✅ Summary of Key Takeaways:
- USP <1663> and <1664> provide critical guidance for extractables and leachables (E&L) testing of medical devices and drug packaging.
- These guidelines ensure patient safety and support regulatory approval of combination products.
- A robust E&L workflow includes material characterization, analytical method development, toxicological risk assessment, and reporting.
- Failure to adhere to E&L standards can lead to regulatory delays or product recalls.
- ResolveMass Laboratories Inc. offers customized and compliant E&L testing services across all device classes.
- Includes FAQs, resources, and direct links to our services and expertise.
🧪 Introduction: Why USP <1663>, <1664> Extractables Leachables Matter for Medical Device Approval
The USP <1663>, <1664> Extractables Leachables guidelines set the standard for how to evaluate chemical risks in drug packaging and delivery systems. Here’s a simple breakdown:
- USP <1663> focuses on extractables—chemicals that might be released from packaging or device materials when tested under tough conditions.
- USP <1664> covers leachables—substances that actually migrate into the drug during normal storage or use.
These processes are especially important for items like syringes, inhalers, and other combination devices. Following these guidelines doesn’t just help meet regulations—it shows a strong commitment to patient safety and global quality standards.
Explore our E&L testing solutions:
🔗 Extractables and Leachables Testing
🔗 E&L Testing for Medical Devices
🧠 What are USP <1663> and <1664>?
| Guideline | Focus Area | Key Objectives |
|---|---|---|
| USP <1663> | Extractables | Identify potential organic and inorganic substances that may migrate from container-closure systems or medical devices under exaggerated conditions. |
| USP <1664> | Leachables | Evaluate substances that actually leach into the drug product under normal use or accelerated conditions. |
These standards are tailored for use with drug packaging, delivery systems like inhalers, and injectable containers. By following these workflows, manufacturers can better identify and assess the potential health risks of chemicals that may come into contact with the medication or the patient.
Explore USP guideline-aligned workflows:
🔗 Custom E&L Testing Programs
🔗 E&L Testing for Inhalation Products
E&L Testing Workflows Based on USP <1663>, <1664> Extractables Leachables
🔬 Step 1: Material and Component Characterization
The first step is understanding what the device is made of. This includes identifying polymers, coatings, adhesives, and any added chemicals. Knowing this helps us predict what might be extracted or leached later in the process.
We also trace the material sources, which improves transparency and ensures consistency across production batches.
🧪 Step 2: Extractables Testing (USP <1663>)
Next, we put the materials through stress conditions like heat, solvents, or high pressure. This helps uncover any chemicals that could be released from the materials. We use advanced tools like GC-MS, LC-MS, ICP-MS, and more to detect both known and unknown compounds.
The result is a complete extractable profile for each material used.
🧫 Step 3: Simulated Use Conditions
Now, we simulate how the device will actually be used. We immerse parts in the real drug product or a safe substitute, under realistic storage or handling conditions. This step helps predict how materials will behave in real-world situations—whether that’s shaking, high humidity, or extended storage.
📉 Step 4: Leachables Testing (USP <1664>)
Using long-term storage or accelerated aging, we test to see which chemicals actually make their way into the drug. These results are important for evaluating risks to patients and meeting regulatory demands.
Our findings are linked to usage data to ensure real-life exposure levels are fully understood.
🧠 Step 5: Toxicology Review
The test results are carefully reviewed by experts who assess the risks based on safety thresholds such as SCT and TTC. They also evaluate the potential for cancer, genetic effects, or other health-related concerns linked to any detected substances.
This step turns raw data into meaningful insights that show whether a product is safe to use.
📄 Step 6: Regulatory Documentation
The last step is putting everything into a clear, submission-ready report. We follow FDA, EMA, and Health Canada formats and include all the required data—compound lists, risk summaries, and full interpretations.
This helps speed up your approval process while ensuring every box is checked.
Get detailed insights:
🔗 E&L Testing and Patient Safety
🔗 FAQs on E&L Testing
Why USP <1663>, <1664> Extractables Leachables Testing Is Crucial
Using USP <1663>, <1664> Extractables Leachables testing isn’t just a formality—it’s key for:
- Regulatory Approval: Authorities now expect E&L data that matches these standards.
- Patient Safety: Protects users from harmful chemical exposure.
