Use-Related Risk Analysis: Considering The FDA Guidance On URRA

By Fran DeGrazio, executive editor, Drug Delivery Leader

2024 was an exciting year for newly released FDA guidances. Among those regulatory documents garnering significant attention was the Purpose and Content of Use-Related Risk Analyses for Drugs, Biological Products, and Combination Products, released in July. This draft guidance on conducting a URRA (Use-Related Risk Analysis) was especially welcomed and needed, as deficiencies in URRAs have been reported as a leading cause of delays with FDA submissions.
During product development, a URRA is a tool used to identify hazards related to product use and to include specific focus on those hazards in documentation provided to the FDA as part of the regulatory review and approval process.
In November 2024, I had the pleasure of moderating a Drug Delivery Leader Live! event, Human Factors Risk Analysis: Leveraging URRA And uFMEA Tools, designed to raise awareness and understanding of the FDA URRA guidance. Joining me and Drug Delivery Leader Chief Editor and event co-host, Tom von Gunden, were SMEs (subject matter experts) Shannon Hoste, Chief Scientific Officer at Pathway for Patient Health, and Natalie Abts, who leads human factors work at Genentech.
Key topics from the event intended to help biopharma organizations in determining when and how to implement a URRA included the following:
- URRA and uFMEA comparison
- URRA documentation
- URRA and IFU relationship
URRA And uFMEA: Two Tools To Leverage
In addition to the URRA, there is an additional tool also commonly used in conducting risk analysis for new products, the User Failure Modes & Effects Analysis, or uFMEA. A uFMEA is typically utilized by engineers during development activities. A developer would identify the product usage steps and identify which tasks are most likely to result in errors. These areas would have the highest priority for mitigating risk by redesign, labeling, or visual prompts, as examples. Given the thoroughness of the detail often documented in a uFMEA, the information gleaned from it may helpfully form the basis for the URRA, if used selectively and judiciously (more on that below). In the Live! event, panelist Natalie and Shannon offered illustrations and suggestions about using a uFMEA, including in conjunction with or as an input to a URRA.
URRA Documentation: Less May Be More
A significant point of clarification in the FDA’s guidance is the intent, type, and amount of information the agency is looking for in URRA documentation. The guidance focuses on clarifying what it will want to see in terms of the work organizations have done to identify user tasks, potential use errors, and other harms associated with users. In the Live! event, we cautioned the audience that providing too much information – for example, simply inserting most or all of the voluminous documentation about risk gleaned from a previously or contemporaneously conducted uFMEA – could be, at best, unnecessary and, at worst, a cause of confusion during the review process.
The FDA’s URRA guidance helpfully provides agency perspective and illustrative standardization around the risk documentation desired or expected in a regulatory application. Aspects clarified by the guidance include identifying critical tasks and the associated risk control measures required to prevent or reduce errors.
Another documentation topic that we discussed in the November 2024 Live! event on URRA was validation of issues identified during risk analyses. Shannon Hoste commented on the impact of validation on regulatory strategy. Natalie Abts offered ways to justify leveraging information already available rather than building all the data from scratch by generating new validation protocols or executing additional validations just for URRA purposes.
URRA And IFU: Effective Sequencing
During the Drug Delivery Leader Live! event we polled the audience about when they start to assemble their IFU (Instructions for Use) and in what, if any, relation to the generation of a URRA. The poll results confirmed that a significant percentage of the audience completes the IFU and the URRA at the same time. While not necessarily a ‘wrong’ practice, working on the IFU and the URRA simultaneously may create a missed opportunity. If sequenced – URRA first, followed by IFU – the insights gained from risk analysis might drive development up to and including the IFU generation process.
Panelist Shannon Hoste offered some compelling rationale for starting URRA work early in product development. Mapping the tasks and risks early can help provide guidance not just about the IFU but potentially to other areas such as drug formulation or clinical studies.
In summary, the FDA URRA guidance reinforces several key issues:
- Purpose and content of a URRA
- Clarifying how the URRA plays a role in determining the human factors data needed
- Identifying product use tasks that could lead to harm due to error
- Estimating and understanding the potential risk of a product
In all instances, the FDA is looking for clear, targeted data and consolidated scientific information that meets their needs for URRA documentation during regulatory review. Frankly, while not perfect, this draft guidance does provide useful clarity on many of these considerations.