Extractables
Table of Contents
Introduction
Extractables are chemical compounds that can be released from a material, such as pharmaceutical packaging or medical device components, under controlled laboratory conditions. These compounds are typically identified through rigorous testing to ensure the safety and compliance of drug products in the pharmaceutical, biotech, and medical device industries.
Definitions and Concepts
- Extractables: Chemical entities that can be extracted from a material when exposed to specific solvents under exaggerated conditions.
- Leachables: Chemical substances that migrate from packaging or delivery systems into pharmaceutical products under normal storage and use conditions.
- Extraction Studies: Laboratory assessments identifying potential extractables using aggressive solvents and exaggerated exposure conditions.
Importance
Ensuring the safety of pharmaceutical and biotech products requires understanding extractables and their potential to transform into leachables. Regulatory agencies, such as the FDA and EMA, mandate rigorous testing to prevent contamination, toxicity, or adverse interactions with drug formulations. Extractables studies help ensure:
- Compliance with regulatory guidelines (e.g., USP <1663>, ISO 10993).
- Risk assessment for patient safety and product stability.
- Selection of compatible materials for drug containment and delivery.
Principles or Methods
Extractables studies follow structured methodologies to identify potential contaminants in pharmaceutical packaging and medical device materials. Key principles include:
- Solvent Extraction: Using different solvents (e.g., polar, non-polar, acidic, basic) to maximize extraction potential.
- Accelerated Conditions: Applying elevated temperature, pressure, or extended exposure time to simulate worst-case scenarios.
- Analytical Techniques: Employing advanced methods such as Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) for compound identification.
- Risk-Based Assessment: Evaluating detected extractables to determine the likelihood of them becoming leachables and assessing potential toxicity.
Application
Extractables testing is crucial across pharmaceutical, biotech, and medical device industries, including:
- Pharmaceutical Packaging: Assessing plastic vials, rubber stoppers, blister packs, and IV bags to prevent contamination risks.
- Medical Devices: Ensuring biocompatibility of catheters, syringes, and implantable materials.
- Bioprocessing Equipment: Evaluating tubing, filters, and storage containers to mitigate extractable-induced drug degradation.
- Inhalation & Parenteral Drug Delivery: Examining packaging of inhalers, injectables, and transdermal patches for potential leachable compounds.
References
- United States Pharmacopeia (USP) <1663> “Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems”
- ISO 10993-18: “Biological evaluation of medical devices – Chemical characterization of materials”
- PDA Technical Report No. 65: “Risk-Based Approach for Extractables and Leachables Testing”
- FDA Guidance on Container Closure Systems for Packaging Human Drugs and Biologics