Use-Related Risk Analysis for Drug, Biological, and Combination Products: Determining Human Factors Study Needs (DRAFT)
This guidance provides recommendations on the purpose and content of a use-related risk analysis (URRA) for drugs, biological products, and combination products. It focuses on how URRA can be used along with other information to determine human factors (HF) data needs during product development and support marketing applications. The guidance primarily applies to drug and biologic-led combination products with device constituent parts, but may also apply to certain standalone drug and biological products.
This is a draft guidance. Not for implementation.
What You Need to Know? 👇
What is a Use-Related Risk Analysis (URRA) and why is it important for combination products?
A URRA is a risk analysis tool that identifies use-related hazards associated with medical product use and measures to reduce risks. It’s crucial for combination products as it helps characterize risks, supports product design decisions, and determines whether human factors validation studies are needed for marketing applications.
When should sponsors submit a URRA to FDA during product development?
Sponsors should initiate the URRA early in product development and submit it to support justifications for not conducting human factors validation studies or to inform HF study protocol design. It should be submitted under the IND for Agency review and updated throughout the product lifecycle.
What are the key components that must be included in a comprehensive URRA?
A URRA must include: a comprehensive list of all user tasks, potential use errors and associated harms, determination of critical versus noncritical tasks, risk control measures implemented in the user interface design, and evaluation methods used or planned to assess risk control effectiveness.
How does FDA determine whether human factors validation study results are required for marketing applications?
FDA evaluates each application individually, considering the URRA along with other information like comparative analyses. Factors include intended users, device characteristics, clinical impact of use errors, user familiarity with similar products, and the complexity of the use environment and tasks.
What types of risk controls should sponsors prioritize when mitigating use-related risks?
FDA expects sponsors to prioritize risk elimination or mitigation through device design rather than relying on labeling or training. The priority order is: inherently safe design and manufacture, protective measures in the product itself, and finally information for safety and training.
Can sponsors use comparative analyses with existing products to support their URRA submissions?
Yes, sponsors can conduct comparative analyses including labeling, task, and physical comparisons with similar marketed products. This helps identify differences in user interfaces and determine if the same risks apply, potentially supporting justifications for not submitting human factors validation studies.
What You Need to Do 👇
Recommended Actions
- Develop comprehensive URRA early in product development process
- Identify and document all user tasks and potential use errors
- Assess clinical impact and potential harms for each use error
- Categorize tasks as critical or non-critical
- Implement and document appropriate risk controls
- Define evaluation methods for risk controls
- Update URRA throughout product lifecycle
- Use URRA to determine need for HF validation study
- Consider comparative analyses when applicable
- Submit URRA with justification if proposing to not conduct HF validation study
- Use URRA to develop HF validation study protocol if needed
- Engage with FDA early to discuss HF development program
Key Considerations
Human Factors
- URRA should identify all tasks required for product use
- Tasks should be categorized as critical or non-critical
- Critical tasks are those which, if performed incorrectly or not at all, could cause harm
- URRA should be initiated early in development and updated throughout product lifecycle
- URRA should consider all intended uses, potential users, and likely use environments
Labelling
- Labeling should be considered as one aspect of risk control
- Information for safety through labels and labeling should be considered after design controls
- Labeling comparison may be needed when conducting comparative analyses
Safety
- Identify potential use errors and associated harms for each task
- Consider clinical impact of both one-time and repeated use errors
- Implement risk controls to reduce or eliminate risks
- Focus on eliminating risks through device design when feasible
- Consider risk controls in priority order: inherently safe design, protective measures, information for safety
Other considerations
- URRA can be used to justify not submitting HF validation study results
- URRA supports development of HF validation study protocols
- Consider comparative analyses when similar products exist
- Document evaluation methods for risk controls
- Consider use environment factors and user characteristics
Relevant Guidances 🔗
- Human Factors Information Needed in Medical Device Marketing Submissions (Draft)
- Applying Human Factors Engineering and Usability Engineering to Medical Devices
- List of Device Types That Require Human Factors Data in Premarket Submissions (Draft)
- Design Considerations for Medical Devices Intended for Home Use
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
Related references and norms 📂
- ISO 14971: Application of risk management to medical devices
- ISO TR 24971: Guidance on the application of ISO 14971
- ISO 13485: Medical devices – Quality management systems – Requirements for regulatory purposes