INTRODUCTION
Outsourcing to a U.S.-based Extractables and Leachables (E&L) testing laboratory in the United States helps pharmaceutical and biotech companies speed up regulatory timelines because U.S. labs understand FDA expectations, provide faster communication, and deliver compliant documentation without delays. For companies seeking rapid approvals, a U.S. outsourcing partner such as ResolveMass Laboratories Inc. becomes instrumental in navigating stringent regulatory processes.
This blog explains in detail why outsourcing E&L studies is a strategic advantage, how it accelerates submissions, and what industry-specific benefits biotech and pharma teams gain.
SUMMARY
- Outsourcing to a U.S.-based Extractables and Leachables (E&L) testing laboratory accelerates regulatory timelines through FDA-aligned workflows and validated analytical methods.
- U.S. laboratories provide rapid turnaround, deeper regulatory familiarity, and specialized instrumentation that reduces the risk of deficiencies.
- Expert study directors, toxicologists, and analytical chemists ensure compliant study design aligned with ICH Q3E, USP <1663>, and <1664>.
- Outsourcing frees internal teams from labor-intensive method development, validation, and documentation.
- U.S.-based E&L teams optimize risk assessment, chemical identification, and threshold evaluations for smoother approvals.
- Comprehensive reporting, trace-level identification, and robust justifications help shorten overall review time.
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1. FDA-ALIGNED STUDY DESIGN STARTS RIGHT AWAY
A U.S.-based Extractables and Leachables (E&L) testing laboratory immediately accelerates timelines by designing studies fully aligned with U.S. FDA expectations. Unlike general-purpose labs, U.S. E&L facilities follow domestic regulatory interpretations daily, ensuring no gaps in:
- Extraction conditions
- Migration simulation
- Analytical thresholds (AET calculation)
- Reporting format
- Material characterization
- Toxicological risk assessment
Key Advantages of FDA-Aligned Design
- Correct selection of solvents, temperatures, and durations for extractables studies
- Proper simulation of worst-case product–packaging interactions
- Appropriate identification and quantification of volatiles, semi-volatiles, and non-volatiles
- Selection of leachables time points aligned with FDA expectations
This ensures early-phase work is valid for final submission, preventing costly restarts.
2. FAST INITIATION OF E&L WORK DUE TO READY FRAMEWORKS
U.S. E&L laboratories maintain pre-validated frameworks, allowing them to begin studies within days. Their workflows already include:
- Standardized extraction protocols
- Predefined analytical screening conditions
- Established unknown identification workflows
- Risk assessment templates
- SOPs for sample preparation and stability simulation
Why This Matters
In-house teams often spend weeks preparing methods, calibrating equipment, or training personnel. Outsourced E&L teams skip all of these steps, lowering startup times dramatically.
3. ADVANCED INSTRUMENTATION REDUCES TOTAL STUDY DURATION
A leading U.S.-based Extractables and Leachables (E&L) testing laboratory typically houses high-end instrumentation capable of identifying compounds down to sub-ppb levels.
Commonly Used Systems
- LC-MS/MS (Triple Quadrupole) for non-volatile targeted quantification
- UHPLC-QTOF / Orbitrap HRMS for unknown identification
- GC-MS and GC-MS/MS for volatile/semi-volatile analysis
- GC-HRMS for detecting trace-level compounds
- ICP-MS for elemental leachables and extractable metals
Estimated Time Savings
| Step | In-House Timeline | U.S. Outsourced Lab Timeline |
|---|---|---|
| Method Development | 4–6 weeks | 1–2 weeks |
| Extractables Study | 3–4 weeks | 1–2 weeks |
| Leachables Study | 4–8 weeks | 2–4 weeks |
| Reporting | 3–6 weeks | 1–2 weeks |
These reductions come from instrument availability, high-throughput workflows, and dedicated E&L teams.
4. CROSS-FUNCTIONAL EXPERTISE SUPPORTS FASTER DECISION-MAKING
Outsourcing to a U.S.-based Extractables and Leachables (E&L) testing laboratory gives companies immediate access to multidisciplinary expertise:
Available Expertise Includes:
- Analytical chemists
- Extractables specialists
- Leachables monitoring chemists
- Toxicologists
- Materials scientists
- E&L study directors
- Regulatory reviewers
Each discipline contributes to faster interpretation of results and faster refinement of study strategies.
