Extractables and Leachables in Single-Use Systems: A Procurement Buying Guide

When a lab or manufacturing site sources a single-use system (SUS) — bags, tubing assemblies, filter capsules, connectors, sensors — the plastic itself is not inert. Every polymer, gasket, adhesive, and printed label in that fluid path is a potential source of chemical compounds that can migrate into whatever passes through it. Extractables and leachables (E&L) testing is how a buyer, together with the manufacturer, establishes whether that migration is a real risk to product quality or patient safety, and it is one of the most consequential — and most commonly under-scoped — documentation requirements in single-use system procurement. This guide covers what E&L testing actually evaluates, which standards govern it, and what a procurement officer, lab manager, or QA-adjacent buyer should request from a supplier before committing to a single-use platform.

Extractables vs. leachables: the operational difference

The two terms are related but not interchangeable, and mixing them up is the single most common source of confusion in supplier conversations:

• Extractables are compounds that can migrate out of a plastic component under deliberately aggressive, worst-case laboratory conditions — exaggerated temperature, extended contact time, and solvents chosen to maximize recovery (e.g., water, ethanol/water blends, and a strong acid or base). Extractables studies are generic to the material and are typically generated once by the component manufacturer and shared with customers as a data package, not repeated by every purchaser.
• Leachables are the subset of those compounds that actually migrate into the real product or process fluid, under the actual conditions of use (real contact time, real temperature, real fluid composition, real hold duration). A leachables study is process- and product-specific — it cannot be fully outsourced to the component manufacturer, because the manufacturer does not control what fluid the end user runs through the assembly.

In practice: the manufacturer’s extractables data tells a buyer what could theoretically leach; the buyer’s (or their contract manufacturer’s) leachables study, informed by that extractables data, confirms what actually does leach into their specific product. A supplier who can only offer one half of that picture has not given a buyer everything needed to make a risk-based sourcing decision.

Why this matters for single-use system procurement specifically

Single-use systems have displaced stainless-steel, clean-in-place equipment across much of biopharmaceutical and cell/gene therapy manufacturing precisely because they remove cleaning validation and cross-contamination risk between batches — but they introduce a different risk in its place: a much larger surface area of polymer in direct, often extended, contact with the drug product, buffer, or media. A procurement decision about an SUS component is therefore also a product-quality decision, not just a sourcing or cost decision. Consequences of skipping or under-scoping E&L evaluation on a component include:

• A leachable compound interacting with a biologic (protein oxidation, aggregation) or inhibiting cell growth in a bioreactor bag, discovered only after a batch is already committed.
• A regulatory filing (BLA/NDA/IND) held up or queried because the extractables/leachables data package supporting a single-use component is incomplete or absent.
• An unplanned, costly re-qualification cycle when a supplier changes a resin, additive, or gamma-irradiation source without notifying the buyer — a change that can shift the extractables profile even though the part number stays the same.

These are the reasons E&L documentation belongs in a procurement or vendor-qualification checklist alongside price, lead time, and capacity — not filed away as “a QA problem” to be solved after the purchase order is signed.

The standards and regulatory landscape

No single global regulation prescribes one E&L test method for single-use systems, which is exactly why buyer-side documentation requests matter: the standards below define good practice and a common vocabulary, but a supplier’s actual test data is what a buyer has to evaluate directly.

• USP General Chapters <665> and <1665> — the U.S. Pharmacopeia’s chapters specific to plastic components and systems used in pharmaceutical and biopharmaceutical manufacturing (as distinct from <661.1>/<661.2>, which cover plastic packaging systems for the finished drug product, and <87>/<88>, which cover biological reactivity/biocompatibility rather than chemical extractables). <665> sets extractables-testing and reporting expectations for manufacturing-system components; <1665> is the informational chapter explaining how to design and interpret those studies. USP has postponed the official compliance date for <665>/<1665> more than once since they were first published — confirm the current official/compliance status directly against USP-NF before citing a specific enforcement date to a vendor or auditor.
• The BioPhorum Operations Group (BPOG) extractables protocol — a standardized testing protocol developed by a biopharmaceutical-industry consortium specifically to bring consistency to single-use-system extractables studies, so that data from different component manufacturers can be compared on a like-for-like basis rather than each supplier using its own ad hoc method. Many single-use system manufacturers now publish extractables data generated to the BPOG protocol; asking whether a supplier’s data package follows it is one of the fastest ways to gauge how comparable and audit-ready that data actually is.
• ISO 10993 — the biocompatibility standard series (cytotoxicity, sensitization, irritation) most directly relevant when the single-use component contacts a cell-based product (cell and gene therapy, cell culture media) rather than a small-molecule stream; it addresses biological response, which is a related but distinct question from chemical identification and quantification.
• ICH Q3D / ICH M7 — the International Council for Harmonisation’s guidelines on elemental impurities and mutagenic-impurity risk assessment, which inform how a buyer’s toxicology/quality team sets safety thresholds once leachable compounds are identified, rather than governing the extraction testing itself.

Division of responsibility: what the manufacturer owes you vs. what you own

A clear-eyed procurement checklist separates what a well-documented supplier should hand over versus what stays the buyer’s (or their CMO’s) own responsibility:

• Supplier-provided (extractables): a controlled extractables study report for the specific material/component (not just a generic resin datasheet), material composition and traceability to a defined resin/additive lot, sterilization method and dose (gamma, e-beam, ETO) since irradiation changes extractables profiles, and change-notification commitment if any of those inputs change.
• Buyer-owned (leachables): a leachables study or risk assessment run under your own actual process conditions — product/media composition, contact time, temperature, hold steps — using the supplier’s extractables data as the target-compound list to look for. This is typically commissioned from an in-house analytical group or a contract testing lab, not the component manufacturer.

