The Importance of E&L Testing: Regulatory Perspectives

In the highly regulated pharmaceutical, biopharmaceutical, and medical device industries, ensuring patient safety and product integrity is paramount. Extractables and leachables (E&L) testing has emerged as a critical component of regulatory compliance. These tests identify and quantify potentially harmful chemical substances that may migrate from packaging, manufacturing systems, or delivery devices into the product, potentially impacting patient health or product efficacy. This article explores the significance of E&L testing, its regulatory landscape, methodologies, and its pivotal role in safeguarding public health.

Learn the basics of E&L testing in simple terms – Extractables and Leachables (E&L) Testing

Extractables are chemical compounds that can be extracted from a material under aggressive laboratory conditions, such as exposure to aggressive solvents or high temperatures. They represent the worst-case scenario of chemical migration.

Leachables are compounds that migrate into a drug product or patient-facing system under normal use conditions. These substances often originate from:

• Primary Packaging Materials (e.g., glass vials, plastic containers, rubber stoppers).
• Manufacturing Components (e.g., tubing, filters, and processing equipment).
• Delivery Devices (e.g., inhalers, syringes, and infusion pumps).

The Need for E&L Testing

E&L testing is crucial for several reasons:

• Patient Safety: Leachables can pose toxicological risks, including carcinogenic, mutagenic, and teratogenic effects.

See how E&L testing protects patients – The Role of E&L Testing in Ensuring Patient Safety 

• Regulatory Compliance: Stringent guidelines from the FDA and other regulatory bodies mandate comprehensive E&L evaluations.
• Product Quality Assurance: Prevents drug-product interactions, ensuring stability and efficacy.
• Global Market Access: Complying with U.S. and international regulations facilitates seamless product approval and distribution.

Curious about how much E&L testing costs? Read this – Cost of Extractables and Leachables Testing

Regulatory Perspectives in the United States

Regulatory agencies, including the FDA and USP (United States Pharmacopeia), emphasize rigorous E&L testing to mitigate risks associated with chemical migration. Key guidelines include:

FDA Guidance

1. Container Closure Systems: FDA guidance requires robust assessments of container closure systems to ensure they do not adversely interact with drug products.
2. Quality by Design (QbD): Encourages integrating E&L considerations into product development.

United States Pharmacopeia (USP)

• USP <1663>: Focuses on assessing extractables from pharmaceutical packaging and delivery systems.
• USP <1664>: Addresses the evaluation of leachables and their impact on drug product quality.

ICH Guidelines

• ICH Q3D: Emphasizes the control of elemental impurities in drug products.
• ICH Q8: Highlights the importance of understanding material compatibility in pharmaceutical development.

Other Regulatory Bodies

Organizations such as the International Organization for Standardization (ISO) and ASTM International also provide standards for E&L testing methodologies.

Applications of E&L Testing

E&L testing is integral to:

• Pharmaceutical Packaging: Ensures compatibility and safety of packaging materials.
• Biopharmaceutical Manufacturing: Validates that equipment does not release harmful compounds.
• Medical Devices: Evaluates device safety by identifying potential leachables. See how we test leachables in medical devices – Case Study: Identifying and Mitigating Leachables in Medical Devices 
• Combination Products: Assesses interactions between drug formulations and delivery devices.

Learn how E&L testing applies to respiratory devices – Extractables and Leachables (E&L) Testing for Inhalation and Nasal Drug Products: A Step-by-Step Guide

E&L Testing Methodologies

Effetive Extractables and leachables Testing involves a systematic approach comprising:

Study Design

• Material Selection: Identify components that may release extractables or leachables.
• Simulated Conditions: Mimic worst-case and real-use scenarios.

How Much Does Extractables and Leachables (E&L) Testing Cost in 2025? Click here to make your testing plan cost-efficient.

2. Analytical Techniques

• Gas Chromatography-Mass Spectrometry (GC-MS): Ideal for volatile and semi-volatile compounds.
• Liquid Chromatography-Mass Spectrometry (LC-MS): Suitable for non-volatile and polar compounds.
• Inductively Coupled Plasma Mass Spectrometry (ICP-MS): Detects elemental impurities.
• Fourier Transform Infrared Spectroscopy (FTIR): Identifies organic functional groups.

