Introduction
When a leading pharmaceutical manufacturer identified possible nitrosamine leachables in its infusion bag system, ResolveMass Extractables and Leachables Testing became the trusted partner to detect and manage the risk. Using advanced analytical CRO expertise, ResolveMass Laboratories Inc. created a complete, regulatory-compliant E&L testing program to safeguard product quality and ensure patient safety.
This case study demonstrates how ResolveMass Laboratories’ E&L testing solutions empower pharmaceutical companies with accurate, fast, and cost-efficient methods for detecting and controlling nitrosamines in packaging systems. Through scientific precision, adherence to global standards, and a proactive approach, ResolveMass has built a strong reputation for reliable Extractables and Leachables (E&L) testing services.
🔹 Quick Summary
✅ Objective: Detect and mitigate nitrosamine leachables in infusion bag systems.
✅ Approach: Comprehensive E&L testing compliant with ISO 10993-18 and USP <1663>/<1664> guidelines.
✅ Outcome: Accurate identification and quantification of nitrosamines using advanced techniques.
✅ Impact: Improved regulatory approval process and ensured patient protection.
By combining analytical precision with regulatory knowledge, ResolveMass ensured complete accuracy, speed, and compliance throughout each phase of the study.
Understanding Nitrosamine Leachables in Infusion Bags
Nitrosamines are potentially harmful compounds that may migrate into infusion solutions from packaging materials like rubber, tubing, or polymer-based films. Identifying these trace contaminants requires advanced ResolveMass Extractables and Leachables Testing methods supported by validated analytical procedures.
At ResolveMass Laboratories, expert scientists use sophisticated tools such as:
- Gas Chromatography–Mass Spectrometry (GC-MS)
- Liquid Chromatography–Mass Spectrometry (LC-MS)
- Thermal Desorption Analysis
- Headspace GC for volatile organic compounds
These combined analytical techniques allow comprehensive evaluation of extractables (under extreme conditions) and leachables (under real-use conditions). This ensures each sample is assessed accurately and meets international regulatory expectations.
Learn more about our Analytical Techniques for E&L Testing.
Case Study Objective: Nitrosamine Detection in Infusion Bags
The client required ResolveMass Extractables and Leachables Testing to:
- Identify possible nitrosamine sources from bag films and tubing.
- Measure migration levels under simulated use conditions.
- Demonstrate full compliance with FDA, EMA, and Health Canada guidelines.
ResolveMass’ analytical CRO experts created a customized E&L study based on USP and ISO standards. The testing achieved detection of nitrosamines at parts-per-billion (ppb) levels, ensuring patient safety and regulatory confidence. Each phase of the process was thoroughly documented and validated for reliability.
Study Design and Testing Approach
| Phase | Objective | ResolveMass Expertise Applied |
|---|---|---|
| 1. Controlled Extractables Study | Identify potential nitrosamines using worst-case solvents | Controlled Extractables Study |
| 2. Simulated Use Leachables Study | Quantify nitrosamines under actual storage conditions | Custom E&L Study Design Services |
| 3. Analytical Quantification | Confirm trace-level detection using LC-MS/MS | Analytical Evaluation Threshold |
| 4. Risk Assessment and Reporting | Assess toxicological relevance | Affordable E&L Testing Solutions |
Each stage followed the Extractables and Leachables FDA Guidance, maintaining precision and regulatory alignment. The structured testing approach not only identified current risks but also provided a foundation for ongoing quality control in medical packaging.
Analytical Expertise and Technology
ResolveMass Laboratories operates as a modern analytical CRO equipped with the latest tools for ResolveMass Extractables and Leachables Testing. Key technologies include:
- LC-MS/MS for non-volatile nitrosamines
- GC-MS for volatile compounds (NDMA, NDEA)
- ICP-MS for trace metal leachables
- TOC analysis for total organic content
This advanced setup ensures the complete identification of organic, inorganic, volatile, and non-volatile substances. The combination of these instruments with strong data validation protocols allows for consistent and reproducible results across all test matrices.
Explore our E&L Testing for Medical Devices and Multi-Matrix E&L Testing Services.
