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Essential Drug Delivery Outputs for Drug Delivery Devices and Combination Products (DRAFT)

This guidance addresses key aspects of drug delivery performance information for devices and combination products with device constituent parts intended for delivery of human drugs and biological products. It focuses on essential drug delivery outputs (EDDOs) - the device design outputs necessary to ensure proper drug delivery function, including product preparation, initiation, progression, and completion of dose delivery.

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By ReguVirta
4 min read

This is a draft guidance. Not for implementation.

What You Need to Know? 👇

What are Essential Drug Delivery Outputs (EDDOs) and how do they differ from other design outputs?

EDDOs are device design outputs necessary to ensure delivery of the intended drug dose to the intended delivery site. They are system-level outputs that are device-dependent and essential for proper drug delivery function, unlike component-level outputs or user-dependent functions.

When should EDDO verification and validation testing be completed during product development?

EDDO verification should be completed prior to initiating clinical studies or commercial distribution. Design validation should occur using production units under actual or simulated use conditions, with comprehensive validation data required before pivotal clinical studies for marketing applications.

What preconditioning requirements apply to EDDO verification testing?

Preconditioning should simulate real-world stressors including storage conditions (temperature, humidity), shipping conditions (vibration, shock), and use-related conditions. Sequential preconditioning is generally expected for emergency-use injectors, and the sequence should reflect actual product lifecycle exposures.

How do EDDO requirements differ between original marketing applications and post-market changes?

Original applications require complete EDDO identification, verification, and validation with control strategies. Post-market changes require impact assessment of modifications on existing EDDOs, verification of unchanged specifications, and validation of new specifications with updated control strategies as needed.

Control strategies should be risk-based, combining upstream controls (in-process controls, process parameters, incoming materials) and downstream controls (lot release testing). Higher-risk products typically require multiple control types, while lower-risk products may rely primarily on downstream controls.

How should applicants engage with FDA regarding EDDO development and validation strategies?

Applicants should seek FDA feedback through formal meetings or communications during development, providing clear product descriptions, specific EDDO questions, and proposed control strategies. Early engagement helps ensure appropriate EDDO identification and validation approaches before pivotal studies.

What You Need to Do 👇

  1. Identify EDDOs early in development using the filtering process outlined in the guidance
  2. Develop verification and validation plans for EDDOs considering:
    • Preconditioning requirements
    • Stability/shelf-life testing needs
    • Appropriate sampling plans
    • Clinical validation where applicable
  3. Establish risk-based control strategy for EDDOs including:
    • Upstream controls (process parameters, incoming materials)
    • Downstream controls (release testing)
    • Documentation requirements
  4. Submit appropriate EDDO information in regulatory applications:
    • Device description and engineering documentation
    • Verification and validation data
    • Control strategy details
    • Risk analysis
  5. Evaluate impact of post-approval changes on EDDOs and update control strategy as needed
  6. Engage with FDA early regarding proposed EDDOs and control strategy through formal meetings
  7. Maintain documentation of EDDO identification, verification, validation and control throughout product lifecycle

Key Considerations

Clinical testing

  • Clinical studies may be used to validate EDDOs
  • Clinical protocols should include endpoints relevant to device performance
  • Safety endpoints should capture device failures and malfunctions

Non-clinical testing

  • Design verification testing after appropriate preconditioning
  • Shelf-life and stability testing for EDDOs that may change over time
  • Risk-based sampling plans considering indication, population, drug, use context
  • Testing should evaluate impact of storage, shipping, and use conditions

Labelling

  • Instructions for use should be considered when identifying EDDOs
  • Labeling changes that could impact EDDOs require evaluation

Safety

  • EDDOs necessary for patient safety should be verified and validated before clinical studies
  • Risk analysis should include EDDO-related risks

Other considerations

  • Control strategy should be risk-based with appropriate upstream and downstream controls
  • Changes to product design or manufacturing require evaluation of impact on EDDOs
  • Documentation of EDDO identification, verification, validation and control is required
  • Early interaction with FDA recommended regarding proposed EDDOs and control strategy

Relevant Guidances 🔗

Related references and norms 📂

  • ANSI/AAMI HE 75:2009 (R2018): Human factors engineering – Design of medical devices
  • ISO 13485:2016: Medical devices – Quality management systems – Requirements for regulatory purposes
  • USP <601>: Aerosols, sprays, and powders
  • USP <1601>: Nebulizer products

Original guidance

  • Essential Drug Delivery Outputs for Drug Delivery Devices and Combination Products
  • HTML / PDF
  • Issue date: 2024-06-28
  • Last changed date: 2024-07-08
  • Status: DRAFT
  • Official FDA topics: Medical Devices, Pediatric Product Development, Drugs, Combination Products, Biologics
  • ReguVirta ID: 097f6205ec579625fa0df6707c642b83
FDA guidance, Draft
Medical Devices Pediatric Product Development Drugs Combination Products Biologics
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