In January, 2017 the US FDA published a draft guidance, Comparative Analyses and Related Comparative Use Human Factors Studies for a Drug-Device Combination Product Submitted in an ANDA: Draft Guidance for Industry.
Since then a number of friends, colleagues, and clients have asked me about my thoughts. It takes a while to read through, but I found the draft guidance helpful in clarifying expectations for companies trying to bring to market generic combination products using the abbreviated new drug application (ANDA) pathway.
Some key take-aways:
Combination products within the scope of this guidance are those with a drug primary mode of action, so CDER has primary jurisdiction and will coordinate with CDRH as appropriate.
During the design process, manufacturers should try to minimize differences in the user interface for their proposed device compared to the user interface for the reference listed drug (RLD).
If there are any differences, the Agency strongly recommends that the manufacturer conduct three types of ‘threshold analyses’:
Comparative task analysis
Physical comparison of the delivery devices
There are two possible outcomes of these threshold analyses:
No design differences (FDA likely won’t require additional data); or
Differences in design – which can be ‘minor’ (do not affect an external critical design attribute), or ‘other’ (may impact an external critical design attribute).
If there are differences impacting critical design attributes (those that directly affect how users perform critical tasks necessary to use or administer the drug product), then the Agency is likely to request additional data to show that the differences do not preclude submitting an ANDA.
When needed, the additional data should be gathered by conducting comparative human factors studies – and these must be carefully designed and statistically valid.
These comparative HF studies are in addition to the normal human factors validation studies typically required.
My final take-away was in footnote 12, which states: “…FDA does not necessarily expect for approval that a generic combination product can be used according to the RLD labeling per se, but rather it is critical that the generic combination product can be substituted for the RLD without additional physician intervention and/or retraining prior to use.”
This makes sense, given that in common real-world scenarios, patients who have been using a device for some time may go to the pharmacy to pick up their prescription and be given a new generic equivalent. These patients should be able to take the new device home and use it without any retraining. (It’s important to note, by the way, that Appendix A on conducting comparative human factors studies of this draft guidance is nearly identical to the corresponding Appendix A of FDA’s other recently-released draft guidance, Considerations in Demonstrating Interchangeability with a Reference Product: Guidance for Industry, but with some key differences since demonstrating equivalence and demonstrating interchangeability are different.
FDA will be accepting comments and suggestions on these draft guidance documents until mid-March, 2017.
photo credit: Dave Kennard