In a Federal Register notice (here) that will publish on Monday, August 30th, the FDA announced that it “is withdrawing approval of the abbreviated new drug application (ANDA) for solifenacin succinate tablets, 5 milligrams (mg) and 10 mg, held by Breckenridge Pharmaceutical, Inc.”  Breckenridge waived its opportunity for hearing on the proposed withdrawal.

What makes this instance so unusual are the circumstances surrounding the reason for this action.  And to be honest, this is the first time that I can remember that these circumstances formed the basis for a withdrawal.  Okay, now let’s dispense with the suspense and get to the meat of the issue.  “On January 23, 2020, Breckenridge issued a field alert report that solifenacin succinate tablets, 5 mg and 10 mg, may convert to solifenacin tartrate tablets during manufacturing due to an interaction between solifenacin succinate and tartartic acid, which is an inactive ingredient in this drug product’s formulation.”  Apparently, the conversion took place in situ over time and, when the firm noticed this fact, they issued the field alert referenced above and, a day later, issued a class II recall of the product.

In discussions with the firm, the FDA indicated that since there was a partial conversion of the active ingredient to a different salt, the product “contained” a different active ingredient than the reference listed drug (RLD) and, thus, the product was no longer the “same as” the RLD and was considered misbranded.

Now here is the watch-out!  The inclusion of the inactive ingredient tartaric acid in the product appears to have been the culprit in this story.  Many people consider inactive ingredients inert but, as this case proves, that is not the case.  The FDA’s attention to the selection of inactive ingredients for use in a formulation has intensified over the years to ensure that they are appropriate for and will not adversely impact the product.  Here is a case where the product was approved on May 20, 2019 and the issue was not found until just before the field alert was submitted eight months post-approval.

There are fifteen other approved manufacturers of generic solifenacin succinate tablets; I assume that the OGD is taking or has taken a hard look at the formulations of those other products!