Systems used to package therapeutic products (pharmaceuticals, biologics, dietary supplements and devices) may be constructed from plastic materials and components. The plastics used in packaging systems are composed of homologous polymers with a range of molecular weights and additives such as antioxidants, stabilizers, lubricants, plasticizers, colorants, and others. Tests outlined in USP <661> are required to qualify plastic container for use with pharmaceutical based products. Test procedures are based upon the specific type of plastic that the container is made from. Five USP plastics, High Density Polyethylene (HDPE), Low Density Polyethylene (LDPE), Polypropylene (PP), PET and PETG are specifically listed in the chapter.
Establishing the suitability of plastic packaging systems for therapeutic products involves multiple tests and testing procedures, including Material screening and Extractables and Leachables assessment of the commercial product. Material screening will characterize packaging system’s materials of construction to evaluate ingredients as probable extractables and potential leachables, facilitating the identification of materials that are suitable for use in packaging systems. Testing of the plastic materials of construction to establish that they are well characterized and suitable for use, specifically considering safety, in packaging systems, is within the scope of the chapters and is addressed in Plastic Materials of Construction <661.1>. Testing of packaging systems to establish that they are suited for their intended uses, specifically considering safety is addressed in Plastic Packaging Systems for Pharmaceutical Use <661.2>. A controlled extraction study designed to simulate the worst case leachables profile is termed a simulation study and is detailed in Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems <1663>. Product assessment is ideally conducted using the confirmed leachables found in the therapeutic product in the pharmaceutical packaging/delivery system intended for the commercial market (Detailed in Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems <1664>).
Note that USP <661.1> and USP <661.2> become official on May 1, 2020. Until May 20, 2020, USP <661> will be used if adoption of <661.1> and <661.2> is chosen. If early adoption of USP <661.1> and USP <661.2> is chosen, then USP <661> need not be followed.
In general, USP <661.1> and USP <661.2> provide more comprehensive data packages compared to USP <661> and they link closely with the philosophies of USP <1661>, <1663>, <1664> and <1664.1> and the discussions ongoing around USP <665> (Single Use Systems). USP <661.1> and USP <661.2> data packages provide a knowledge base to facilitate an appropriate evaluation for the selection of materials and ultimately facilitate a chemical risk assessment for pharmaceutical packaging.
<665> Polymeric Components and Systems Used in the Manufacturing of Pharmaceutical and Biopharmaceutical Drug
USP <665> (formerly drafted as <661.3>) emphasizes analysis of organic extractables and extractable metals in plastic manufacturing materials and components used in the conversion of raw starting materials into active pharmaceutical ingredients, biopharmaceutical drug substances, and drug products. This testing includes all polymeric materials involved in solution transfer and transport, mixing and reacting, storage, and processing. This chapter focuses on polymeric manufacturing materials, components, or systems, which should not release substances that accumulate in the pharmaceutical or biopharmaceutical product as process equipment-related leachables in quantities that could adversely affect product quality or the health of the patient. Guidance on the Chemical Safety Assessments was detailed in drafted <1665> guidance “Plastic Components and Systems Used to Manufacture Pharmaceutical Drug Products”.