- Faster Market Launch: Clean, compliant reports help avoid delays in review.
- Lower Costs: Early risk detection reduces the need for costly fixes later.
- Trust and Transparency: Shows stakeholders that your product is high-quality and globally aligned.
ResolveMass ensures all data is solid, verified, and ready for submission—saving you time and reducing risks.
Learn more:
🔗 E&L Testing Services Overview
🔗 Cost of Extractables and Leachables Testing
Why Choose ResolveMass Laboratories?
Fully Validated Workflows
All our testing processes are built around USP <1663>, <1664> Extractables Leachables. From start to finish, your data is collected and reported with regulatory approval in mind.
Clear and Customized Reports
We don’t do one-size-fits-all. Each report is tailored to your specific product and submission type, including PMAs, NDAs, ANDAs, and 510(k)s.
Advanced Instruments and Facilities
Our labs use state-of-the-art technology like GC-MS, LC-MS/MS, ICP-MS, and UV-VIS. These tools help us deliver precise, reliable results on time.
Explore our portfolio:
🔗 Extractables and Leachables Full Service
🔗 Leachables in Medical Devices
Core Benefits of a Strong E&L Testing Strategy
| Benefit | What It Means |
|---|---|
| 🚀 Faster Approvals | Well-prepared reports help shorten review time. |
| 🧪 Reliable Data | Trusted results for ongoing product safety monitoring. |
| 🛡️ Regulatory Ready | Reduces chances of recalls or regulatory holds. |
| 🔍 Clear Sourcing | Track chemicals across your supply chain. |
| 💰 Cost Savings | Catch risks early to avoid delays and expensive rework. |
🔗 Understand E&L Testing Costs
Conclusion: Compliance Begins with the Right Testing
Whether you’re launching a new combination product or updating an existing delivery system, USP <1663>, <1664> Extractables Leachables testing should be a top priority. It supports safety, speeds up global submissions, and builds confidence with patients and regulators alike.
At ResolveMass Laboratories, we specialize in creating custom, fully validated E&L testing workflows. Our expert team, cutting-edge tools, and proven methods help your products succeed in every market.
Explore our services today:
🔗 Visit ResolveMass Labs
🔗 E&L Medical Device Testing
🔗 Custom E&L Plans
🔗 FAQs About E&L
📬 For consultation or sample testing, reach out:
🔗 Contact Us
Frequently Asked Questions About USP <1663>, <1664> Extractables Leachables
Not all medical devices require E&L testing. However, it is mandatory for combination products, drug delivery systems, inhalers, and any container-closure systems that come in contact with the drug. These products are closely regulated by agencies like the FDA, EMA, and Health Canada.
These guidelines provide a clear and standardized method for identifying, analyzing, and assessing chemical risks in drug-contacting components. By following them, manufacturers can ensure product safety, meet regulatory expectations globally, and streamline the approval process for new devices.
E&L testing uses advanced analytical tools like GC-MS, LC-MS/MS, ICP-MS, FTIR, UV-VIS, and Total Organic Carbon analysis. The choice of technique depends on the device materials and the type of chemicals being studied. These methods ensure accurate detection of both known and unknown compounds.
Yes, inhalation devices need extra attention because they deliver drugs directly to the lungs, which are highly sensitive. Therefore, USP <1663>, <1664> Extractables Leachables testing for these devices is done with stricter safety thresholds and more conservative risk assessments.
Absolutely. A toxicological risk assessment is a vital part of the E&L process. It evaluates the potential health risks of each identified chemical by comparing exposure levels to safety thresholds like SCT (Safety Concern Threshold) and TTC (Threshold of Toxicological Concern).
Yes, ResolveMass offers fully customized E&L testing solutions. Whether your device is a syringe, inhaler, implant, or other drug-device combination, we tailor the workflow based on material type, intended use, and target regulatory region to ensure complete compliance.
Some frequently detected leachables include plasticizers like phthalates, antioxidants, UV stabilizers, residual solvents, oligomers, and even trace metals. Each substance is assessed for potential toxic effects to ensure patient safety and product compliance.
The cost of E&L testing depends on the device complexity, number of components, regulatory requirements, and depth of analysis. ResolveMass offers flexible pricing options and provides detailed quotes based on your product’s specific needs and testing scope.
