Introduction: Why Addressing Leachables Risk in a Biologic Vial System is Crucial
In 2025, the biopharmaceutical industry continues to face increasing regulatory scrutiny regarding the safety of container-closure systems. For injectable biologics, leachables risk in a biologic vial can compromise product stability, patient safety, and regulatory approval timelines. This case study highlights how ResolveMass Laboratories Inc., a leading E&L Testing CRO, helped a global biologics company identify and mitigate leachables risk in their new vial system through a comprehensive Extractables & Leachables (E&L) strategy.
From predictive modeling to controlled extraction studies and regulatory-grade leachables assessments, our end-to-end service offering exemplifies the proactive and science-backed approach ResolveMass brings to the table.
Learn more about our capabilities at Extractables & Leachables Testing.
Project Background: High Stakes for a High-Value Biologic
The client, a multinational biologics firm, was preparing to launch a recombinant monoclonal antibody in a pre-filled vial presentation. During final formulation stability studies, concerns emerged about potential leachables risk in the biologic vial—especially due to the interaction of the rubber stopper and plastic overwrap with the acidic protein formulation.
Regulatory bodies such as the FDA and EMA have set stringent requirements for leachables profiling in biologics, particularly when dealing with sensitive or chronic treatments. The company needed:
- A proven E&L Testing CRO with biologics experience
- A detailed extractables & leachables testing plan
- Support for documentation in their BLA submission
Phase 1: Extractables Assessment to Preempt Leachables Risk
The first step was a targeted extractables study of all container-closure components:
- Elastomeric rubber stopper
- Glass vial
- Polymeric overwrap
- Aluminum crimp cap
Using orthogonal extraction solvents and worst-case conditions, we performed GC-MS, LC-MS, and ICP-MS screening to detect and identify potential extractables that could contribute to leachables risk in a biologic vial system.
Our study revealed over 20 extractable compounds, including:
- Phenolic antioxidants
- Plasticizers (phthalates)
- Oligomers from rubber degradation
These findings informed the custom leachables testing protocol, establishing baseline risks specific to the client’s product-contact materials.
Read more about our methods at E&L Testing Services.
Phase 2: Biologic-Specific Leachables Simulation and Testing
To evaluate leachables risk in a biologic vial, we recreated real-world storage conditions:
- 40°C/75% RH accelerated aging
- Standard refrigerated storage at 2-8°C
- Light exposure simulations
Our analytical team used:
- LC-MS/MS for non-volatile leachables
- GC-MS for volatile organic compounds
- ICP-MS for elemental impurities
During a 6-month leachables study, trace levels of two compounds from the stopper migrated into the drug product matrix, including:
- 2,6-Di-tert-butylphenol (antioxidant)
- A phthalate-derived plasticizer
Though both were under the PQRI safety thresholds, the client opted to switch stopper materials to proactively mitigate leachables risk in the biologic vial.
Regulatory Support: BLA Filing and Justification
ResolveMass Laboratories supplied a full technical package for the client’s Biologics License Application (BLA), including:
- Risk-based leachables evaluation strategy
- Justification of analytical methods
- Safety assessment per ICH Q3D and PQRI guidelines
This comprehensive documentation and scientific defensibility helped the client:
- Address FDA queries preemptively
- Avoid additional testing post-submission
- Ensure uninterrupted product development timelines
Looking for compliant and reliable support? Contact ResolveMass
Why Choose ResolveMass as Your E&L Testing CRO?
When it comes to biologics, we know what’s at stake. Here’s why leading pharma companies choose ResolveMass as their E&L Testing CRO:
- In-house expertise in biocompatibility and material science
- Specialized leachables simulation for protein therapeutics
- Ultra-sensitive LC-MS, GC-MS, and ICP-MS capabilities
- Customized study design and fast turnaround
Whether it’s addressing leachables risk in a biologic vial, injectable cartridge, or a new delivery system, we bring precision, speed, and compliance.
Explore our full range of solutions at Extractables & Leachables Testing.
Outcome: Safer Product, Smoother Launch
With a new stopper material and a validated leachables profile, the client successfully submitted their BLA. FDA reviewers acknowledged the robustness of the leachables study and accepted the proposed strategy without objections. More importantly, the company entered the commercial phase with confidence that their leachables risk in the biologic vial had been proactively addressed.
ResolveMass Laboratories continues to serve as their ongoing E&L Testing CRO partner for other injectable products in their pipeline.
“ResolveMass gave us the confidence and technical depth we needed to navigate complex leachables risk in our biologic vial system.”
Conclusion: Address Leachables Risk in a Biologic Vial Before It’s Too Late
If your biologic formulation is delivered in a vial, pre-filled syringe, or device system, the leachables risk in a biologic vial cannot be ignored. This case study shows how proactive testing, expert study design, and the right CRO partner can save time, money, and regulatory headaches.
Let ResolveMass Laboratories help you eliminate the guesswork. Work with an E&L Testing CRO that leads with science and supports your success.
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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.
We have PhD level scientist who share this knowledge to you so that you can excel in your impurity identification project. This guide will help you understand all the relevant technical aspects, still if you need more help to understand more in your impurity identification, feel free to book a free consultation with our scientist for your project.
REFERENCES
- Thomas F. Understanding Evolving E&L Regulations. In the Lab eNewsletter. 2020 Jan 8;15(1).
- Vas G, Fleck L, Comstock K, Cole J. Extractable and leachable testing for pharmaceutical packaging, finished pharmaceutical products, and medical devices: an analytical perspective.
- 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.
