10/08/2025
Photo by Supliful - Supplements On Demand on Unsplash
On April 30th, 2025, the U.S. Food and Drug Administration (FDA) issued a warning letter and Form FDA 483 to the sponsor of a clinical investigation as the results of a Bioresearch Monitoring Program (BIMO) inspection. The clinical investigation was for an investigational product (IP) that the sponsor claims was to help individuals with sleeping disorders. 40 participants were enrolled in the study and took the IP without the sponsor submitting an Investigational New Drug (IND) application as required per 21 CFR 312 and FD&C Act. As a sponsor, submitting and having in effect an IND is required for the clinical investigation of any investigational drug.
“Drug” is the key term in this scenario because in their response to the FDA, the sponsor company stated that the formulation, labeling, marketing, and advertising of the article in question is that of a dietary supplement, not a drug. Under the FD&C Act as well as U.S Code, a drug is defined as “articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease” and “articles (other than food) intended to affect the structure or any function of the body of man or other animals”. The sponsor’s response goes on to say that whether or not their article has any effect on individuals with sleep disorders is not evidence of it being a drug as defined by the U.S Code Title 21 section 321(g). Furthermore, they stated that even if they are determining the effect of a dietary supplement on a person with a particular condition, this does not mean that the intended use of the supplement is to treat the condition. The sponsor’s authorized representative also added that at no point was the article intended to treat, cure, mitigate, or diagnose a disease.
In both definitions, the intentionality of the article (and in this case, the clinical investigation of the article) is what determines if it is a drug. To evaluate the investigation’s intent, the BIMO investigators analyzed the trial’s protocol. The primary objective of the study according to the protocol was to investigate the effect of the article on sleep parameters in individuals with insomnia. These sleep parameters measured the variability and quality of sleep and were identified as the studies efficacy endpoints. The investigators determined that the intentions of the article, as it was described in the protocol, was to treat and mitigate insomnia (insomnia being the disease/condition) and thus concluded that the trial did require an IND.
Despite the FDA Form 483, the sponsor’s written response claimed that since they were not in the business of performing clinical studies, they were not at risk of future violation. This response did not ease any of the concerns the FDA had with both the company and the safety and welfare of the enrolled participants. The warning letter concludes with a requirement for the sponsor to provide in writing preventative actions the company will take to ensure similar violations do not happen again, or be met with regulatory action.
The full warning letter is available on the FDA website. If you or your company have received a notification about an upcoming BIMO inspection, it is always best to be proactive and ready for the inspection even if it does not seem warranted. Clinical Pathways offers a wide variety of services and training that helps prepare for these inspections and teaches best practices for hosting and following up with the inspectors especially if a Form 483 is issued. For a full list of courses and services please visit our online store.
-The Clinical Pathways Team
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