FDA WARNING_LETTER - Pamela K. Den Besten, DDS, MS - October 15, 2024

This FDA Warning Letter, dated September 19, 2025, addresses Dr. Pamela K. Den Besten, DDS, MS, regarding objectionable conditions observed during an inspection conducted between September 16 and October 15, 2024. The inspection reviewed Dr. Den Besten"s conduct as sponsor-investigator for Protocol 15-18297, "Pilot Study: Oral Microbiome and Dental Plaque Control with Livionex® Dental Gel in Children Undergoing Hematopoietic Stem Cell Transplantation (HSCT)."

The primary violation cited was Dr. Den Besten"s failure to submit an Investigational New Drug (IND) application and have it in effect for the clinical investigation of Livionex® Dental Gel. The study, which enrolled 43 subjects between 2016 and 2020, investigated Livionex"s efficacy in mitigating or treating gingivitis and dental caries, thus classifying it as a "drug" under section 201(g)(1) of the Federal Food, Drug, and Cosmetic Act. Consequently, it required an IND per 21 CFR Part 312. Dr. Den Besten incorrectly relied on an IND exemption, asserting that Livionex was a lawfully marketed over-the-counter product, which the FDA refuted as Livionex is not an approved drug and does not contain active ingredients from any OTC monograph.

While Dr. Den Besten acknowledged the findings and outlined corrective actions, including training and internal procedure reviews, the FDA deemed her November 5, 2024, response inadequate. The letter implies a need for further comprehensive and adequate corrective and preventive actions to ensure full compliance with FDA regulations governing clinical investigations and human subject protection.