title: Development and Justification of a Risk Evaluation Matrix To Guide Chemical Testing Necessary To Select and Qualify Plastic Components Used in Production Systems for Pharmaceutical Products.
abstract: An accelerating trend in the pharmaceutical industry is the use of plastic components in systems used to produce an active pharmaceutical ingredient or a finished drug product. If the active pharmaceutical ingredient, the finished drug product, or any solution used to generate them (for example, a process stream such as media, buffers, eluents, and the like) is contacted by a plastic component at any time during the production process, substances leached from the component may accumulate in the active pharmaceutical ingredient or finished drug product, affecting its safety and/or efficacy. In this article the author develops and justifies a semi-quantitative risk evaluation matrix that is used to determine the amount and rigor of component testing necessary and appropriate to establish that the component is chemically suitable for its intended use. By considering key properties of the component, the contact medium, the contact conditions, and the active pharmaceutical ingredient's or finished drug product's clinical conditions of use, use of the risk evaluation matrix produces a risk score whose magnitude reflects the accumulated risk that the component will interact with the contact solution to such an extent that component-related extractables will accumulate in the active pharmaceutical ingredient or finished drug product as leachables at levels sufficiently high to adversely affect user safety. The magnitude of the risk score establishes the amount and rigor of the testing that is required to select and qualify the component, and such testing is broadly grouped into three categories: baseline assessment, general testing, and full testing (extractables profiling).
  
  
  
  Production suites used to generate pharmaceuticals can include plastic components. It is possible that substances in the components could leach into manufacturing solutions and accumulate in the pharmaceutical product. In this article the author develops and justifies a semi-quantitative risk evaluation matrix that can be used to determine the amount and rigor of component testing that may be necessary and appropriate to establish that the component is suitable for its intended use. Use of the risk evaluation matrix allows a user of a component to determine the type and amount of testing that should be performed to establish the patient safety risk associated with using that component in order to manufacture an active pharmaceutical ingredient or a finished drug product.
authors.affiliation: Baxter R&D, Baxter Healthcare Corporation, 25122 West Illinois Route 120, Round Lake, IL 60073 dennis_jenke@baxter.com.
authors.forename: Dennis
authors.initials: D
authors.lastname: Jenke
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004340:Drug Contamination / Q000517:prevention & control*; D004345:Drug Industry; D004867:Equipment Design; D004364:Pharmaceutical Preparations / Q000592:standards*; D010969:Plastics / Q000737:chemistry*; D018570:Risk Assessment / Q000379:methods
chemical_list: D004364:Pharmaceutical Preparations; D010969:Plastics
keywords: Extractables; Production systems; Risk assessment; Risk-based approach; Single-use systems