Finding External Critical Design Attributes
In January, 2017, FDA introduced a draft guidance “Comparative Analyses and Related Comparative Use Human Factors Studies for a Drug-Device Combination Product Submitted in an ANDA: Draft Guidance for Industry” (ucm536959), to help potential applicants who plan to develop and submit an abbreviated new drug application (ANDA). In a nutshell, the guidance provides recommendations and FDA views on the comparative user interface analysis of the generic combination product and the reference listed drug (RLD).
Regarding the user interface analysis, the draft guidance strongly suggests to employ the Threshold Analysis in order to detect, analyse and evaluate the differences between the generic combination product and RLD. The Threshold Analysis can be seen as relatively new Human Factors analysis and FDA has given their thoughts on what they would expect the sponsor to do to complete the analysis.
Among the other things, FDA recommends to examine the external critical design attributes. Knowing the external critical design attributes will be crucial when evaluating differences between the two products. This leads to the question – what is an external critical design attribute (CDA)? The FDA draft guidance states that external critical design attributes are “features that directly affect how users perform a critical task that is necessary in order to use or administer the drug product”.
In order to identify the critical design attributes, FDA guidance suggests to examine the overall external operating principles of the delivery device constituent part. This would require the evaluation of all the tasks that the user needs to perform to prepare and administer the product. FDA does give some indication of what a CDA is, stating…“Among those tasks, certain ones will be identified as critical to the use of the product, and the external critical design attributes of the product would be those features that end-users rely on to safely and effectively perform those identified critical tasks.”
Therefore, the activities that are performed in following order should help to detect critical external design attributes:
- Analyse overall external operating principle
- Detect critical tasks
- Detect external CDA
To illustrate this, one task to use an auto injector could be looked at. To administer the drug, a critical task would be to press an actuator button. In this task the user interface elements that user will rely on would be a visual appearance of the actuator button, a size of the actuator button and a shape of the actuator button. It also might be a diameter of a barrel of the auto injector that user is holding to perform the task. There also could be an audible click heard by the user during this task. Therefore, all these elements could be seen as CDA. Once the CDA have been detected they can further help to evaluate the differences between the RLD and generic combination product when completing all the Threshold Analyses.
It should be pointed out that as the sponsor has to detect external CDA for both devices in order to compare them, the critical tasks also have to be identified for both devices. In addition, more likely the sponsor will not have an access to the RLD risk assessment that sets criticality of the tasks, therefore, when detecting the critical tasks and analysing the external operating principle for the competitor’s product, it should be kept in mind that to some extent the sponsor will have to make assumptions and the analysis will be their take on the matter. FDA guidance Human Factors Studies and Related Clinical Study Considerations in Combination Product Design and Development could help the sponsor to understand FDA current thinking on critical tasks. Sponsor also may consider to involve an external consultant to assist them, especially when analysing and comparing the competitor’s product to their own combination product and evaluating the differences.