5. LOWER RISK OF REGULATORY DEFICIENCIES AND REJECTIONS
FDA deficiencies in E&L reports often lead to:
- Resubmission cycles
- Additional testing
- Delayed commercial launch
- Increased costs
U.S. E&L laboratories understand the specific documentation style and depth that FDA reviewers expect, including:
- Clear AET justification
- Mass spectral interpretation
- Unknown compound elucidation
- ICH Q3E toxicological risk assessments
- Threshold of toxicological concern (TTC) evaluations
Most Common Deficiencies Prevented
- Missing worst-case simulation rationale
- Incomplete extractables profiles
- Poor chromatographic data justification
- Missing leachables time-point evaluation
- Inadequate toxicological summaries
6. SUPERIOR COMMUNICATION AND REDUCED TURNAROUND DELAYS
Time-zone alignment and cultural familiarity significantly speed communication. A U.S.-based E&L testing laboratory ensures:
- Faster responses to technical inquiries
- Real-time clarification of data
- Quicker decision-making
- No delays caused by international coordination
This is particularly important during:
- Investigations
- Out-of-spec (OOS) evaluations
- Extractables-to-leachables traceability analysis
Better communication = faster regulatory readiness.
7. OUTSOURCING ALLOWS INTERNAL TEAMS TO FOCUS ON CMC & DEVELOPMENT
E&L testing involves:
- Designing extraction schemes
- Preparing solvents
- Conducting multi-phase testing
- Running chromatographic sequences
- Identifying unknowns
- Generating toxicology reports
These tasks consume significant internal resources. Outsourcing to a U.S.-based Extractables and Leachables (E&L) testing laboratory frees internal scientific teams to focus on:
- Formulation development
- CMC activities
- Manufacturing optimization
- Stability testing
- Submission compilation
8. U.S. LABS PROVIDE SCALABILITY FOR COMPLEX E&L PROGRAMS
Large E&L programs often require hundreds of analyses. U.S. outsourcing labs maintain scalable infrastructure including:
Scalable Capacities
- Multiple LC-MS/MS, GC-MS, and ICP-MS units
- Parallel extraction stations
- Dedicated migration chambers
- Automated sample preparation units
This allows the CRO to handle:
- Multiple container-closure systems simultaneously
- Entire biologics platform E&L strategies
- Multi-material evaluations (glass, elastomers, stainless steel, tubing, polymers)
9. DEEP UNDERSTANDING OF U.S. REGULATORY NUANCES
U.S.-based laboratories interact frequently with:
- FDA reviewers
- U.S. pharmacopeial experts
- Domestic quality auditors
This gives them nuanced understanding of:
- FDA expectations for quantitation ranges
- Recommended identification criteria
- Handling of “unidentified peaks”
- Justification requirements for analytical thresholds
- Migration modeling approaches
Such insights directly accelerate approvals.
10. WHAT A U.S. E&L LABORATORY TYPICALLY PROVIDES
To replace the earlier link sections, here is the deep-level detail you requested:
A. What U.S.-Based E&L Testing Includes
A comprehensive U.S. E&L program typically includes:
- Extractables screening under exaggerated conditions
- Migration (leachables) studies under real-time and accelerated conditions
- TOC screening
- GC-MS profiling of VOCs/SVOCs
- LC-MS profiling of non-volatiles
- ICP-MS profiling of elemental impurities
- Full unknown investigation workflows
- Material safety risk assessments
- Toxicology threshold justifications
- Impurity carry-over evaluation
- Batch-to-batch variability studies
B. What U.S. Outsourced Forced Degradation Programs Typically Cover
This replaces the forced degradation link:
- Stress conditions: acid, base, oxidation, thermal, photolysis
- Identification of degradants
- Understanding packaging–product interaction
- Stability-indicating method development
- Leachable–degradant cross-interference evaluations
This combined E&L + forced degradation expertise ensures strong regulatory compliance.
CONCLUSION
Outsourcing to a U.S.-based Extractables and Leachables (E&L) testing laboratory in the United States significantly accelerates regulatory timelines by providing FDA-aligned study design, cutting-edge instrumentation, expert scientific staff, rapid turnaround, and detailed risk assessments. These capabilities reduce deficiencies, prevent rework, and give regulatory reviewers exactly the level of detail they expect.
For pharmaceutical, biotech, and medical device companies, the strategic decision to outsource E&L testing to U.S. experts results in faster submissions, more reliable results, and smoother market approvals.
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FAQs on Outsourcing to a U.S.-Based Extractables and Leachables (E&L)
Outsourcing E&L testing to a U.S.-based laboratory is beneficial because U.S. labs design their studies specifically around FDA expectations and interpretations of ICH Q3E, USP <1663>, and <1664>. This means the extraction conditions, solvent choices, simulation durations, identification criteria, and documentation structure already match the standards FDA reviewers expect to see.
U.S. labs routinely support IND, NDA, ANDA, and BLA submissions, so they understand what constitutes an acceptable AET justification, how to present mass spectral matches, and how to generate risk assessments that withstand regulatory scrutiny. This drastically reduces the risk of FDA issuing deficiency letters, which often delay product approval by months. Additionally, U.S. labs are familiar with recent industry case studies, trends in FDA feedback, and common reviewer objections — allowing them to prevent issues proactively rather than reactively.
