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Preparing for USP <665> and USP <1665>
Plastic components and systems have transformed pharmaceutical and biopharmaceutical manufacturing. Flexible, convenient, and operationally efficient, plastic components such as tubing, filters, bioprocessing bags, and connectors are now standard across production environments worldwide, alongside the more historical stainless steel manufacturing plants.
However, this widespread adoption has brought increased regulatory focus. These polymer-based materials are not fully chemically inert.
Plastic materials are formulated with additives such as antioxidants, stabilizers, lubricants, plasticizers, and processing aids. Under certain conditions, these can migrate, as process equipment related leachables (PERLs). Even at trace levels, PERLs can interact with drug substances, biologics, excipients, or formulations, and potentially affect product stability, purity, efficacy, or even patient safety.
The stakes are high. And from May 1, 2026, the regulatory expectations to understand and control these process equipment related leachables become mandatory.
What USP <665> and USP <1665> Require
The United States Pharmacopeia has introduced General Chapter <665>, Plastic Components and Systems Used to Manufacture Pharmaceutical Drug Products and Biopharmaceutical Drug Substances and Products, alongside the companion guideline <1665>. Both chapters were approved in 2024 and become enforceable on May 1, 2026. USP <665> applies specifically to polymeric components and systems used during drug substance and drug product manufacturing and does not apply to final container closure systems, which remain covered under USP <1663> and USP <1664>.
Together USP <665> and USP <1665> establish a structured, risk-based framework for evaluating polymeric components used in pharmaceutical manufacturing. The core requirement is clear: manufacturers must demonstrate that plastic materials used in production do not introduce unacceptable levels of process equipment-related leachables (PERLs), typically through extractables characterisation supported by documented risk assessment, with targeted leachables studies only where scientifically justified.
USP <1665> outlines a two-step approach. First, an initial assessment determines whether components contact the process stream, and whether existing supplier data or prior studies are sufficient to demonstrate material equivalency. If existing data are not sufficient, a formal risk assessment considering factors such as contact duration, temperature, the chemical nature of the process fluid, and material composition should be undertaken.
Based on the outcome, components are categorised as low, moderate, or high risk, and that categorisation determines the scope of extractables testing needed. Targeted leachables or process‑simulation studies are only expected where justified by extractables findings and process risk.
Industry frameworks such as the BioPhorum Operations Group (BPOG) protocols are widely used and represent best practice in the biopharmaceutical sector. However, they are not formal regulatory standards. Manufacturers need to ensure that existing data generated under those protocols aligns specifically with USP <665> and USP <1665> expectations.
For many organisations, that alignment review is where unexpected gaps are identified.
Why Timing Matters More Than You Think
Comprehensive risk assessments and extractables testing programmes take time, particularly for complex bioprocessing and single use systems. Many programmes run for several months before a full data package is ready.
Organisations that begin the process now are in a fundamentally different position to those that wait. Early action means the ability to secure laboratory capacity, identify and close data gaps before they become regulatory problems, and ensure supplier and material qualification is complete ahead of the deadline.
Waiting carries tangible risk: regulatory delays, manufacturing disruptions, supply chain challenges, and, ultimately, threats to product quality and patient safety.
How Resolian Can Help
Resolian’s Extractables and Leachables team provides scientific and analytical support for pharmaceutical and biopharmaceutical manufacturers preparing for USP <665> and USP <1665> compliance. Our role is to generate the technical evidence and data packages that support risk based compliance decisions, aligned with regulatory expectations.
Our Services Include:
Extractables Testing
Comprehensive chemical characterisation of plastic components using multiple extraction solvents and worst-case conditions, in line with USP <1665> principles. Analytical techniques include headspace GC-MS for volatile compounds, GC-MS for semi-volatiles, LC-MS for non-volatile and polar extractables, and ICP-MS for elemental impurities.
Targeted Leachables or Process Simulation Studies (Where Indicated)
Where extractables data, process conditions, or regulatory context indicate the need for further confirmation, Resolian supports targeted leachables or process simulation studies to evaluate relevant process equipment related leachables (PERLs). The scope of such studies is defined case by case, based on documented scientific and regulatory risk considerations.
Toxicological Risk Assessments
Through approved specialist partners, toxicological evaluation of extractables and leachables data to support safety assessment and regulatory justification.
Regulatory Submission Support
Study design and data presentation aligned with USP <665> and USP <1665>, with technical documentation suitable for inclusion in regulatory submissions, as well as packages to support supplier qualification.
The Guide You Need Before the Deadline
The May 2026 deadline is not a distant consideration. For manufacturers with complex single-use systems, the time to act is now.
Resolian brings deep expertise in extractables and leachables science, a GMP-compliant laboratory environment, and a practical understanding of what regulators expect. We help you build the evidence, close the gaps, and move forward with confidence.
