What is USP 661?
USP <661> refers to a set of analytical standards defined by the U.S. Pharmacopeia (USP) to help ensure the safety of a variety of health-related products composed of and/or packaged in plastic containers. These products include pharmaceuticals, biologics, dietary supplements, and devices. The polymers outlined in the USP <661> subchapters include high-density polyethylene (HDPE), low-density polyethylene (LDPE), polypropylene (PP), polyethylene terephthalate (PET), polyethylene terephthalate G (PETG), and plasticized polyvinyl chloride (PVC). In order for plastic packaging to be approved for use with an FDA-approved therapeutic product, data must show that the material/packaging conforms to USP <661> standards and performance criteria.
In 2016, the USP expanded the analytical standards in chapter <661> to further support packaging safety. USP <661.1>, entitled ‘PLASTIC MATERIALS OF CONSTRUCTION’, introduces more rigorous standards and testing to demonstrate that polymer raw material is well-characterized and suitable for its intended use. USP <661.2>, entitled ‘PLASTIC PACKAGING SYSTEMS FOR PHARMACEUTICAL USE’, focuses on the products’ full polymer packaging system. This includes the primary packaging that comes in contact with the pharmaceutical product as well as any relevant secondary packaging. Through our considerable experience in regulatory compliant polymer analysis, we are also able to provide guidance on the Chemical Safety Assessments required in the expanded guidance chapters 〈1663〉 “Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems” and 〈1664〉 “Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems”.
Packaging Component Experience
What is USP 665?
USP <665> (formerly drafted as <661.3>) titled ‘POLYMERIC COMPONENTS AND SYSTEMS USED IN THE MANUFACTURING OF PHARMACEUTICAL AND BIOPHARMACEUTICAL DRUG PRODUCTS’ 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 (APIs), biopharmaceutical drug substances (DS), and drug products (DP). The polymers used in these manufacturing systems may contain additives of concern such as antioxidants, stabilizers, lubricants, plasticizers, and colorants. This testing encompasses all polymeric materials involved in solution transfer and transport, mixing and reacting, storage, and processing including:
- Tubing and connectors
- Tank liners and mixing bags
- Raw material containers
- Production reagents
- Filters and chromatography columns
As an extension of our comprehensive extractable experience and knowledge, we are also able to provide guidance on the Chemical Safety Assessments required in drafted <1665> guidance “Plastic Components and Systems Used to Manufacture Pharmaceutical Drug Products”.
USP <661> and <665>Testing at EKG Labs
EKG Labs supports USP <661> (for legacy and delayed 661.X implementation), <661.1>, <661.2>, and <665> analytical testing for pharmaceutical, combination product, and medical device industries. Our experience working with polymer materials and active ingredients uniquely positions us an industry leader in therapeutic product manufacturing and packaging testing. We understand the unique interactions that are possible when components come in contact with one another. EKG Labs will work to identify any impurities or degradants associated with the material contact and, if necessary, will help to identify alternative manufacturing or packaging materials.
Analytical Techniques at EKG Labs
- Infrared Spectroscopy
- Differential Scanning Calorimetry
- Heavy Metals
- Nonvolatile Residue
- Total Organic Carbon
- Extractable Metals