Changes to USP 661: Regulations for Pharmaceutical Plastic Packaging
On 1 December 2025, the USP (United States Pharmacopeia) finally published the change that had long been taking shape in the field of pharmaceutical plastic packaging: chapter <661> ceases to be the “sole” reference and is reorganised into two independent chapters, <661.1> and <661.2>, with a considerably clearer division of objectives.
In practice, this means that the USP separates what was previously combined within a single chapter: on one hand, the evaluation of plastic material as a “material of construction” and, on the other, the evaluation of the finished packaging system and its suitability for containing a medicinal product.
The published information itself states that, as of 1 December 2025, chapter <661> “in its current form” becomes obsolete, and that the valid tests are henceforth those set out in <661.1> and <661.2>.
What is the difference between USP <661.1> and USP <661.2>?
Under this new structure, chapter <661.1> validates whether a plastic material (resin, formulation, or starting material) is characterised and appropriate from a pharmacopoeial standpoint. In other words, it focuses on “what” the plastic is and how it behaves as a material. Chapter <661.2>, by contrast, validates the finished container (the complete system that will hold the medicinal product) and considers it characterised and suitable for pharmaceutical use only if it is evaluated under this chapter:
| Test | USP <661> | USP <661.1> | USP <661.2> |
| Identification | Yes (both) | IR and/or DSC according to material | No |
| Heavy metals and non-volatile residue | Yes | IR and/or DSC according to material | No |
| Heavy metals (ICP) | Yes | Yes | No |
| Residue on ignition | No | No | No |
| Colour of extract | Yes | Yes | Yes |
| Clarity of extract | No | Yes (PET) | Yes (PET) |
| Ethylene glycol units | Yes (PET) | Yes (PET) | Yes (PET) |
| Absorbance (according to material) | No | No | Yes |
| Acidity / alkalinity (according to material) | No | Yes | Yes |
| Total organic carbon (according to material) | No | Yes | Yes |
| Functional test – spectral transmission (light-resistant containers) | No | n/a | Yes |
| Extractable metals (ICP) | No | According to material (<1661>, <232>, <233>) | According to material (<1661>, <232>, <233>) |
| Biological tests <87> / <88> | <87> and <88> | According to dosage form | According to dosage form |
| Additional biological tests (<1661>, <1663>, <1664>, <1664.1>) | No | Yes, according to use | Yes, according to use |
| Extractables and leachables | No | Yes | Yes |
| Analysis of additives, stabilisers, and residual solvents | No | Yes | Yes |
Impact on the pharmaceutical industry: which chapter to apply in each case
This distinction has very direct practical consequences for the industry. If a company wishes to evaluate the plastic material it intends to use for manufacturing a container (for example, prior to the conversion process), the reference text is now <661.1>. If what is required is to demonstrate that the finished container, as it will be used, is suitable for holding a medicinal product, the reference is <661.2>.
The separation into <661.1> and <661.2> requires demonstrating compliance with data and a complete documentary justification. Furthermore, the need to demonstrate container–drug compatibility is reinforced, taking into account the possible migration of substances from the material into the product (in the context of extractables and leachables) and evaluating it under representative conditions of use.
For this reason, in addition to testing, it is essential to manage information effectively throughout the supply chain. The aim is to ensure that every part of the chain has sufficient data to complete its own evaluation and address the points that cannot be resolved at earlier stages.
In conclusion, the division of <661> into <661.1> and <661.2> clarifies the framework: plastic materials and packaging systems are no longer evaluated as though they were the same, but rather according to differentiated requirements.
At AIMPLAS, we have a team of experts who can advise you on the technical and regulatory evaluation of your packaging systems — contact us!