10/30/2025
Photo by Christina Radevich on Unsplash
On March 25, 2025 the U.S. Food and Drug Administration (FDA) issued a warning letter to the sponsor-investigator of a study due to objectionable conditions observed during a Bioresearch Monitoring (BIMO) Program inspection. Sponsor-investigator warning letters are quite common as it requires taking on the responsibilities of both roles and often are academic or investigator-initiated. These usually smaller studies are often limited in study personnel and funding compared to larger sponsor companies which can result in a lack of adequate oversight, monitoring and data quality. Furthermore, there may be misunderstandings about the regulatory requirements that are usually delegated to the sponsor, this is common especially in first time investigator-initialed trials. The sponsor-investigator’s written response to the FDA Form 483 were deemed inadequate therefore the FDA issued a warning letter stating that the sponsor-investigator was noncompliant with multiple regulations within 21 CFR part 312 (Investigational New Drug Application).
1. You failed to ensure that an investigation was conducted according to the signed investigator statement, the investigational plan, and applicable regulations. 21 CFR § 312.60.
This is one of the more commonly cited violations in warning letters as it can be applied to many areas of study conduct such as participant eligibility, investigational product (IP) management, and institutional review board (IRB) reporting (examples of § 312.60 in previously covered warning letters: 10/22/2024, 06/23/2025, 07/29/2025). In this instance, 3 separate issues were all documented under this violation:
a. Participant eligibility criteria: A study participant was dosed with IP prior to completing protocol-specified laboratory and imaging assessments that would determine eligibility.
b. IRB Reporting: Per the protocol, all adverse events (AE) were to be recorded immediately in the source documents and cases of serious AEs (SAE) were to be reported to the IRB. In 2 cases of SAEs, there was no reporting to the IRB.
c. Data and Safety Monitoring Board (DSMB) Reporting: The protocol stated that all safety/adverse event data was required to be sent to the DSMB for review. However, when a participant’s condition began to deteriorate following administration of IP and underwent a surgical procedure as treatment, there was no documented reporting of the SAE to the DSMB.
2. You failed to ensure proper monitoring of the investigation(s) and to ensure that the investigation(s) were conducted in accordance with the general investigational plan and protocols contained in the IND. 21 CFR § 312.50.
Similar to the previous observation, the protocol stated that all safety events would be sent to an Independent Medical Monitor. None of the AEs or SAEs were sent to the Medical Monitor.
3. You failed to retain records and reports as required for 2 years after a marketing application is approved for the drug; or, if an application is not approved for the drug, until 2 years after shipment and delivery of the drug for investigational use is discontinued and FDA has been so notified 21 CFR § 312.57(c).
During the time of the inspection, complete and contemporaneous source records were not made available to the inspectors. In the sponsor-investigator’s response, they acknowledged that source records and reports were not retained for the 2-year minimum which is why it was not available during the inspection. They also claim it was due to the IP supplying company closing its Electronic Data Capture (EDC) system but did not provide any preventative actions on how they would secure access to EDC systems in the future. However, the FDA was able to access the supplier’s EDC files and noted that there was also a lack of source data on AEs. While this may have been an issue that started with the supplier, ultimately the responsibility falls on the sponsor-investigator for having limited oversight of their vendor.
The full warning letter including all of the sponsor’s responses and proposed Corrective and Preventative Action plans (CAPA) can be found on the FDA website. With 3 separate violations cited and further issues under each, this warning letter shows examples of poor trial conduct on all levels from data management to IP administration. Even if addressed properly, the violations may leave the FDA concerned for the rights safety and welfare of all trial participants in this study and any future research the sponsor-investigator may conduct.
As mentioned above, taking on the roles and responsibilities of both sponsor and investigator can be overwhelming even for individuals with experience in the field. In cases such as this, it is essential to have adequate oversight in every area of trial conduct and to be proactive in identify any gaps or deficiencies and implementing proper CAPAs before the FDA arrives. This is where Clinical Pathways can be of assistance in order to get an independent evaluation of a trial and identify areas that may require attention or improvement to stay one step ahead of regulators. We offer a wide range of educational and consulting services that prepare sites and study personnel for inspections and offer guidance throughout every step of the BIMO inspection process. For more information and a list of all of our services and courses please visit our website, and while you are there make sure to sign up for our free newsletter and blog to stay up to date on clinical trial related news such as this.
-The Clinical Pathways Team
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