Specifically, each threshold analysis finding belongs to one of three categories:
| No design difference | A given user interface feature, function or characteristic is the same between the proposed generic and RLD products. The term “user interface” refers to all components of the combination product with which a user interacts. |
| Minor design difference | A user interface difference does not impact an external critical design attribute and should not affect the performance of a combination product-critical task. |
| Other design differences | A user interface difference that may impact an external critical design attribute involving drug administration. |
When evaluating and categorizing the differences, it is important to keep the product user in mind. For example, suppose that the RLD emits an audible “click” once the dose has been delivered, but the proposed product emits an audible “click” when dose delivery starts. Will the difference in the audible signal timing confuse the user? Might they mistake the click made by the proposed product as the signal that the dose has been delivered and, therefore, prematurely remove the inhaler from their mouth before receiving a full dose?
When categorizing design differences as “minor” versus “other” during threshold analyses, It is essential first to determine if a difference is related to a critical task for a combination product. A 2022 FDA guidance defines combination product critical tasks as “user tasks that, 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.”
Because combination critical tasks are device and intended use subjective, an MDI requiring priming and breath-dose coordination will have different combination product critical tasks compared to a DPI requiring dose loading by placing and puncturing the capsule.
Suppose you identified a difference between the caps of the RLD and generic inhalers where the cap is a product feature not associated with a combination product critical task. In that case, this likely constitutes a “minor difference.” Another example could be the difference in the manufacturer’s name placement on the generic inhaler versus the RLD inhaler’s outer package.
