Glass Syringes: Testing and Performance Requirements for Connectivity with Needles and Other Devices (DRAFT)
This guidance addresses connectivity issues between glass syringes and connecting devices (needles, needleless luer connectors, adapters, and transfer units). It applies to: - Needleless glass syringes prefilled with drug/biological products - Empty glass syringes co-packaged with drug/biological products and/or connecting devices - Empty glass syringes for use with marketed drugs/biological products
This is a draft guidance. Not for implementation.
What You Need to Know? 👇
What are the key connectivity issues between glass syringes and connecting devices that FDA has identified?
FDA has documented adverse events including syringe tips breaking upon injection, needles detaching during injection, and syringes breaking or jamming IV lines when certain glass syringes are used with connecting devices like needleless luer connectors.
Why is conformity to ISO 11040-4 alone insufficient for glass syringe approval?
ISO 11040-4 has undefined key dimensions including glass syringe nozzle internal diameter, nozzle wall thickness, and barrel neck curvature. These missing specifications can prevent proper connectivity with ISO 594-2 compliant connecting devices, leading to safety issues.
What additional testing does FDA recommend beyond ISO 11040-4 compliance for glass syringes?
FDA recommends functional performance testing including seal integrity, glide force, break force, connectivity testing with various devices, human factors testing, biocompatibility assessment, and sterilization validation to ensure proper interoperability with connecting devices.
What are the recommended design modifications to improve glass syringe connectivity?
FDA suggests using bonded needles with sharps protection, designing glass syringes with internal dimensions ensuring connectivity to connecting devices, or developing dedicated dual connections between glass syringes and specific connecting devices for co-packaging applications.
How are prefilled glass syringes regulated by FDA from a combination product perspective?
Prefilled glass syringes are combination products under 21 CFR Part 3. They’re assigned to CDER or CBER as lead centers based on primary mode of action and submitted under IND, BLA, NDA, or ANDA pathways.
What early interaction opportunities does FDA recommend for glass syringe developers?
FDA encourages joint meetings with involved centers (CBER/CDER and CDRH) to discuss proposed connectivity solutions. Developers should outline steps to ensure glass syringe connectivity when connected to various devices before submission preparation.
What You Need to Do 👇
Recommended Actions
- Evaluate design options:
- Consider bonded/staked needles with sharps protection
- Design internal dimensions ensuring connectivity
- Develop dedicated dual connections if needed
- Prepare testing documentation:
- Dimensional conformance data
- Design verification and validation data
- Functional performance testing results
- Biocompatibility data
- Sterilization validation
- Human factors testing results
- For prefilled/co-packaged syringes:
- Conduct additional performance testing with actual drug/biologic
- Evaluate product-specific requirements
- Address drug-device compatibility
- Consider early interactions with FDA through joint meetings with relevant centers
- Ensure proper documentation of all testing with objectives, methods, acceptance criteria, and results
Key Considerations
Non-clinical testing
- Seal Integrity Testing for liquid leakage, air ingress, and dye ingress
- Mechanical testing: glide force, break force, separation force, unscrewing torque
- Assembly testing: ease of assembly, resistance to overriding
- Performance testing: stress cracking, graduation markings validation, dead space
- Coring needle test
- Connectivity testing with other necessary devices
- Injection force testing
- Tip cap removal force testing
- Piston seal blowback testing
Human Factors
- Human factors testing and risk analysis of use errors
- Hazard analysis identifying use-related risks including medication errors
- Design validation of user interface
Biocompatibility
- Conformance to ISO 10993 with physicochemical, analytical, and biological testing
Safety
- Performance testing of anti-needlestick mechanisms
- System integrity demonstration throughout product shelf-life
- Sterilization validation
Other considerations
- Dimensional conformance to ISO standards
- Design verification and validation for critical connectivity features
- For prefilled syringes: performance testing with actual drug/biological product
- For dual-chamber syringes: specific testing for lyophilization, system integrity, reconstitution process
Relevant Guidances 🔗
- Piston Syringes and Accessories - Review Requirements and Testing Specifications for 510k Submissions
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
- Applying Human Factors Engineering and Usability Engineering to Medical Devices
- Human Factors Information Needed in Medical Device Marketing Submissions (Draft)
Related references and norms 📂
- ISO 11040-4: Prefilled Syringes - Part 4: Glass barrels for injectables
- ISO 594-2: Conical fittings with 6% (Luer) taper - Lock fittings
- ISO 10993: Biological Evaluation of Medical Devices
- ISO 11135: Sterilization of Health Care Products - Ethylene Oxide
- ISO 11137: Sterilization of Health Care Products - Radiation