Extractables and Leachables.
E&L Studies.
Safety for pharmaceutical packaging, process contact materials, and radiopharmaceutical cassettes.
Our Extractables & Leachables (E&L) studies ensure that container closure systems (CCS), single-use systems (SUS), process contact materials, and cassettes for the manufacture of radiopharmaceuticals do not release any dangerous substances. CUP Contract Labs offers a unique range of services: We conduct E&L studies with both radioactive pharmaceuticals and non-radioactive substances—GMP-compliant, precise, and regulatory-compliant.
What are extractables and leachables?
- Extractables: Packaging or production materials (e.g., tubing, vial stoppers, radiopharmaceutical cassettes) are extracted using suitable solvents. We then analyze the samples using LC-HRMS, GC-MS, HS-GC-MS, GC-MS after derivatization, and ICP-MS to identify migratable constituents.
- Leachables: The product is stored in direct contact with packaging, process materials, or radiopharmaceutical cassettes, sometimes under stress conditions. Analyses compared to a blank value show which substances actually migrate into the product.
Identification is performed using mass spectrometry databases, supplemented by a semi-quantitative concentration estimate.
Regulatory standards and guidelines.
Our extractables and leachables tests are based on international guidelines.
By integrating the new ICH Q3E Guideline, we ensure that our analyses meet the latest international expectations – from development to lifecycle management after market approval.
- CH Q3E (Draft, 2025) – new global guideline for E&L studies, risk-based approach with AET, SCT, and QT
- USP <1663> & USP <1664> – Extractables & Leachables studies
- USP <661> & USP <665> – Plastic packaging and single-use systems
- ISO 10993-18 – Chemical characterization in the biological evaluation of medical devices
- FDA guidelines – Regulatory requirements for E&L studies
- EMA guidelines – European standards for container closure systems
Expert voices
I find high-resolution mass spectrometry (LC-HRMS) particularly exciting. The measurement results are extremely precise and give us insights down to the molecular formula level. Depending on the product, packaging, or cassettes used, we sometimes find no leachables—in other cases, we find over 100 substances. This diversity makes every project unique.
Extractables & Leachables Study Workflow.
From risk assessment to regulatory-ready report.
The process begins with your request for an Extractables and Leachables (E&L) study. Based on initial information about the product, packaging system, and development stage, we evaluate the scope of the study and identify the relevant regulatory framework.
To ensure structured planning, we collect detailed information on materials, packaging components, formulation, and manufacturing processes. These data form the basis for a risk-based assessment of potential material-derived impurities.
Our experts develop a risk-based study design tailored to the specific product and material system. Regulatory guidance such as USP <1663>, USP <1664>, and ICH Q3E is considered to ensure scientific and regulatory robustness.
Materials are investigated under defined worst-case extraction conditions to identify potential extractable compounds. These studies provide a comprehensive overview of substances that may migrate from packaging or device components into the pharmaceutical product.
Identified substances are analyzed using advanced analytical technologies including GC-MS, LC-MS/MS, and ICP-MS. These techniques allow reliable detection and characterization of volatile, semi-volatile, non-volatile, and elemental contaminants.
Based on the extractables results, targeted leachables studies are performed to determine which compounds actually migrate into the drug product under real storage and use conditions.
Detected compounds are evaluated with respect to patient exposure and toxicological relevance. Established thresholds such as SCT (Safety Concern Threshold), AET (Analytical Evaluation Threshold), and QT (Qualification Threshold) are applied.
You receive a comprehensive Extractables and Leachables study report including analytical data, risk evaluation, and regulatory documentation. The report can be used for regulatory submissions, quality documentation, and product approval processes.
CUP contract labs.
Your advantages.
As a reliable partner, we stand by your side.
- Unique: E&L analyses for radioactive and non-radioactive pharmaceuticals
- Specialization in radiopharmaceutical cassettes – experience with materials used in radiopharmaceutical manufacturing
- State-of-the-art analytics: LC-HRMS, GC-MS, HS-GC-MS, ICP-MS
- GMP-compliant documentation & risk analyses according to EMA and ICH-M7 guidelines
- Up-to-date regulatory expertise: Implementation of the new ICH Q3E guideline for global approvals
- Reliability: Fast measurements, well-founded evaluations for regulatory-compliant results
Practical example:
In a stability study, noticeable peaks appeared in the HPLC-DAD measurement. Since they were not API-related, they were identified as leachables and estimated semi-quantitatively. This clarified the source of unexpected impurities and secured the approval dossier.
Key facts.
- Accuracy: semi-quantitative estimation, worst-case oriented; critical substances are specifically quantified using standards
- Typical samples: vial stoppers, tubing, radiopharmaceutical cassettes, finished pharmaceutical products
- Areas of application: pharmaceutical products, process contact materials, container closure systems, single-use systems
- Speed: Fast measurements; time-consuming evaluation (e.g., up to 4 hours per sample in LC-HRMS)
- Regulatory up-to-date: Implementation of the new ICH Q3E Guideline
Customer Voices
Again, thank you so much and we enjoy working alongside you and your team.
