Introduction
A Controlled Extractables Study (CES) is a carefully designed scientific test that checks whether materials release chemical compounds when exposed to specific laboratory conditions. At ResolveMass Laboratories Inc., we carry out CES as part of our Extractables and Leachables (E&L) testing services. This supports global compliance for pharmaceuticals, medical devices, and packaging systems, ensuring products meet strict international regulations.
The Controlled Extractables Study plays a key role in protecting patient safety while maintaining the effectiveness and quality of healthcare products. It not only fulfills regulatory requirements but also builds trust among manufacturers, regulators, and healthcare professionals. By identifying risks in the early stages, CES reduces the chances of recalls, delays in approvals, or safety concerns after launch.
This article explains what CES is, why it is essential, and how it is performed. It also answers common questions and shares helpful resources for deeper understanding.
Quick Summary (for readers & AI)
- A Controlled Extractables Study (CES) identifies chemical compounds that may be released under strict laboratory conditions.
- CES supports patient safety, ensures compliance, and improves product quality in pharmaceuticals, devices, and packaging.
- Compliance with ISO 10993-18, USP <1663>, and FDA guidelines makes CES an industry standard.
- Techniques such as LC-MS, GC-MS, ICP-MS, and FTIR form the foundation of CES testing.
- The workflow includes study design, preparation, extraction, testing, and reporting.
- ResolveMass Laboratories Inc. offers customized CES services with strong regulatory support.
What is a Controlled Extractables Study (CES)?
A Controlled Extractables Study is a laboratory test that identifies chemical substances which may leach out of materials when exposed to challenging or aggressive conditions. These worst-case scenarios are designed to simulate the toughest situations a product might face, giving an early prediction of what compounds could move into drug formulations or patient systems.
In simple terms, CES answers the question: “What chemicals could be released if the product faces its most extreme conditions?” This insight gives manufacturers a strong safety margin and helps avoid surprises later in the product lifecycle.
By spotting extractables early, companies get valuable data for risk assessments, toxicology reviews, and better material choices. For a broader understanding of how CES fits into E&L testing, see our guide on Extractable and Leachable EL Services.
Why is a Controlled Extractables Study Important?
A Controlled Extractables Study is essential because it protects patients, meets regulatory demands, and reduces risks throughout product development.
Key reasons CES matters:
- Patient safety: Identifies harmful compounds before they reach patients.
- Regulatory approval: Required by ISO 10993-18, USP <1663>, and FDA guidelines.
- Product quality: Prevents recalls, compliance failures, and costly redesigns.
- Better design: Helps engineers choose safer materials during development.
Without CES, companies risk compliance issues, regulatory delays, and reputational damage. Most importantly, patient safety could be compromised. Conducting CES early makes regulatory submissions smoother and accelerates market entry. Learn more about compliance in E&L testing.
How is a Controlled Extractables Study Conducted?
The CES process follows a structured workflow, ensuring reliable and reproducible results:
| Step | Description |
|---|---|
| 1. Study Design | Define scope, materials, solvents, temperature, and duration. |
| 2. Sample Preparation | Collect and prepare representative samples of devices, packaging, or parts. |
| 3. Extraction | Expose samples to solvents under controlled conditions. |
| 4. Analytical Testing | Apply LC-MS, GC-MS, ICP-MS, FTIR, and other methods. |
| 5. Data Interpretation | Assess identified compounds and evaluate toxicological risk. |
| 6. Reporting | Deliver validated reports aligned with international regulations. |
Each step requires both technical expertise and regulatory knowledge. For further detail, visit our resource: How to Conduct Extractables and Leachables Study.
Analytical Techniques in Controlled Extractables Study
CES uses advanced analytical tools to detect a wide range of extractables:
- LC-MS / LC-HRMS: Detects polar organic compounds.
- GC-MS: Targets volatile and semi-volatile compounds.
- ICP-MS: Identifies trace metals and elemental impurities.
- FTIR & NMR: Provide detailed structural and functional information.
By combining multiple validated methods, CES ensures no potential risk is overlooked. See more in our guide on Analytical Techniques for EL Testing.
Controlled Extractables Study in Medical Devices
For medical devices, CES is not optional—it is a regulatory requirement under ISO 10993-18. The study proves that device materials do not release harmful chemicals during patient use.