A U.S.-based E&L laboratory offers a comprehensive suite of analytical and toxicological services that cover the entire extractables and leachables lifecycle. Typical services include:
-Volatile analysis (GC-MS): Detection of solvents, monomers, processing residues, and VOCs.
-Semi-volatile analysis (GC-MS/MS): Identification of antioxidants, oligomers, and additives.
-Non-volatile analysis (LC-MS/MS, UHPLC-QTOF): Detection of polymeric additives, degradation products, plasticizers, and unknown species.
-Elemental impurities (ICP-MS): Screening and quantification of metals originating from manufacturing equipment, glass, elastomers, or stainless-steel components.
-Migration (Leachables) studies: Real-time and accelerated studies that simulate actual product–packaging interactions over shelf life.
-Material characterization: Polymer identification, elastomer composition profiling, and evaluating extractive potential of device components.
-Toxicological risk assessment: Component-level risk evaluation based on AET/TTC, PDEs, mutagenicity, and TTC-driven safety thresholds.
-Unknown identification workflows: High-resolution mass spectrometry to elucidate unknown peaks using fragmentation patterns, isotopic signatures, and spectral libraries.
These services help pharmaceutical and biotech sponsors meet all analytical and safety requirements for container-closure systems and combination products.
Yes. Most U.S.-based laboratories were early adopters of ICH Q3E principles even when they were in the draft stage. Because the FDA is a founding member of ICH, U.S. labs follow the guideline closely and align their study designs around Q3E’s structured approach, which includes:
-Clear definition of materials and system boundaries
-Detailed extractables study design with worst-case conditions
-Creation of an Analytical Evaluation Threshold (AET)
-Toxicological evaluation using TTC or PDE-based thresholds
-Structured reporting aligned with ICH modules
Additionally, U.S. labs incorporate the FDA’s preferred style of data presentation, including chromatographic overlays, mass accuracy tables, fragmentation justification, and toxicological summaries. This experience translates to smoother regulatory review and fewer requests for clarification.
Absolutely. U.S.-based E&L labs typically provide end-to-end toxicological support, which is essential for determining whether an identified extractable or leachable poses a safety risk. Typical toxicology services include:
-TTC-based evaluation: Determines if detected impurity levels fall below the threshold of toxicological concern for specific dosage forms.
-Permitted Daily Exposure (PDE) calculations: For compounds with known toxicology data.
-Structure–Activity Relationship (SAR): Predicts the toxicological impact of compounds lacking historical safety data.
-DB-ALERT or in silico mutagenicity assessment: Screens compounds for mutagenic structural alerts.
-Risk ranking and justification: Summaries for regulatory reviewers explaining why certain compounds do or do not require further qualification.
-Safety margin evaluation: Comparing estimated patient exposure to acceptable limits set by ICH, USP, or FDA.
This ensures that identified leachables are scientifically evaluated for toxicity and regulatory acceptance.
E&L studies cover a wide range of materials used in pharmaceuticals, biologics, and medical devices. Common materials evaluated include:
-Polymers: PP, PE, PVC, cyclic olefins (COP/COC), PET, PTFE
-Elastomers: Butyl rubber, silicone, EPDM, latex-free synthetic rubbers
-Glass: Borosilicate vials, cartridges, ampoules
-Adhesives & coatings: UV-curable adhesives, resin coatings, epoxy layers
-Tubing & connectors: TPE tubing, silicone tubing, stainless-steel connectors
-Medical-grade plastics: Polycarbonate, ABS, polyurethane, nylon
Each material has a unique extractive profile, so tailored extraction conditions and analytical techniques are used to capture the full chemical fingerprint.
Several industries rely heavily on E&L testing, including:
-Injectable drugs: Sensitive formulations where even trace leachables can compromise safety.
-Biologics: Proteins and mAbs that are highly susceptible to interaction with packaging.
-Inhalation therapies: Strict safety requirements for respiratory exposure.
-Ophthalmic products: Ultra-low thresholds for impurities due to direct eye contact.
-Transdermal systems: Packaging adhesives and plasticizers need thorough evaluation.
-Medical devices and combination products: Pre-filled syringes, pens, infusion systems, and implantables.
These industries face rigorous regulatory scrutiny, making expert E&L support essential.
Most U.S. E&L laboratories begin projects within 3–5 business days once the proposal is signed and samples are received. Their readiness is due to:
-Established SOPs
-Pre-validated extraction conditions
-In-house toxicology teams
-Dedicated E&L project managers
-High instrumentation capacity
This immediate initiation is especially beneficial for time-sensitive IND, NDA, or BLA programs where delays can affect clinical or commercial timelines.
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Reference
- Balfour, H. (2022, April 29). Advancing extractables and leachables testing. European Pharmaceutical Review. https://www.europeanpharmaceuticalreview.com/article/170814/advancing-extractables-and-leachables-testing/
- 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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