Results: Clear Detection and Risk Mitigation
Through rigorous analysis, ResolveMass Extractables and Leachables Testing identified:
- Three nitrosamine compounds below the Analytical Evaluation Threshold (AET).
- No measurable nitrosamine migration under real-use conditions.
- Full toxicological clearance in compliance with USP <1664> standards.
These verified results confirmed the safety of the infusion bag system for both clinical and commercial applications. The validated findings supported the client’s global regulatory submissions and enhanced long-term product confidence.
Learn more about our E&L Testing for Regulatory Submission.
Impact on Regulatory Compliance
ResolveMass Laboratories’ testing services ensured:
- Adherence to ICH M7 nitrosamine guidelines.
- Documentation that aligns with EMA and Health Canada standards.
- Reliable data sets for NDA and ANDA submissions.
For pharmaceutical clients, the Fast E&L Testing Services from ResolveMass provide timely, high-quality results essential for quick regulatory approvals. This efficiency minimizes delays and reinforces compliance confidence worldwide.
Key Takeaways
- ResolveMass Extractables and Leachables Testing efficiently manages nitrosamine risks in infusion systems.
- End-to-end CRO support covers study design, toxicology evaluation, and compliance documentation.
- Pharmaceutical clients achieve faster approvals and stronger patient safety assurance.
- ResolveMass’ proven accuracy and integrity make it a global leader in E&L testing.
Conclusion
This case study highlights ResolveMass Laboratories Inc. as a trusted global partner for Extractables and Leachables (E&L) testing—particularly for nitrosamine risk evaluation in infusion products. The company’s scientific expertise, regulatory knowledge, and advanced technology enable safe, compliant, and high-performing pharmaceutical solutions.
With ResolveMass Extractables and Leachables Testing, manufacturers can confidently protect patient health, maintain compliance, and accelerate their path to market success.
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FAQs on Extractables and Leachables Testing
Extractables are substances that can be released from packaging materials under extreme or accelerated conditions, while leachables are compounds that migrate into the product during actual use. ResolveMass Extractables and Leachables Testing identifies both types using validated analytical methods, ensuring the safety, quality, and stability of infusion bag systems.
Nitrosamines are known to be potentially carcinogenic and must be carefully monitored in medical packaging. Through ResolveMass Extractables and Leachables Testing, these impurities are detected at trace levels to prevent patient exposure, maintain regulatory compliance, and protect the manufacturer’s product integrity.
Nitrosamine testing for extractables and leachables follows strict international guidelines such as ISO 10993-18, USP <1663>/<1664>, and ICH M7. ResolveMass Extractables and Leachables Testing fully aligns with these standards to provide defensible, compliant, and globally accepted analytical data.
Accuracy is achieved through the combination of LC-MS/MS, GC-MS, and other validated analytical instruments. Each study under ResolveMass Extractables and Leachables Testing follows Good Laboratory Practices (GLP) and internal peer review to guarantee reliable, precise, and reproducible results every time.
The Analytical Evaluation Threshold, or AET, defines the minimum level at which leachables must be reported in a study. In ResolveMass Extractables and Leachables Testing, this threshold helps ensure that even the smallest potential contaminants are detected and evaluated for toxicological relevance.
Yes. ResolveMass Extractables and Leachables Testing supports multi-matrix analysis, including plastics, rubbers, metals, and combination medical devices. This versatility enables a complete understanding of how different materials may contribute to leachable profiles across various applications.
All E&L studies at ResolveMass undergo GLP-compliant validation and multi-level peer review. This ensures the highest scientific accuracy, complete traceability, and confidence in every report generated under ResolveMass Extractables and Leachables Testing protocols.
References
- Rozio, M. G. (2025). Correcting detection and quantitation bias in extractables and leachables testing. Journal of Pharmaceutical Analysis, 15(2), 123–134. https://doi.org/10.1016/j.jpha.2025.04.004
- United States Pharmacopeial Convention. (n.d.). Extractables and leachables. Retrieved October 10, 2025, from https://www.usp.org/impurities/extractables-and-leachables
- Balfour, H. (2022, April 29). Advancing extractables and leachables testing. European Pharmaceutical Review. https://www.europeanpharmaceuticalreview.com/article/170814/advancing-extractables-and-leachables-testing/
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