Extractable and leachable testing is important with respect to safety and toxicology of medical devices and packaging as Leachables from container closure systems and devices may compromise patient safety.
Capzer Pharmaceuticals has the capability of conducting comprehensive extractable and leachable studies of materials such as container closure systems and devices. The study approaches include identifying extractables, compounds that can be extracted from the study materials under exaggerated conditions, and leachables, compounds that leach from a device in direct or indirect contact with the drug product during normal use.
Extractables and leachables may include both organic and inorganic compounds and may include:
- additives such as lubricants, accelerators, monomers and high molecular weight oligomers from incomplete polymerization
residual solvents - degradation products from temperature, absorption, hydrolysis, oxidation, corrosion or dissolution
- process such as mould release agents and anti-static and anti-stick agents.
The study approach involve the following steps:
Subject the material under study to exaggerated worst-case conditions
Characterize the constituents that are extracted from a component under these exaggerated conditions. Extraction conditions such as solvents, extraction time and temperature are chosen based on guidance such as USP xxx
The extracts are then analyzed and semi-quantitated using the following techniques and instrumentation:
- Ultra Performance Liquid Chromatography-Photo Diode Array-Triple Quadrupole Mass Spectrometry (UPLC-PDA-QQQ-MS) to identify non-volatile organic compounds.
- Direct Injection Gas Chromatography-Mass Spectrometry (DI-GC-MS) to identify semi-volatile organic compounds.
- Static Headspace Gas Chromatography-Mass Spectrometry (HS-GC-MS) to identify volatile organic compounds.
- Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) to identify elemental impurities.
- Non-Volatile Residue (NVR) analysis to establish exhaustive extraction conditions.
Once extractables are evaluated, a list of potential target leachable compound of toxicological concern are identified to develop a specific quantitative analytical method for long term leachable study. Methods developed to quantify leachables can be validated and used in long term stability studies.