Ensuring the safety and efficacy of pharmaceutical products and medical devices is a cornerstone of responsible product development. Among the many rigorous quality control measures that manufacturers must adopt, extractables and leachables (E&L) testing stands out as one of the most vital. These tests help identify potentially harmful chemical compounds that could migrate from packaging, container closure systems, or device materials into a drug or biologic product.
While “extractables” and “leachables” are often mentioned together, they are not interchangeable terms. Understanding their distinct roles, methodologies, and regulatory implications is crucial—especially when patient safety and compliance with global regulatory standards are at stake.
What Are Extractables and Leachables?
At a high level, the difference comes down to potential versus actual exposure.
- Extractables are chemical substances that can be released from materials under exaggerated or aggressive laboratory conditions, such as elevated temperatures or exposure to strong solvents. These test conditions are designed to simulate a worst-case scenario, generating a comprehensive chemical profile of materials that might come into contact with a drug product.
- Leachables, by contrast, are compounds that actually migrate from container closure systems or device components into the product under real-world storage and use conditions. These are the compounds to which a patient might ultimately be exposed.
In essence, extractables testing is predictive and theoretical; leachables testing is confirmatory and practical. To learn more, refer to our article: What is E&L testing?
Key Differences Between Extractables and Leachables Testing
| Aspect | Extractables Testing | Leachables Testing |
| Objective | Identify all potential leachable compounds | Confirm which compounds actually migrate into the product |
| Conditions | Accelerated or exaggerated (e.g., heat, solvents) | Realistic, based on intended storage and usage |
| Timing | Early in product development | During stability studies or shelf-life evaluation |
| Analytical Scope | Broad chemical screening | Targeted analysis based on prior extractables study |
| Regulatory Emphasis | Material characterization and risk assessment | Clinical relevance and patient safety |
Analytical Techniques Used in E&L Testing
Both extractables and leachables testing rely on advanced analytical chemistry techniques. Some of the most commonly used techniques include:
- Gas Chromatography-Mass Spectrometry (GC-MS) – Ideal for identifying volatile and semi-volatile organic compounds.
- Liquid Chromatography-Mass Spectrometry (LC-MS) – Used for non-volatile, polar, and thermally labile compounds.
- Inductively Coupled Plasma Mass Spectrometry (ICP-MS) – Designed for the detection and quantification of elemental impurities and trace metals.
These methods not only help identify extractables during material screening, but they also serve as the backbone for quantitative leachables testing, especially when developing and validating product-specific analytical methods.
Regulatory Landscape and Standards
Regulatory agencies, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), place a high priority on E&L evaluations to ensure that pharmaceuticals and medical devices are safe throughout their lifecycle.
Relevant standards and guidance documents include:
- USP <1663> – Guidelines for the assessment of extractables from packaging and delivery systems.
- USP <1664> – A companion document that focuses on leachables testing protocols.
- ISO 10993-18 – International guidance for the chemical characterization of medical device materials as part of biocompatibility assessments.
Staying aligned with these guidelines not only ensures regulatory compliance but also helps de-risk product development and accelerate time-to-market.
Why Both Tests Are Critical in Product Development
E&L testing is more than just a regulatory requirement—it’s an essential component of product safety and design validation.
- Extractables studies provide early warning signals that allow manufacturers to make informed decisions about material selection, formulation compatibility, and packaging design.
- Leachables studies offer real-world evidence to confirm that products remain free of harmful contaminants over their intended use.
This dual approach supports a science-based risk assessment framework, which is increasingly preferred by regulators and helps companies build robust data packages to support new drug applications (NDAs), biologics license applications (BLAs), or device approvals.
Partnering with Experts in E&L Testing
Because of the technical complexity, regulatory scrutiny, and high stakes involved, many manufacturers turn to specialized laboratories for their E&L studies. At Jordi Labs, our team of polymer scientists, analytical chemists, and toxicologists collaborates to design and execute custom extractables and leachables programs tailored to your product.
With capabilities that include advanced chromatography, mass spectrometry, and method development, we help you:
- Characterize materials across a wide range of polymers and elastomers
- Identify and quantify trace-level contaminants
- Develop targeted leachables assays aligned with extractables results
- Generate robust, audit-ready documentation for regulatory submissions
Making Data-Driven Decisions for Safer Products
The interplay between extractables and leachables testing is foundational to modern pharmaceutical and medical device development. While extractables testing illuminates what could happen under stressed conditions, leachables testing answers what does happen under actual conditions of use.
Together, they form a comprehensive quality control strategy that protects patients and ensures compliance. With Jordi Labs as your testing partner, you gain not just data, but insights—supporting confident, science-driven decisions at every stage of development.
Need guidance on building your E&L strategy? Contact Jordi Labs to learn how our custom testing services can support your product from concept to commercialization.
