Application of Human Factors Engineering Principles for Combination Products

– Similar to the definition of critical tasks in the 2016 draft guidance [2], “a combination product critical task is a user task which, if performed incorrectly or not performed at all, would or could cause harm to the patient or user, where harm is defined to include compromised medical care.” Compromised medical care includes consideration of medication errors. This definition is different from the definition in Applying Human Factors and Usability Engineering to Medical Devices [1] due to the unique use-related risks associated with the combination product as a whole that do not exist for the device constituent parts alone or the drug alone. FDA is particularly interested in the assessment of tasks that directly: 

1. Impact dosing (e.g., overdose, underdose, or missed dose), including those that may lead to lack of treatment response.
2. Impact administration of the product (e.g., wrong site of administration, improper preparation of drug/biologic before administration) 
3. Have the potential to result in harm (e.g., physical injury, adverse events, events that may need patient monitoring to confirm no harm, or events that may lead to hospitalization)

For time-sensitive or time-urgent products (e.g., emergency-use autoinjector), most or all tasks are likely critical tasks. 

– Drug properties can affect users’ interactions and need to be considered when identifying, evaluating, and managing the use-related risks for the combination product. There may be use-related risks associated with the combination product as a whole that do not exist for the device alone or the drug alone. (e.g. high drug viscosity could increase injection delivery time)

– A comprehensive URRA (use-related risk analysis) should be used in the identification of combination product critical tasks. The Agency recommends to submit it as a separate risk analysis and not as a part of the full engineering risk analysis. When modifying combination products, URRA should include all aspects of the combination product to be modified and all elements of the combination product that may be affected by these modifications. 

– Consider using HF actual-use validation study (patients receiving actual medical care) for cases when simulated-use test methods are otherwise inadequate to evaluate users’ interactions with the final finished combination product. Note that HF actual-use validation studies should not be confused with other clinical studies with broader scopes.