Are the 661.1 and 661.2 Chapters now effective and required?
The short answer is no. USP 661.1 and USP 661.2 becomes official on December 1, 2025 and until such time USP 661 still applies. However, as stated in the USP early adoption of 661.1 and 661.2 is encouraged early and if early adoption is chosen, then USP 661 does not need to be done. It is important to note that all packaging materials must meet USP 661.1 and 661.2 requirements after December 1, 2025 even if they had only met the requirements of USP 661 previously.
What is the key difference between USP 661.1 and 661.2?
USP 661.1 relates to a plastic material of construction used to manufacture a packaging system. It is best to think of this at the resin level. If your container is made of HDPE, the 661.1 testing is designed to test that specific resin. USP 661.2 relates to a packaging system as a whole and includes all components that make up that system. For example, the container, the closure, the dropper, the snap cap, etc. Collectively, USP 661.1 and 661.2 provide a comprehensive data package that will facilitate an appropriate evaluation for the correct selection of materials and protect patients more than would be possible with the current 661 test methods.
What are the expectations for biocompatibility testing?
USP 661.1 and 661.2 describes the biocompatibility testing requirements that are dependent on the dosage form, therefore knowledge of the end use is required. Oral and topical dosage forms do not require USP 87 Biological Reactivity Test, In Vitro. Testing for compliance to USP 661.1 or USP 661.2 for all other dosage forms require the 87 testing. USP 88 Biological Reactivity Tests, In Vivo is not directly referenced in these chapters. USP 87 does however note that materials that fail USP 87 should be further tested to USP 88 standards.
Is an Extractable and Leachables (E&L) study required?
E&L Testing is not a stated and specific requirement. As directed by the USP, a “Chemical Safety Assessment” is required for packaging systems as described in USP 661.2 that is “risk-based”. This risk-based assessment is based on the packaging system, its materials of construction, its components of construction, and the actual drug product it will hold. Where testing is needed as part of a chemical safety assessment, it must be based on sound and justifiable scientific principles which are outlined in USP 1663 and USP 1664.
How will one apply new chapters in the real world?
USP 661.1 and 661.2 can be applied depending on whether the end-user seeks to evaluate an individual plastic material or an entire packaging system. For example, let’s consider a package system that uses a High-Density Polyethylene (HDPE) bottle in conjunction with a Polypropylene (PP) closure. HDPE and PP resin used to develop this packaging system are considered well-characterized if they meet the USP requirements as outlined and required in the 661.1 chapter. The individual bottle (HDPE) would be tested, and the separate and individual closure (PP) would be tested. As a whole package system (bottle and closure combined, the USP661.2 would be required. As a simple rule, 661.1 applies to INDIVIDUAL COMPONENTS or plastic types and 661.2 applies to entire PACKAGE SYSTEMS.
Reasons to test to the new methods now and not wait for the December 2025 implementation date?
As clearly stated in these USP chapters, early adoption and use of these test methods is encouraged and acceptable. The CS analytical team of experts highly recommends the early adoption due to the following reasons.
- Risk: Plastic Packaging systems for pharmaceutical and their materials of construction currently qualified under USP661 for their intended use will be required to be requalified as per new standards December 1, 2025. Hence, you will need to perform these tests.
- The new test methods are more comprehensive and stringent. Currently materials in use may not meet the new testing specifications. It would be ideal to identify this now (2022) so that there is sufficient time to make changes or corrections while the material or package system still remain valid under current 661 requirements.
- Waiting to requalify materials and package systems until December 1, 2025 will require additional time for budgeting and allocation of resources that are expected to be more expensive in 2025/2026 than they are today.
The CS Analytical Team was one of the first in the contract laboratory market to devise and offer cGMP, FDA-registered services according to the new standards and are ready to leverage years of hands-on experience to devise test plans according to the specific product-package system in question to ensure all regulatory requirements are met. We have the knowledge, experience and facility to ensure that all USP container and package system test requirements are met for a wide variety of package types