Plastic Components and Systems Used to Manufacture Pharmaceutical Drug Products
USP General Chapter <665> establishes a risk-based framework for evaluating plastic components and systems — including single-use systems — used in the manufacture of pharmaceutical drug substances and drug products. It addresses the chemical characterisation of these materials, focusing on extractables and, where warranted by risk, leachables that could migrate into the process stream. The companion chapter <1665> provides the informational guidance supporting <665>.
What this does not cover
stated in the document's own scope- Addresses process-contact manufacturing materials, not the finished container closure system (see <661>/<661.1>/<661.2>)
- Does not cover biological reactivity/biocompatibility — see the <87>/<88> series
- Does not set patient-exposure toxicological limits directly; those follow from risk assessment
- Does not prescribe a single vendor test protocol
Always verify against the current published text before relying on it for a submission or inspection.
Overview
USP General Chapter <665> establishes a risk-based approach for evaluating plastic components and systems, including single-use systems, used to manufacture pharmaceutical drug substances and drug products. It focuses on the chemical characterisation of process-contact plastics — principally extractables studies and, where risk warrants, leachables — and it frames the assessment around process conditions such as contact duration, temperature, solvent characteristics, and surface-area-to-volume ratio. The companion informational chapter <1665> provides the supporting scientific rationale, study-design guidance, and analytical considerations that underpin the <665> requirements.
Legal basis & how it acquires force
USP <665> is a below-1000 general chapter and is therefore intended to be enforceable where invoked; USP-NF chapters gain force in the US through incorporation by reference under the FD&C Act. It supports the underlying GMP expectation that manufacturing materials do not adversely affect product quality. Its official date has been the subject of postponement, so the applicable effective date should be confirmed in the current USP-NF.
Document structure
| Part | Covers |
|---|---|
| Introduction and scope | Plastic components and systems used in manufacture; single-use systems |
| Risk assessment | Risk factors from process conditions determining the level of evaluation |
| Extractables | Study design and analytical characterisation of extractables |
| Leachables | When and how leachables assessment is triggered |
| Companion chapter <1665> | Informational rationale, methods, and worked considerations |
Key requirements
- Apply a risk-based assessment to determine the level of chemical evaluation required
- Perform extractables characterisation of plastic components and single-use systems per the defined protocol
- Escalate to leachables assessment where risk factors warrant it
- Consider process conditions (contact time, temperature, solvent, surface area) in the risk assessment
- Document material identity and component qualification
- Use analytical procedures capable of detecting relevant organic and inorganic extractables
Implementation tips
- Read <665> with the informational <1665> for the underlying risk and analytical rationale
- Leverage supplier extractables data, but confirm it maps to your actual process conditions
- Confirm the current official date in USP-NF before citing effectivity — <665> was postponed
- Scope the assessment to process-contact materials; align it with your existing E&L program
International alignment
USP <665>/<1665> align with the broader extractables and leachables body of practice, including BPOG/BPSA single-use system extractables approaches and ISO 10993-style chemical characterisation principles, providing a compendial framework for process-contact plastics.
USP <665>: frequently asked questions
Quick answers to common questions about USP <665>.
What does <665> apply to?
Plastic components and systems, including single-use systems, used to manufacture drug substances and drug products.
What is <1665>?
The informational companion chapter that provides the scientific rationale and study-design guidance behind <665>.
Is <665> in force now?
Its official date was postponed to 1 May 2026.