3. Toxicological Risk Assessment

• Identifies and quantifies risks posed by detected leachables.
• Determines permissible exposure levels (PELs) based on toxicological data.

4. Data Interpretation and Reporting

• Comprehensive documentation of test results.
• Correlation of findings with regulatory requirements.

Challenges in E&L Testing

• Complexity of Materials: Diverse polymeric materials complicate extractable profiling.
• Analytical Sensitivity: Detecting trace levels of leachables requires cutting-edge instrumentation.
• Data Interpretation: Distinguishing between harmful leachables and benign substances demands expert analysis.

Still have questions about E&L testing? Check this –  Top Questions About E&L Testing Answered 

Emerging Trends in E&L Testing

Advanced Analytical Technologies

• High-resolution mass spectrometry and multi-dimensional chromatography enhance detection capabilities.

2. Risk-Based Approaches

• Emphasizing risk assessments over exhaustive testing to optimize resources.

3. Digitalization

• Integration of AI and machine learning for predictive toxicology and material behavior modeling.

4. Sustainability

• Developing eco-friendly packaging materials to reduce extractable risks.

See how we solved a real E&L challenge – Case Study: Enhancing Product Safety Through Comprehensive E&L Testing 

Why Choose ResolveMass Laboratories for E&L Testing?

ResolveMass Laboratories Inc. stands out as a leader in extractables and leachables (E&L) testing in the United States due to:

1. State-of-the-Art Facilities

• Equipped with advanced analytical instruments, including GC-MS, LC-MS, and ICP-MS.

2. Expert Team

• Our team comprises experienced chemists, toxicologists, and regulatory specialists.

3. Comprehensive Services

• From study design to toxicological assessments, we provide end-to-end solutions.

4. Regulatory Expertise

• In-depth understanding of FDA, USP, and ICH guidelines ensures compliance.

5. Tailored Solutions

• Custom testing protocols designed to meet client-specific requirements.
• Need a custom study design? We’ve got you – Customized E&L Testing Solutions for Your Industry

See the full list of E&L testing services offered – Extractables and Leachables services

ResolveMass Laboratories Inc.: Comprehensive Scientific Expertise You Can RelyResolveMass Laboratories Inc. is a trusted Canadian contract research organization offering a wide spectrum of specialized services spanning polymer synthesis, advanced analytical testing, and custom organic synthesis. With over a decade of experience supporting pharmaceutical, biotech, and industrial clients, we bring scientific precision and regulatory insight to every project. Our core capabilities include Polymer Synthesis and Characterization, Peptide Characterization, Organic Synthesis, Nitrosamine Testing and Analysis, PFAS Testing, and Extractable & Leachable Studies, as well as a broad suite of analytical techniques such as HPLC, GC-MS, MALDI-TOF, NMR, and FTIR. 

Our multidisciplinary team includes chemists, analytical scientists, and regulatory experts with advanced academic and industry backgrounds. We excel at developing customized, high-quality solutions—whether you need innovative polymer designs, impurity profiling, or confirmatory testing that meets global regulatory standards. 

Clients across North America choose ResolveMass Laboratories for our deep technical knowledge, commitment to quality, and ability to deliver reproducible, reliable data that drives confident decision-making. When precision, innovation, and trust matter—ResolveMass is your partner of choice. 

Need full-service support? Check this out – Choosing the Right E&L Testing Service Provider 

REFERENCES

1. Thomas F. Understanding Evolving E&L Regulations. In the Lab eNewsletter. 2020 Jan 8;15(1).
2. Vas G, Fleck L, Comstock K, Cole J. Extractable and leachable testing for pharmaceutical packaging, finished pharmaceutical products, and medical devices: an analytical perspective.
3. Ramamoorthy S, Chong NS, Hotha KK. Strengthening Extractable & Leachable Study Submissions: Best Practices to Avoid Regulatory Deficiencies. American Journal of Analytical Chemistry. 2024 Dec 5;15(12):368-94.