At the Generic Drug Forum virtual SBIA event that is still ongoing, Andrew J. Fine, PharmD, BCPS, Senior Advisor, Division of Clinical Review, Office of Safety & Clinical Evaluation, Office of Generic Drugs, provided a look at the type of information that needs to accompany a complex product (particularly a drug device combination) to establish sameness for the purposes of approval of a generic version of such an RLD.

We have all heard that for a generic drug device combination product, “FDA considers whether end-users can use the generic combination product when it is substituted for the reference listed drug (RLD) without the intervention of the healthcare professional and/or without additional training prior to the use of the generic combination product.”  This assessment needs to be accomplished to establish therapeutic equivalence (TE), which is necessary for a generic product to be approved and substitutable.  The FDA has also noted that the generic and RLD do not have to be “identical” in every aspect as long as the differences do not preclude ANDA approval.

Dr. Fine’s presentation covered, in considerable detail, evaluation of external critical design attributes that “affect how users perform a critical task that is necessary in order to use or administer the drug product” and noted that “critical tasks may be considered 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 care.”  All of the evaluations lead back to the labeling of the RLD and the differences identified from the RLD product.

The evaluation takes into consideration the context of urgency of use (i.e., emergency, life‑threating events), frequency of use (single use or repeated use), end user (patient, caregiver, or healthcare provider), and environment of use (clinic, hospital, school), as well as the target patient population and their ability to utilize the product correctly (such as dexterity issues or, for a product like naloxone or glucagon, when the patient may be unconscious and someone else must administer the product).

The presentation also went on to detail issues with other device considerations such as accuracy of dosing cups and syringes, proper orientation of dose markings on the device, appropriate contrast between the drug and color of the markings, removal of trailing zeros to help prevent dose errors, and ensuring that there are no extraneous markings on the device that could confuse the patient.

Overall, it was quite an interesting perspective towards establishing TE for certain product classes with lots of good advice on avoiding pitfalls along the way in support of an acceptable and approvable ANDA submission.