title: The Use of TOC Reconciliation as a Means of Establishing the Degree to Which Chromatographic Screening of Plastic Material Extracts for Organic Extractables Is Complete.
abstract: Extracts of plastic packaging, manufacturing, and delivery systems (or their materials of construction) are analyzed by chromatographic methods to establish the system's extractables profile. The testing strategy consists of multiple orthogonal chromatographic methods, for example, gas and liquid chromatography with multiple detection strategies. Although this orthogonal testing strategy is comprehensive, it is not necessarily complete and members of the extractables profile can elude detection and/or accurate identification/quantification. Because the chromatographic methods rarely indicate that some extractables have been missed, another means of assessing the completeness of the profiling activity must be established. If the extracts are aqueous and contain no organic additives (e.g., pH buffers), then they can be analyzed for their total organic carbon content (TOC). Additionally, the TOC of an extract can be calculated based on the extractables revealed by the screening analyses. The measured and calculated TOC can be reconciled to establish the completeness and accuracy of the extractables profile. If the reconciliation is poor, then the profile is either incomplete or inaccurate and additional testing is needed to establish the complete and accurate profile. Ten test materials and components of systems were extracted and their extracts characterized for organic extractables using typical screening procedures. Measured and calculated TOC was reconciled to establish the completeness of the revealed extractables profile. When the TOC reconciliation was incomplete, the profiling was augmented with additional analytical testing to reveal the missing members of the organic extractables profile. This process is illustrated via two case studies involving aqueous extracts of sterile filters.
  Plastic materials and systems used to manufacture, contain, store, and deliver pharmaceutical products are extracted and the extracts analyzed to establish the materials' (or systems') organic extractables profile. Such testing typically consists of multiple chromatographic approaches whose differences help to ensure that all organic extractables are revealed, measured, and identified. Nevertheless, this rigorous screening process is not infallible and certain organic extractables may elude detection. If the extraction medium is aqueous, the process of total organic carbon (TOC) reconciliation is proposed as a means of establishing when some organic extractables elude detection. In the reconciliation, the TOC of the extracts is both directly measured and calculated from the chromatographic data. The measured and calculated TOC is compared (or reconciled), and the degree of reconciliation is an indication of the completeness and accuracy of the organic extractables profiling. If the reconciliation is poor, then the extractables profile is either incomplete or inaccurate and additional testing must be performed to establish the complete and accurate profile. This article demonstrates the TOC reconciliation process by considering aqueous extracts of 10 different test articles. Incomplete reconciliations were augmented with additional testing to produce a more complete TOC reconciliation.
authors.affiliation: Baxter Healthcare Corporation, Round Lake, IL and dennis_jenke@baxter.com.
authors.forename: Dennis
authors.initials: D
authors.lastname: Jenke
authors.affiliation: Baxter Healthcare Corporation, Round Lake, IL and.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Couch
authors.affiliation: VR Analytical, LLC, Bend, OR.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Robinson
authors.affiliation: VR Analytical, LLC, Bend, OR.
authors.forename: Trent J
authors.initials: TJ
authors.lastname: Volz
authors.affiliation: VR Analytical, LLC, Bend, OR.
authors.forename: Raymond H
authors.initials: RH
authors.lastname: Colton
mesh_terms: D002244:Carbon / Q000032:analysis*; D002845:Chromatography / Q000379:methods* / Q000592:standards; D004340:Drug Contamination / Q000517:prevention & control*; D016503:Drug Delivery Systems; D004349:Drug Packaging; D009930:Organic Chemicals / Q000032:analysis*; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000592:standards; D010969:Plastics / Q000737:chemistry*
chemical_list: D009930:Organic Chemicals; D004364:Pharmaceutical Preparations; D010969:Plastics; D002244:Carbon
keywords: Extractables; Manufacturing systems; Medical devices; Packaging systems; Plastics; Polymers; Reconciliation; Total organic carbon (TOC)