As outlined in USP 1663 “Assessment of Extractables” and USP 1664 “Assessment of Leachables associated with Pharmaceutical Packaging & Delivery Systems”, the primary purpose of these types of studies is the identification of any chemicals derived from the interaction of the drug product with the various container system components that could deleteriously impact overall drug efficacy or patient safety.
USP 1663 Extractables studies are designed to identify “substances” in a container closure system that can be “extracted” or pulled out of the components under conditions of stress. Typical stress factors used in the testing process include various chemical solvents and accelerated temperatures. Any substances “pulled out” of a material are further evaluated with a toxicological assessment to define the hazard level of the chemical substance to the drug product.
As defined under USP 1664, Leachables are substances, or chemicals, that come out, or “leach” from, the package system components under normal use conditions. As clearly stated in the USP “a scientifically sound leachable assessment is important to manufacturers and their various suppliers primarily as a means of establishing the suitability for use of pharmaceutical packaging systems.”
The FDA has outlined clear and distinct regulatory guidelines for E&L requirements. Understanding the chemical interactions between drug products and their package system materials of construction is a critical requirement. While USP 661.1 and USP 661.2 provide a basic extraction profile and are required for routine qualification, in many cases these may not be enough to satisfy E&L regulatory requirements for complex product and unique package system interactions. A comprehensive E&L program can and will include method development, method validation, materials characterization, impurity identification and elemental impurities analysis. A toxicological assessment also plays a crucial role in determining a safety profile score. A variety of laboratory instrumental techniques may also be used and may include HPLC, LC.MC, ICP, NMR, GC/MS.
The CS Analytical Teams has coupled their years of container qualification experience with an Extractable & Leachable partner to offer full-service E&L studies that meet all regulatory requirements inclusive of the TOX Assessment for extracted compounds. This seamless approach enables clients to meet all routine and complex container and package system qualification requirements under one clearly defined program. All work is always performed to strict cGMP quality levels under FDA guidelines.