Chromatographically Contaminated Cosmeceutical

I direct the analytical R&D group of a mid-sized cosmetics manufacturer. We mostly market our product to larger brands who package and label it according to license and they hold the filings for any drug-related cosmetics involved. We also have a few final market products with several in development. One of these is a topical moisturizing cream with a proprietary astringent agent, nearing submission of a regulatory filing. The maximum daily application dose of our drug is within the range 10mg - 2g, so the ID threshold for an unknown impurity is 0.2%. The situation is that on accelerated stability, we have detected an unidentified impurity above the 0.2% threshold that is most likely a product of the astringent reacting with one of the excipients. The impurity appeared at one month at 40°C/75%RH in the first of three batches on stability, thus it will likely show up later at long-term conditions.

Our commercial QA management is insisting that we ID this impurity along with toxicological assessments and is even implying that we should synthesize the impurity to aid in tox studies and set a stability specification. They cite ICH Q1A and other pharmaceutical guidances, but we’re looking at a one-to-two-year delay to market if we hold off filing pending these analytical analyses. Since this is a topical cosmetic, I’m pushing back that such stringent requirements do not actually apply to us. The product is well within our potency specifications and whatever is going on chemically, clearly it does not impact product efficacy and has no impact on pH or physical properties, including appearance and viscosity.

Of these three possible filing routes, which would you recommend, and why? Alternatively, if you have another strategy, please share it.

Three possible filing strategies:

1. Delay the filing as much as two years to proceed with full ID, synthesis and tox studies for this impurity and include a stability specification for it in the NDA. 2. Delay the filing for 6 months to gather 12-months of long-term stability data hopefully showing no detectable impurity or below the ID threshold, and full product efficacy. 3. File per current schedule including all the data, justifying that it meets current specs and does not impact product efficacy.