Technical Considerations for Pen, Jet, and Related Injectors Submitted in Drug and Biological Product Applications

What You Need to Know? 👇

What are the key regulatory pathways for pen and jet injectors used with drugs and biologics?

Pen and jet injectors follow different regulatory pathways depending on their intended use. General use injectors are typically regulated as Class II devices under 510(k), while injectors intended for specific drugs/biologics are usually considered combination products regulated under NDA/BLA submissions.

What performance testing is required for injector dose accuracy validation?

Performance testing must demonstrate that the volume/weight of drug/biological product expelled matches the set dose. For multi-dose injectors, testing should verify accurate delivery for each successive dose and confirm that dose settings correlate with actual delivered volumes using the final approved dosage form.

How should biocompatibility testing be conducted for injector devices?

Biocompatibility testing should follow ISO-10993 guidance and consider all components contacting the patient, including fluid path materials. Testing must include appropriate extraction methods, animal models or cell lines, and endpoints like cytotoxicity, sensitization, and systemic toxicity based on contact type and duration.

What human factors considerations are critical for injector design and validation?

Human factors evaluation must consider the intended user population, environment of use, and physical limitations. Studies should validate users’ ability to read instructions, set up the injector, set proper doses, perform injections correctly, and dispose of materials safely using representative users.

What sterilization and sterility assurance requirements apply to injector systems?

Injectors must demonstrate sterility assurance with probability of non-sterile units not greater than 1 x 10-6. Fluid pathway components must be non-pyrogenic. For combination products, sterilization effects on both the injector and drug/biological product must be evaluated and justified.

What labeling requirements are essential for pen and jet injector products?

Labeling must include injector description, intended use, patient population, type-of-use specifications, contraindications, warnings, directions for use, assembly instructions, dose setting procedures, environmental conditions, disposal instructions, and troubleshooting guidance tailored to the end user and marketing configuration.

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What You Need to Do 👇

Recommended Actions

1. Determine the regulatory pathway based on intended use (510(k) vs NDA/BLA)
2. Conduct comprehensive design verification testing:
   • Performance testing
   • Biocompatibility
   • Stability/shelf-life
   • Human factors validation
3. Develop complete documentation package including:
   • Device description and specifications
   • Test protocols and reports
   • Risk analysis
   • Labeling
4. Consider early interactions with FDA through pre-submission meetings
5. Ensure sterilization validation and sterility assurance
6. Develop appropriate labeling for intended users
7. Validate manufacturing processes and quality systems
8. Address any drug-device compatibility issues
9. Consider need for clinical data based on risk assessment
10. Prepare marketing application according to appropriate format (510(k) or CTD)

Key Considerations

Clinical testing

• Human factors studies to evaluate user interactions and validate safe/effective use by intended population
• Evaluation of user-related risks
• Assessment of ability to read/understand instructions, setup injector, set proper dose, perform injection correctly
• Additional in-use testing may be needed for critical features

Non-clinical testing

• Performance testing for dose accuracy, depth and route of injection
• Testing under environmental conditions (temperature, storage, shipping, etc.)
• Functional testing (flow rate, injection time, reliability, safety features, etc.)
• Mechanical specifications testing (assembly force, actuation force, etc.)
• Shelf-life stability and expiration dating studies

Human Factors

• Comprehensive evaluation of all user-related risks
• Validation studies with representative users
• Assessment of ability to read/understand instructions, setup, dose setting, injection technique
• Consider user population characteristics (age, dexterity limitations, etc.)
• Consider environment of use conditions

Labeling

• Clear instructions for use appropriate for intended users
• Description of injector and indications
• Warnings, limitations, precautions
• Assembly and operation instructions
• Storage conditions and shelf-life
• Disposal instructions
• Patient labeling/medication guide as applicable

Biocompatibility

• Testing per ISO 10993-1 for patient-contacting components
• Evaluation of materials in fluid path
• Assessment of extractables/leachables
• Testing with actual drug/biological product

Safety

• Sterilization validation
• Assessment of cross-contamination risks for multi-patient devices
• Testing of safety features and protections
• Evaluation of sharps injury prevention features

Other considerations

• Materials compatibility with drug/biological products
• Container closure integrity
• Drug stability in device
• Manufacturing process controls
• Quality system requirements

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Relevant Guidances 🔗

• Applying Human Factors Engineering and Usability Engineering to Medical Devices
• Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
• Design Controls for Medical Device Manufacturers
• Reprocessing Instructions for Reusable Medical Devices and Non-Sterile Single-Use Devices - Development and Validation
• Human Factors Information Needed in Medical Device Marketing Submissions (Draft)

Related references and norms 📂

• ISO 7886-1: Sterile Hypodermic Syringes for Single Use - Part 1: Syringes for Manual Use
• ISO 10993-1: Biological Evaluation of Medical Devices - Part 1: Evaluation and Testing
• ISO 11608-1: Pen-Injectors for Medical Use – Part 1: Requirements and test methods
• ISO 11608-2: Pen-Injectors for Medical Use – Part 2: Needles – Requirements and test methods
• ISO 11608-3: Pen-Injectors for Medical Use – Part 3: Finished Cartridges – Requirements and test methods
• ISO 11608-4: Pen-Injectors for Medical Use – Part 4: Requirements and test methods for electronic and electromechanical pen-injectors
• ISO 21649: Needle-Free Injectors for Medical Use - Requirements and Test Methods
• ASTM D4169: Standard Practice for Performance Testing of Shipping Containers and Systems

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Original guidance

• Technical Considerations for Pen, Jet, and Related Injectors Submitted in Drug and Biological Product Applications
• HTML / PDF
• Issue date: 2013-06-07
• Last changed date: 2020-05-05
• Status: FINAL
• Official FDA topics: Medical Devices, Drugs, Combination Products, Biologics, Administrative / Procedural
• ReguVirta ID: 2068fa502397a2813489698f0a0da4f6