Introduction
E&L studies for pharmaceutical packaging are essential for ensuring the safety, quality, and regulatory compliance of drug products. These studies investigate potential extractables and leachables—chemical compounds that may migrate from packaging materials into pharmaceutical products. As regulatory expectations tighten and drug delivery systems grow more complex, pharmaceutical companies must adopt a thorough, science-driven strategy for E&L studies for pharmaceutical packaging.
At ResolveMass Laboratories Inc., we have extensive expertise in conducting extractables and leachables analysis. Our validated analytical platforms help pharmaceutical companies meet the highest standards set by agencies such as the FDA, EMA, and Health Canada. In this blog, we break down the step-by-step process of conducting E&L studies for pharmaceutical packaging, including analytical methods, regulatory requirements, and technical insights.
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What Are E&L Studies for Pharmaceutical Packaging?
Understanding Extractables
Extractables are chemical compounds that can be extracted from pharmaceutical packaging or container closure systems under aggressive conditions (e.g., high temperature, strong solvents). These compounds represent the worst-case scenario for chemical migration.
Understanding Leachables
Leachables, in contrast, are compounds that actually migrate into the drug product under normal storage conditions. They pose direct toxicological risks to patients and must be thoroughly identified and quantified.
E&L studies for pharmaceutical packaging encompass both extractables and leachables evaluations, supporting product safety over the entire shelf life.
Step 1: Material Characterization
Before launching into E&L studies, the first step is to gather detailed information about the pharmaceutical packaging system. This includes:
- Polymer composition of plastics
- Elastomer formulations in stoppers
- Coatings, adhesives, and inks
Thorough material characterization ensures targeted testing, reducing unnecessary complexity and improving regulatory defensibility.
Step 2: Design of Extraction Studies
Custom extraction studies are the foundation of E&L studies for pharmaceutical packaging. Extraction conditions are designed based on:
- Dosage form (parenteral, oral, ophthalmic, etc.)
- Storage temperature and duration
- Drug solvent system
Solvents typically include:
- Aqueous solution (pH 2–9)
- Organic solvents (isopropanol, ethanol)
- Mixed solvents (PEG, water/acetonitrile)
Extraction vessels, surface area to volume ratios, and incubation parameters are carefully controlled to simulate packaging interactions.
Step 3: Analytical Techniques for E&L Studies for Pharmaceutical Packaging
LC-MS (Liquid Chromatography–Mass Spectrometry)
Used to detect semi-volatile and polar compounds. LC-MS is especially useful for identifying unknown organic extractables and leachables.
GC-MS (Gas Chromatography–Mass Spectrometry)
Essential for volatile organic compounds (VOCs). GC-MS allows identification of plasticizers, residual solvents, and small molecule impurities.
ICP-MS (Inductively Coupled Plasma Mass Spectrometry)
Used for elemental impurities such as heavy metals. ICP-MS ensures materials meet ICH Q3D limits for elemental leachables.
FTIR and NMR (Supplementary Techniques) E&L Studies for Pharmaceutical Packaging
- FTIR helps with rapid material fingerprinting.
- NMR is used for detailed structural elucidation of unknowns when MS data is inconclusive.
Step 4: Leachable Simulation Studies
Leachables testing involves analyzing drug product formulations that have been stored in the actual packaging for a defined period. This confirms which extractables are truly leachable.
- Real-time or accelerated storage studies
- Periodic sampling and analytical monitoring
- Toxicological risk assessment (Threshold of Toxicological Concern, TTC)
E&L studies for pharmaceutical packaging must be conducted under conditions that mimic the intended use and stability of the product.
Step 5: Data Interpretation and Reporting
The final step involves compiling a comprehensive E&L report:
- Summary of extraction procedures
- Full identification and quantification of compounds
- Analytical method validation
- Justification of safety thresholds
- Comparison with compendial requirements (e.g., USP <1663> and <1664>)
Regulatory agencies expect clear documentation demonstrating that the drug product remains safe throughout its lifecycle.
Learn more about how ResolveMass approaches extractables and leachables testing
Regulatory Considerations for E&L Studies for Pharmaceutical Packaging
E&L studies for pharmaceutical packaging are increasingly regulated:
- USP <1663> covers assessment of extractables in pharmaceutical packaging.
- USP <1664> provides guidance on leachables testing under simulated product conditions.
- ICH Q3D mandates risk-based control of elemental impurities.
- FDA Guidance for container closure systems in drug products emphasizes extractables and leachables control.
ResolveMass ensures all E&L testing is aligned with these global regulatory frameworks.
Why Choose ResolveMass for E&L Studies for Pharmaceutical Packaging?
- ISO 17025-accredited laboratory
- State-of-the-art LC-MS, GC-MS, and ICP-MS platforms
- Experienced team of analytical chemists and toxicologists
- Rapid turnaround and custom testing protocols
With a track record of supporting NDA/ANDA and biologics submissions, ResolveMass is a trusted partner for E&L studies for pharmaceutical packaging.
Conclusion
E&L studies for pharmaceutical packaging are essential for safeguarding patient health, ensuring regulatory compliance, and maintaining product integrity. From understanding the materials to selecting advanced analytical techniques like LC-MS, GC-MS, and ICP-MS, each step must be executed with precision. At ResolveMass Laboratories Inc., we offer end-to-end support for extractables and leachables analysis.
For your next drug development or packaging qualification project, partner with our scientific team to design a robust E&L testing strategy that aligns with global expectations.
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ResolveMass Laboratories Inc.: Comprehensive Scientific Expertise You Can Rely On
ResolveMass 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.
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