Extractables are compounds that migrate from the contact surface under more aggressive conditions, such as elevated temperature, extended contact time, or aggressive solvent system. Any component that is added to or pulled from the device or the materials used to make the device, including degradants and residuals.
Leachables are compounds that migrate from the contact surface under normal conditions of exposure. Released materials may include plastic components, elastomers, coatings, accelerants, and anti-oxidants. Degradation products from gamma and e-beam sterilization and residual solvents may also be present.
Extractable and Leachable Study Design
Extractables and leachables studies are designed to be optimized and customized for the pharmaceutical container or closure under investigation, such as materials and their compatibility with extraction solvents, type of container, type of contact between the container and the medicinal product, storage conditions, specific administration or reconstitution procedures, type of medicinal product, route of administration, dosing regimen, and associated threshold requirements.
Exhaustive extractions using solvents with a range of polarity (polar, non-polar, mid-range) may be conducted to identify extractable materials These extractable materials will be referenced against known target compounds from material and container preparation and processing. Leachable materials may be extracted using model solvent system comparable to end use applications.
- Organic analysis by GC, GC/MS, HPLC, LC/MS, LC/MS/MS
- Elemental analysis by ICP, GFAA and cold vapor AA
- FTIR and UV/Vis Spectroscopy
- pH and Total Organic Carbon (TOC) provide non-specific indications of chemical migration
- Ion chromatography
- Particle sizing analysis
- Karl Fischer
Extractables Leachables Capabilities
- OINDPs (pMDI, DPI, Nasal Sprays…)
- Dermal and Topical Applications
- Biodisposables / Single Use Systems
- Medical Devices
- Label/Ink Migration
- Drug Delivery Systems
- Primary/Secondary Container Closure Systems
- Raw Material/Polymers
- Material Characterization
- Material Comparison
- Residual Analysis
Toxikon’s Expertise in Extractables & Leachables Testing
Toxikon has developed extensive methodologies for designing studies to identify extractables and leachables in medical products. The demand for these types of studies is increasing, as data from these assessments identifies potential contaminants that migrate from containers, closure systems, tubing, and other materials, potentially rendering medical products unsafe. These materials include, but are not limited to, polymers and other plastics, elastomers, coatings, accelerants, and antioxidants. Degradation products from gamma to e-beam sterilization processes to residual solvents from manufacturing may also be present.
Toxikon uses a combination of commercially-available reference databases as well as our proprietary database, called TOXASSURE, to assist in the conduct of extractable and leachable assessments.