06/23/2025

On June 5, 2025, the US Food and Drug Administration (FDA) issued a warning letter and FDA Form 483 to an investigator as a result of objectional conditions observed during a Bioresearch Monitoring Program (BIMO) inspection. According to the letter, the investigator did not adhere to the applicable statutory requirements of Title 21 CFR part 312.60 which states: “An investigator is responsible for ensuring that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulations”.

The investigational plan for this study required that participants meet all eligibility criteria during screening before being enrolled in the study and given investigational treatment. However, in two instances, the protocol exclusion criteria that participants cannot have any risk factors for progression to severe disease was neglected. In this case, the risk factor was obesity, defined as a body mass index of ≥ 30 kg/m2 in participants 18+ years old. Two participants, despite meeting the exclusion criterion were both enrolled and given the investigational product (IP) on the same day as screening. Eligibility criteria are put in place in order to protect prospective participants that may experience adverse reactions to the novel treatment whether it be due to their age, medical history, or other factors that have either have not been tested or have shown negative effects in previous studies. By ignoring these criteria, these two participant’s safety and wellbeing were put at risk regardless of how they reacted to the IP.

In their response to the warning letter, the investigator stated that a corrective and preventative action (CAPA) plan was put in place and that going forward there will be more oversight, collaboration, and training for the sponsor, CRO, and study team to ensure they are all aware and competent in all eligibility criteria. This response however was deemed inadequate as it did not include any corrective actions that would resolve the objectionable condition of protocol deviations. The warning letter emphasized that as the principal investigator (PI) it is their responsibility to ensure the study be conducted in adherence to the protocol and study plan in order to protect the rights, safety, and well-being of all study participants. It is the PI’s responsibility to review and confirm that each prospective participant has met all eligibility criteria before they are enrolled and before receiving the IP. The study team or CRO may have overlooked that the participant was ineligible; however, the PI has an obligation to review all relevant documentation and identify such mistakes before enrolling and administering the IP to participants. The full warning letter is available on the FDA’s website.

Even a single observation from a BIMO inspection can potentially halt the development of a new therapeutic product if not properly dealt with, as well as tarnish the reputability of the stakeholders involved. Whether you or your company have been notified of an upcoming BIMO inspection or not, it is best to be prepared for when the FDA eventually does send notification. Clinical Pathways offers a wide variety of consulting services to help in this preparation including virtual or in-person BIMO inspection readiness and CAPA planning. For a full list of our services please visit our website and check out our online store and course catalog, and while you are there sign up for our free blog and newsletter to stay up-to-date on clinical trial related news such as this.

-The Clinical Pathways Team

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