Extractables & Leachables
Extractables and Leachables Testing is an analysis of potentially harmful materials that could be administered to a patient with a drug or device. Toxicological assessments may then be made, to quantify a patient’s exposure to each chemical and gauge the level of risk posed by these materials.
Extractables are chemicals generated under exaggerated temperature and time conditions in the presence of an appropriate solvent. Extractables are defined as organic and inorganic contaminants such as plasticizers, antioxidants, surfactants, slip agents, plasticizers, acid scavengers, crosslinking agents, lubricants, residual monomers and oligomers, dyes, elemental impurities etc. that can be extracted from the surfaces of packaging components under extreme conditions such as elevated temperature and pressure or with exposure to solvents.
Leachables are chemicals that migrate spontaneously from a container – closure system, packaging components, and/or processing equipment under recommended or routine conditions of use and storage. Leachables are often a subset of extractables.
Extractables and leachables in medical devices can affect patient safety by causing toxicity, carcinogenicity, or (through interactions with the protein) immunogenicity if administered to patients.
Materials leached from a container or other contact surface during manufacturing into a product may cause chemical affects such as oxidation or aggregation. They may affect the look of the formulation: its color, for example. Leachables could affect product stability over time, lead to immunogenicity caused by altering the product, or change its potency. Leachables may also affect medical diagnostic tests and assay results for a drug substance or product.
Control of extractables and leachables is also required by regulations (ISO 10993-18).
Extractable and leachable studies identify key components using a range of analytical technologies:
- Volatile organic compounds — typically performed using headspace GC-MS
- Semi-volatile organic compounds — typically performed using GC-MS
- Non-volatile organic compounds — typically performed using LC-MS or High Resolution Accurate Mass (HRAM) LC-MS
- Elemental impurities (metals) — typically performed ICP-MS
Extractables and Leachables Testing is an analysis of potentially harmful materials that could be administered to a patient with a drug or device. Toxicological assessments may then be made, to quantify a patient’s exposure to each chemical and gauge the level of risk posed by these materials.
Extractables are chemicals generated under exaggerated temperature and time conditions in the presence of an appropriate solvent. Extractables are defined as organic and inorganic contaminants such as plasticizers, antioxidants, surfactants, slip agents, plasticizers, acid scavengers, crosslinking agents, lubricants, residual monomers and oligomers, dyes, elemental impurities etc. that can be extracted from the surfaces of packaging components under extreme conditions such as elevated temperature and pressure or with exposure to solvents.
Leachables are chemicals that migrate spontaneously from a container – closure system, packaging components, and/or processing equipment under recommended or routine conditions of use and storage. Leachables are often a subset of extractables.
Extractables and leachables in medical devices can affect patient safety by causing toxicity, carcinogenicity, or (through interactions with the protein) immunogenicity if administered to patients.
Materials leached from a container or other contact surface during manufacturing into a product may cause chemical affects such as oxidation or aggregation. They may affect the look of the formulation: its color, for example. Leachables could affect product stability over time, lead to immunogenicity caused by altering the product, or change its potency. Leachables may also affect medical diagnostic tests and assay results for a drug substance or product.
Control of extractables and leachables is also required by regulations (ISO 10993-18).
Extractable and leachable studies identify key components using a range of analytical technologies:
- Volatile organic compounds — typically performed using headspace GC-MS
- Semi-volatile organic compounds — typically performed using GC-MS
- Non-volatile organic compounds — typically performed using LC-MS or High Resolution Accurate Mass (HRAM) LC-MS
- Elemental impurities (metals) — typically performed ICP-MS
| EXTRACTABLES | EXAMPLE METHODS | QUALITATIVE | QUANTITATIVE |
|---|---|---|---|
| Volatile Organic Compound | Headspace GC-MS Headspace GC-FID Headspace GC-FID-MS | X | X |
| Total Organic Carbon (only for aqueous extracting solvents) | — | X | |
| Semi-Volatile Organic Compound | GC-MS GC-FID GC-FID-MS | X | X |
| UPLC/HPLC-MS UPLC/HPLC-UV UPLC/HPLC-UV-MS | not applicable | not applicable | |
| Total Organic Carbon (only for aqueous extracting solvents) | — | X | |
| Non-Volatile Organic Compound | UPLC/HPLC-MS UPLC/HPLC-UV UPLC/HPLC-UV-MS | X | X |
| Total Organic Carbon (only for aqueous extracting solvents) | — | X | |
| Elemental | ICP-MS ICP-AES | X | X |
Quantification of these compounds is performed using relative reference standards, in which a qualified toxicologist calculates the Analytical Evaluation Threshold (AET) or Total Element Exposure (TEE), above which an extractable or leachable needs to be reported for toxicological assessment. Analytical data for these impurity classes is meant to provide information to help customers determine what further studies are needed to mitigate risks associated with the final product.
