Extractables and Leachables Testing Services: Safeguarding Product Integrity and Patient Safety
As regulations tighten and consumer awareness grows, Extractables and Leachables (E&L) testing has emerged as a critical quality assurance step in the development and commercialization of pharmaceutical products, medical devices, biologics, and food packaging. These testing services play a pivotal role in evaluating potential chemical contaminants that may migrate from container-closure systems, delivery devices, or packaging materials into the final product.
What are Extractables and Leachables?
Extractables are compounds that can be extracted from materials under aggressive laboratory conditions (e.g., high temperature, solvents). They represent a worst-case scenario and help identify potential leachables early in the development cycle.
Leachables, on the other hand, are compounds that actually migrate into the drug product or patient-contacting fluid during normal storage or usage conditions.
Understanding both is crucial for ensuring product stability, efficacy, and, most importantly, patient safety.
Why E&L Testing is Essential
Regulatory ComplianceAgencies like the U.S. FDA, EMA, and China’s NMPA mandate E&L testing as part of product submissions. Guidelines from USP <1663> and <1664>, as well as ISO 10993 for medical devices, provide detailed frameworks for assessing risks.
Patient SafetyLeachable substances—such as plasticizers, antioxidants, or residual solvents—can pose toxicity risks. Thorough testing mitigates potential adverse effects.
Product IntegrityChemical leaching can impact drug potency, formulation stability, and shelf life, making E&L testing crucial for maintaining product quality.
Risk AssessmentProactive E&L studies help manufacturers understand and minimize risks associated with material compatibility and migration over time.
The E&L Testing Process
E&L testing typically follows a tiered approach:
Material CharacterizationIdentify and quantify extractables from packaging or device components using simulated conditions.
Simulated Use TestingStudy the leachables under real-time or accelerated storage conditions with the actual product formulation.
Toxicological Risk AssessmentEvaluate potential health impacts of detected leachables using safety thresholds like the Threshold of Toxicological Concern (TTC).
Reporting and Regulatory FilingComprehensive documentation supports product registration and regulatory audits.
Advanced Analytical Techniques
Modern E&L testing leverages state-of-the-art instrumentation, including:
Gas Chromatography-Mass Spectrometry (GC-MS)
Liquid Chromatography-Mass Spectrometry (LC-MS)
Inductively Coupled Plasma Mass Spectrometry (ICP-MS)
Fourier-Transform Infrared Spectroscopy (FTIR)
Headspace Analysis for volatile compounds