Extractables & Leachables Testing — Study Design for Devices & Packaging

Extractables and leachables studies characterize what can migrate from a material, container or device into a product or patient-contact scenario. The study design — solvents, conditions and analytical breadth — determines whether the data can support a toxicological assessment at all.

Design from the contact scenario

Exaggerated extraction is not automatically conservative: overly aggressive conditions can create artefacts never seen in use. Define the contact type, duration, temperature and formulation for devices (ISO 10993-18 frames chemical characterization) or for packaging systems. Agree screening, identification and quantitation thresholds with the laboratory and the toxicologist before analysis, not after a list of unknowns arrives.

Ask how unknowns are identified

A chromatogram full of unidentified peaks has limited value. Ask which techniques and libraries are used, how identifications are confirmed, what reporting threshold applies and how semi-volatile, non-volatile, elemental and volatile fractions are each covered. Confirm the analytical evaluation threshold basis with the assessor who will use the data.

Connect chemistry to the toxicological assessment

The laboratory produces chemical data; a qualified assessor interprets patient or product risk. Agree the data format, uncertainty and identification confidence the assessor needs. Extraction studies, simulation studies and leachables surveillance answer different questions — specify which the programme requires and how changes in material or supplier will be handled.

Extractables, leachables and product context

Extractables describe constituents released under defined laboratory extraction conditions; leachables concern release under actual or justified simulated use. Start with composition, polymers, additives, adhesives, coatings, processing aids and manufacturing/sterilization residues. Device patient exposure differs from drug-container interactions and pharmaceutical stability programmes. Combination products need coordinated device and drug evidence—not an unqualified device protocol applied to every container.

Distinguish final guidance from draft recommendations

FDA's September 2024 chemical-analysis guidance is draft — not for implementation; it is not final guidance or mandatory law. FDA's September 2023 risk-based biological-evaluation guidance remains final. Agree the applicable evidence strategy rather than treating draft chemistry recommendations as a universal test requirement.

What to include in your buyer brief

Start with the decision the work must support. Unknown details can be clarified after the initial inquiry.

Product, materials/formulation, patient or drug contact, contact duration, intended use and target market; identify changed materials, suppliers or processes.
Finished configuration, sample count and lots, sterilization modality/cycles, aging and storage history; justify worst-case variants and destructive allocations.
Existing evaluation plan, drawings, specifications, methods/editions, previous reports and acceptance criteria; send confidential files only through the private intake.
Required report, quality/accreditation scope, budget range, location, shipping constraints and decision deadline; ask the provider to explain exclusions and subcontracted work.

Reference versus candidate medical plastics and colorants

Compare the reference and candidate finished components, documented resin identity when available, pigment/dye or additive changes, manufacturing and cleaning/sterilization histories, and actual exposure. Unknown composition, sample allocation and test panels remain questions to resolve—not inferred facts. Material identification and color comparison do not establish biological safety.

Propose methods around the evidence gap

Ask the provider whether FTIR, DSC or other material identification, targeted chemistry, extraction studies and toxicological interpretation can answer the comparison question. These are possible proposals, not prescribed tests. Biological compatibility, chemical/material resistance and product interactions are different scopes. A qualified evaluator should justify existing evidence, chemical characterization and any targeted biological testing after a material or colorant change.

Plan, evaluate and test: separate the deliverables

A biological evaluation plan (BEP) identifies contact, duration, existing evidence and gaps; a biological evaluation report (BER) integrates the evidence and rationale. An endpoint laboratory report answers a scoped test question, not the entire biological evaluation. A qualified evaluator should justify endpoint selection and use of prior evidence; not every material change requires every test.

Chemistry versus toxicological interpretation

ISO 10993-18 chemical characterization addresses what substances may be present or released and the analytical coverage/limitations. ISO 10993-17 toxicological risk assessment interprets constituent exposure, toxicological evidence and uncertainty in the device-use context. A chemical list alone is not a safety conclusion, and a TRA cannot cure poorly justified extraction or uncharacterized analytical gaps.

Extractables, leachables and residuals

Forced extractables explore potential release under justified exaggerated conditions; actual or simulated-use leachables address release under relevant contact conditions. Neither automatically substitutes for the other. Distinguish manufacturing residuals such as monomers, solvents and processing aids from sterilization residuals such as ethylene oxide and relevant reaction products. Define analytical targets, exposure assumptions, recovery, reporting thresholds and uncertainties with the provider; no universal panel.

Sample considerations

Provide material composition, processing aids, sterilization history and supplier information.
Describe the product contact scenario: formulation, volume, duration, temperature and patient or consumer exposure.
Agree extraction solvents/conditions, thresholds, replicate units and retained samples.

Questions to ask a laboratory

Which analytical techniques cover volatile, semi-volatile, non-volatile and elemental species?
How are unidentified compounds handled and at what threshold?
What data package does your toxicological assessor require?

Laboratories with relevant capabilities

Medical Engineering Technologies (MET) (Dover, Kent) — Extractables & Leachables
Nelson Labs Europe (Leuven, Flemish Brabant) — Extractables & Leachables
NAMSA (Northwood, OH) — Extractables & Leachables
Jordi Labs (Mansfield, MA) — Extractables & Leachables
Cambridge Polymer Group (Woburn, MA) — Extractables & Leachables
Alcami (Wilmington, NC) — Extractables & Leachables

Frequently asked questions

Do I need extractables, leachables, or both?: Extractables studies usually come first to identify what could migrate; leachables studies then confirm what does under actual use conditions.