A buyer who accepts “we have extractables data” as equivalent to “this is safe for our product” has skipped the step that actually answers the safety question.

What to request from a single-use system supplier before purchase

A practical, real documentation request to send a supplier or distributor as part of vendor qualification or an RFP:

• The full extractables study report for the specific part number and material of construction — not a marketing summary, but the underlying analytical report (methods, solvents, conditions, compound list with quantities).
• Confirmation of whether the study followed the BPOG standardized protocol, and if not, what protocol was used and why.
• Material traceability documentation: resin supplier, additive/master-batch composition, and confirmation of manufacturing-site and process consistency across lots.
• Sterilization/irradiation method and validated dose range, since a change here can invalidate prior extractables data.
• A binding change-notification policy: will the supplier notify you before changing a resin source, additive, film construction, or sterilization method on an existing part number, with enough lead time to re-assess?
• Regulatory support materials — a Type III Drug Master File (DMF) reference letter, USP Class VI / biocompatibility data, and a quality/regulatory contact who can respond to audit or filing questions, not just a sales contact.
• For distributors reselling a manufacturer’s single-use components: confirmation that the distributor can obtain and pass through the manufacturer’s full E&L data package on request, and typical turnaround time to do so — a distributor that cannot get this data quickly from its own supply chain adds risk to your timeline, independent of the component’s technical merits.

Evaluating suppliers and distributors on E&L readiness: a practical checklist

None of the criteria below should be read as ranking any specific commercial supplier or distributor as universally “best” — the right choice depends on your product type, regulatory phase (early clinical vs. commercial), and risk tolerance. Use these as evaluation dimensions, not a scorecard that produces a single winner:

• Data completeness — full analytical reports available on request, not just a one-page extractables summary sheet.
• Protocol alignment — testing performed to a recognized, standardized protocol (BPOG) or USP <665>/<1665> framework, so results are comparable across suppliers.
• Change-control transparency — a documented, proactive notification process for material or process changes, not a reactive “we’ll tell you if you ask.”
• Regulatory filing support — willingness and history of providing DMF letters of authorization and responding to customer audits or regulatory queries.
• Consistency across scale — confirmation that the same E&L profile applies from small-scale (e.g., 50 L bag) to the commercial-scale component you’ll actually run, since some E&L data is only generated at one scale.

Where E&L fits in incoming qualification and change control

For a buyer, E&L documentation should be captured at three points in the procurement lifecycle, not treated as a one-time gate at initial vendor approval: (1) at initial component qualification, when the extractables data package is reviewed against your product’s risk profile and any gaps are flagged before the first purchase order; (2) at receipt of each lot, where certificate-of-conformance and traceability documentation confirm the lot matches the qualified material, not a substitution; and (3) whenever the supplier issues a change notification, which should trigger a documented re-assessment of whether the existing extractables data still applies. Building these checkpoints into your incoming-inspection and vendor-management procedures — rather than relying on memory that “we checked this once” — is what actually keeps single-use system procurement compliant as suppliers, resins, and irradiation sources shift over time.

Frequently asked questions

Is extractables and leachables testing required by the FDA for single-use systems?

There is no single FDA regulation that names “E&L testing” as a discrete, universally mandatory step for every single-use component in every context. Instead, the expectation flows from general current Good Manufacturing Practice (cGMP) requirements that manufacturing-contact materials not adulterate the product, reinforced by USP General Chapters <665>/<1665> and reviewer expectations during BLA/NDA/IND filings. In practice, for any product-contact single-use component used in GMP manufacturing, reviewers expect to see extractables data and a leachables risk assessment as part of the filing or audit record.

Do I need my own leachables study if the supplier already gives me extractables data?

Generally yes, for GMP-relevant applications. Extractables data identifies what could migrate under worst-case conditions; it does not confirm what actually migrates into your specific product under your specific process. A leachables study (or a documented, justified risk assessment using the extractables data as a target list) under your real conditions is the step that closes that gap.

What is the difference between USP <665> and USP <661.1>/<661.2>?

<661.1>/<661.2> govern plastic materials and packaging systems for the finished, packaged drug product (e.g., a bottle or blister). <665>/<1665> govern plastic components and systems used during manufacturing — bags, tubing, filters, and other single-use process equipment. They address related but distinct stages of a product’s contact history with plastic.

Does a change in gamma-irradiation dose affect existing extractables data?

It can. Irradiation is one of the process variables most likely to alter a polymer’s extractables profile, because it can break down polymer chains and additives into new migratable species. A dose change, or a switch between gamma and e-beam sterilization, is a legitimate trigger for re-assessing whether prior extractables data still applies — this is exactly the kind of change a supplier’s change-notification policy should proactively flag.

Related CASRAI resources

• Single-Use Assemblies (SUAs) — the dictionary definition of the component category this guide’s documentation requirements apply to.
• cGMP Facility Requirements: Design, Zoning, and Qualification — the facility-level compliance context single-use systems typically operate within.
• Cold Chain Shipping: A Procurement Guide to Evaluating Carriers, Packaging, and Compliance — a parallel example of evaluating suppliers on documented capability rather than marketing claims.