nuria
authors.initials: N
authors.lastname: De Mas
authors.affiliation: Global Quality Operations, Bristol-Myers Squibb, East Syracuse, NY;
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Weaver
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb, New Brunswick, NJ;
authors.forename: Charles
authors.initials: C
authors.lastname: Pathirana
authors.affiliation: Global Quality Operations, Bristol-Myers Squibb, East Syracuse, NY;
authors.forename: Russell D
authors.initials: RD
authors.lastname: Martin
authors.affiliation: Manufacturing Sciences & Technology, Bristol-Myers Squibb, East Syracuse, NY; and.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Mackin
authors.affiliation: Global Procurement Biologics Sourcing, Bristol-Myers Squibb, Devens, MA.
authors.forename: Michael
authors.initials: M
authors.lastname: Casati
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb, New Brunswick, NJ;
authors.forename: Scott A
authors.initials: SA
authors.lastname: Miller
authors.affiliation: Manufacturing Sciences & Technology, Bristol-Myers Squibb, Devens, MA;
authors.forename: Itzcoatl A
authors.initials: IA
authors.lastname: Pla
mesh_terms: D002021:Buffers; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods; D004349:Drug Packaging / Q000295:instrumentation / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation / Q000379:methods; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis; D017550:Spectroscopy, Fourier Transform Infrared / Q000295:instrumentation / Q000379:methods; D013193:Stainless Steel; D013499:Surface Properties
chemical_list: D002021:Buffers; D004364:Pharmaceutical Preparations; D013193:Stainless Steel
keywords: Cleaning validation; Erucamide; Leachable; Raw material; Slip agent