Applying the Final Touches

By Frances L. DeGrazio, vice president, Marketing & Strategic Business Development, West Leachables are chemical entities that migrate under normal conditions from a container closure system and other packaging components under recommended conditions of product use and storage. Extractables, unlike leachables, are generated under extreme temperature and time conditions in the presence of an appropriate solvent (e.g., polar and non-polar organic solvents, purified water). Leachables are often a subset of extractables; however, they can also be derived by chemical modification (e.g. degradation) of extractables. Evaluation of extractables is considered an essential step in the accurate prediction of leachables, and in the selection of an adequate container closure system for a drug product. The interaction of the drug product, the packaging components, manufacturing process, product quality attributes and storage conditions (e.g., temperature and duration) is critical in determining an extractables/ leachables profile. Chemical leaching is often detected during product storage and rarely at the time of release. This emphasizes the need for comprehensive stability protocols that not only evaluate typical product quality attributes, but are also capable of detecting potential leachables. The potential impact of extractables on drug products is significant, especially with sensitive biopharmaceutical drug products that may contain extremely small amounts of active ingredient. Perhaps more important than these materials’ toxicology is their potential to elicit serious immunologic responses, even at minute dosages. Fluorocarbon film protects against extractables Fluorocarbon films provide a barrier to protect the drug product against extractables from the elastomeric material, thereby minimizing leachables. When applied to stoppers or plungers, fluorocarbon films significantly reduce adsorption of the drug onto the stopper, which is critical for maintaining the product’s potency and shelf-life. In addition, fluorocarbon films provide lubricity to enhance performance on pharmaceutical filling lines without the need for free silicone oil, a potential source of particulate contamination.