Like with all medical devices, the application of human factors principles is essential for the development of safe and effective combination products. On September 7, 2023, the FDA released “Application of Human Factors Engineering Principles for Combination Products: Questions and Answers,” a guidance document containing 15 questions and answers on the application of human factors engineering principles to the development of combination products (https://www.fda.gov/media/171855/download).
While this document primarily streamlines topics that have been covered to some extent in a variety of other published guidance documents, our objective is to help you stay informed about the latest advancements in our industry.
So, if you’re developing a combination product, or just interested in the contents of this new guidance document, we’ve simplified it down to three main topics and highlight what we consider to be the key takeaways in each. The specific question number is referenced in orange.
1. FDA’s relevant definitions
- The document starts off by defining combination products, which are medical devices combined with a drug or biological product. These products have their own separate regulatory requirements as drugs, devices, or biological products, but they also fall under specialized regulatory requirements when they are combined.
- On that note, the document defines a final finished combination product as the product intended for market and submitted in the marketing application. This includes the user interface for the combination product – packaging, labels, and training, if applicable. (Q-4)
- A combination product critical task is a user task that, if done wrong or not done at all, could harm the patient or user and compromise medical care. It accounts for unique use-related risks of the combination of the drug or biologic product and device. The definition of a combination product critical task differs from that of a device-only critical task in the level of harm – with a stand-alone device, only tasks with the potential for serious harm are considered critical. (Q-5)
2. The importance of a Use Related Risk Analysis
- Like all medical devices, combination products are subject to design validation and use related risk analysis (URRA) where appropriate.
- A URRA is a subset of the overall engineering risk analysis, with focus on intended use and risk of foreseeable misuse. (Q-7)
- The URRA should consider all potential risks associated with the combination product as a whole, not just the device, drug, or biological product alone.
- For example, for a combination product like a medication injection device, a drug property like viscosity could increase injection delivery time increasing the risk of potential under-dosing. (Q-2)
- A URRA should be conducted before beginning a clinical study to identify any potential risk of harm to the participants due to incorrect use of the combination product during the study. This document makes clear that the FDA may request the URRA if there are any safety concerns. If the URRA shows any “unacceptable risks,” a human factors validation study may be required, and a draft of the study protocol should be submitted for feedback before proceeding. (Q-11)
- When planning a combination product design change, consider all potential effects on the URRA. Depending on how the changes affect use, an additional human factors validation study may be necessary, focusing at the very least, on the combination product critical tasks impacted by the modification. (Q-13)
3. FDA’s Human Factors considerations at different development phases
- The FDA reviews formative human factors evaluations as part of a draft protocol submission, the human factors report in the marketing application, or both, to better understand the development of the user interface design of the combination product. (Q-10)
- The FDA will review draft human factors validation study protocols within the lead center’s established time frame. If draft labeling is included, the labeling leads in each center will conduct a pre-study review to prevent post-study revisions. (Q-14)
- The human factors validation study is conducted after finalizing the user interface design to ensure the safe and effective use of the product by its intended users in the expected environment. In some cases, if the final finished combination product is not ready, a sufficiently representative test product may be used if justified. (Q-12)
- If training is included in the user interface design, it should be validated, including the training of trainers. Both trained and untrained users should be tested if training is optional or inconsistent, with the possibility of testing only untrained users in certain cases. (Q-8)
- Human factors actual-use validation studies are conducted when simulated-use test methods are not sufficient to evaluate user interactions with the final finished combination product. These studies assess the user interface of the device and are distinct from actual use or clinical home use studies that focus on clinical safety and effectiveness, where the user interface is not observed by a human factors evaluator. (Q-9)
Bonus: Further FDA Guidance
- “Safety Considerations for Product Design to Minimize Medication Errors“ (https://www.fda.gov/media/84903/download) provides guidance for medication error considerations in designing combination products (Q-1)
- The general definitions in “Applying Human Factors and Usability Engineering to Medical Devices” (https://www.fda.gov/media/80481/download) apply to the entire combination product, not just the device. There are only two definitions specific to combination products: the final finished combination product and combination product critical task (both described earlier in the video). (Q-3)
- To obtain information from the FDA on a specific combination product’s HF program, it is recommended to submit documents for review and requests for meetings to the lead center for the application type, indicating that the discussion is for a combination product and requesting participation from all relevant centers and the Office of Combination Products (OCP). (Q-15)
- Once the HF report is submitted, the goal of the FDA’s review of the HF validation study is to determine if the user interface design has effectively reduced use-related risks. (Q-6)
Contact us to learn more about FDA’s guidances, human factors, and how we can assist your human factors needs.