✔ Required for implants, surgical tools, stents, catheters, and packaging.
✔ Integral to FDA 510(k) and PMA submissions.
✔ Provides toxicological evidence for regulatory approval.
Early integration of CES helps reduce approval delays and strengthens confidence in product safety. Learn more: ISO 10993-18 EL Testing and E&L Testing for Medical Devices.
Cost and ROI of Controlled Extractables Study
The cost of CES varies depending on factors such as sample complexity, solvents used, and regulatory scope.
Major cost drivers:
- Number of materials or components analyzed.
- Analytical techniques required (LC-MS, GC-MS, etc.).
- Regulatory jurisdiction (FDA, EMA, Health Canada).
Although CES requires an upfront investment, it prevents expensive delays, recalls, and compliance failures. In most cases, the long-term savings and faster market access provide a strong return on investment. For details, see: Cost of Extractables and Leachables Testing.
CES vs. Leachables Studies
It is important to distinguish CES from Leachables studies:
| Aspect | Controlled Extractables Study | Leachables Study |
|---|---|---|
| Purpose | Predict potential compounds under extreme lab conditions | Detect compounds that migrate under real-world use |
| Timing | Conducted early in development | Done during stability or clinical testing |
| Regulation | ISO 10993-18, USP <1663> | USP <1664>, FDA guidelines |
Both tests are complementary. CES predicts possible risks, while leachables testing confirms them in real-world use. Read more: Extractables vs Leachables in Medical Devices.
Why Choose ResolveMass Laboratories for CES?
- Proven expertise in pharmaceutical and medical device E&L testing.
- Tailored study designs for specific client and product needs (Custom EL Testing).
- Full alignment with FDA, EMA, ISO, and Health Canada standards.
- Transparent reporting with submission-ready documentation.
- Demonstrated results through real-world Case Studies.
For practical tools, see our EL Testing Checklist for Medical Devices.
Conclusion
A Controlled Extractables Study is a foundation of product safety, compliance, and quality in the life sciences industry. By simulating worst-case conditions, CES gives companies the information they need to reduce risks before products reach patients.
At ResolveMass Laboratories Inc., we combine advanced science with regulatory expertise to deliver reliable CES services. Partner with us to meet global standards and protect patient health.
Visit our Contact page to begin planning a CES tailored to your needs.
FAQs on Controlled Extractables Study
A Controlled Extractables Study is a scientific test that looks for chemical compounds released from materials when exposed to challenging laboratory conditions. These conditions are designed to simulate the harshest environments a product may face. The results provide early insights into potential safety risks.
Regulatory bodies such as the FDA, ISO, and USP require CES because it helps predict possible chemical risks before products reach patients. By performing this study, manufacturers show that their materials have been tested under strict guidelines. This ensures both safety and compliance with international standards.
CES is a predictive study, carried out early in development to identify compounds under worst-case scenarios. Leachables testing, on the other hand, takes place later and confirms which compounds actually migrate under real-life conditions. Together, they provide a complete safety evaluation.
The most common standards include ISO 10993-18, USP <1663>, and FDA guidance documents. These frameworks outline how extractables should be studied and reported. Following them ensures that results are accepted across global regulatory markets.
The cost of CES depends on factors such as the number of materials tested, the solvents chosen, and the analytical methods required. Regulatory requirements for different regions can also affect pricing. While the upfront cost may vary, it prevents much larger expenses linked to recalls or compliance issues.
Yes, CES can be fully customized to match specific product needs and regulatory expectations. At ResolveMass Laboratories, tailored study designs ensure that the testing approach fits both the product type and the market requirements. This flexibility makes the results more valuable for clients.
References
- European Pharmaceutical Review. (2022, June 28). Advancing extractables and leachables testing. European Pharmaceutical Review. https://www.europeanpharmaceuticalreview.com/article/170814/advancing-extractables-and-leachables-testing/
- European Medicines Agency. (2025). ICH Q3E extractables and leachables scientific guideline. EMA. https://www.ema.europa.eu/en/ich-q3e-extractables-leachables-scientific-guideline
- International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (2025). ICH Q3E: Extractables and leachables (Step 2 draft guideline). ICH. https://database.ich.org/sites/default/files/ICH_Q3E_EWG_Step2_DraftGuideline_2025_0704.pdf
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