USP <661.1> and <661.2> are the two general chapters of the United States Pharmacopeia that define how to characterize plastic materials of construction and how to qualify plastic packaging systems for pharmaceutical use. Since December 1, 2025 the revised chapters are official and mandatory, and since February 1, 2026 the umbrella chapter <661> no longer contains test methods of its own: anyone still qualifying bottles, caps, blisters and HDPE containers «per USP <661>» with the legacy tests is citing a requirement that no longer exists in that form. This article covers what each chapter requires, how they divide the work and the findings that come up most often in audits.
USP <661.1> and <661.2>: the new architecture of chapter <661>
The suite works on two levels. <661.1> Plastic Materials of Construction operates at material level: the resin (HDPE, PP, PET, PVC and the other polymers covered by the chapter) must be well characterized and suitable for use in packaging components. <661.2> Plastic Packaging Systems for Pharmaceutical Use operates at system level: the finished packaging, with all its components, must be suited to its intended use with that product.
The revised chapter <661>, official since February 1, 2026, closes the loop: the legacy test methods and acceptance criteria have been removed, and compliance with <661> is demonstrated by applying the <661.1> tests, by meeting the <661.2> requirements, or both. Vendor information on materials and systems can support the suitability assessment, supplementing or replacing part of the testing. The informational chapter <1661> accompanies the suite and explains its scope and application from a patient-safety perspective.
Two dates matter. December 1, 2025: the revised <661.1> and <661.2> became official and their application is no longer an early-adoption choice. February 1, 2026: the rewritten <661> took effect, reduced to a pointer chapter. For anyone marketing in the US or claiming USP compliance in their dossiers, this pair of deadlines — both now behind us — defines the state of the art auditors and inspectors expect in 2026.
What USP <661.1> requires of materials of construction
For each plastic material the chapter structures characterization around four areas:
- Identity of the polymer (typically via IR/DSC per the material monographs);
- General physicochemical properties of aqueous extracts;
- Biological reactivity: with the 2025 revision, in vitro testing per USP <87> is no longer required for oral and topical dosage forms, while it remains for higher-risk routes (parenteral, inhalation, ophthalmic); a material failing <87> must be investigated further per <88>;
- Composition: extractable elemental impurities and plastic additives, to be characterized and quantified.
A point that is often misunderstood: passing <661.1> is not a formal prerequisite for <661.2>, but a well-characterized material (HDPE and PP resins compliant with <661.1> are considered as such) drastically reduces the risk of surprises during system qualification.
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What USP <661.2> requires of the packaging system
<661.2> applies to the complete system: container, closure, dropper, snap cap and every other component, including hard-to-test systems such as sealed blister cards. Qualification covers three fronts: physicochemical testing of the system, biological reactivity according to the route of administration, and a risk-based Chemical Safety Assessment that considers the system, its materials, its components and the drug product together. Where the risk assessment indicates that experimental data are needed, extractables and leachables studies follow the informational chapters <1663> and <1664>.
This is where the revision really raises the bar: a generic certificate of conformity from the converter is no longer enough. The MA holder or manufacturer must be able to show a documented rationale linking the product's risk (route of administration, physical state, propensity for interaction) to the depth of the data gathered on the system.
<661.1> vs <661.2>: who does what
| Aspect | USP <661.1> | USP <661.2> |
|---|---|---|
| Subject | Material of construction (resin) | Finished packaging system |
| Goal | Material well characterized and suitable for construction | System suited to its intended use with the product |
| Key tests | Identity, physicochemical, biological reactivity (where applicable), elemental impurities and additives | Physicochemical, biological reactivity, risk-based Chemical Safety Assessment (E&L per <1663>/<1664> where needed) |
| Typical user | Resin/component manufacturer, with data shareable downstream | Product owner / packaging site |
| Biological reactivity for oral and topical | Not required (2025 revision) | Not required (2025 revision) |
No grandfathering: the typical audit findings
The transition grants no acquired rights: materials qualified only against the legacy <661> must be requalified against <661.1> and <661.2>. For multi-market products the work must also be coordinated with the European requirements for plastic materials and containers in Ph. Eur. (sections 3.1 and 3.2): the two pharmacopeias are not harmonized here, and a system compliant with Ph. Eur. alone is not automatically defensible as compliant with the <661> suite, nor vice versa. Dossiers and specifications should state explicitly which standard covers which market.
These are the findings that come up most often in audits and inspections:
- SOPs and specifications still citing the legacy <661> tests as the current requirement after February 1, 2026;
- Confusing material level with system level: a dossier full of <661.1> certificates from the resin supplier, but with no <661.2> assessment of the finished system;
- A Chemical Safety Assessment that is missing or photocopied, identical for an eye drop and an oral syrup, with no rationale tied to the route of administration;
- <87> testing performed «out of habit» on oral and topical products, spending on tests no longer required while composition data are missing;
- No oversight of supplier change control: a change of additive in the resin can invalidate the <661.1> characterization the whole structure rests on.
GuideGxP recommendation
Treat the <661> suite as a single flow: inventory the plastic systems in use, map for each one which <661.1> data come from the supplier and which <661.2> assessments are yours, and close the gaps starting from the highest-risk products (parenterals and inhalers). Formalize the Chemical Safety Assessment as a living document, linked to supplier change control, and align component acceptance specifications with the new architecture. For parenteral contact systems, the natural next step is full qualification of the container closure system: our operational guide Extractables & Leachables and USP <381>/<382> for parenterals covers exactly that journey, from the component to the leachable in the patient, with a ready-to-use toolkit.
