10/22/2024
Photo by D koi on Unsplash
On August 20th, 2024 the US Food and Drug Administration (FDA) issued a warning letter as a result of an FDA Bioresearch Monitoring (BIMO) Program inspection. The inspection observation was that improper dosing instructions were given to a pediatric patient. Per 21 CFR 312.60, the investigator is responsible for ensuring the study is conducted according to the protocol. According to the protocol, subjects between the ages 12-18 were to receive a dose that did not exceed 12.5 mg per day of investigational product (IP). However, a 15-year-old subject, who was supposed to receive 1.2 mL of IP (~12mg) daily, was given a bottle of the IP with the dosing instructions to take 12.0 mL (120mg) every day, which they did for seven days. The subject took ten times the maximum daily dose exposing them to an increased risk of an adverse event. Luckily, there were no reported adverse events from the subject following the incident. In their response to the 483, the investigator outlined a corrective and preventative action (CAPA) plan that included collaboration between the clinical investigators and clinical research coordinators, verification that the recommended instructed dose adheres to the protocol guidelines, and provision of detailed written dosing instructions for the patients. After review, the FDA determined the CAPA was inadequate as it did not contain sufficient details regarding preventive actions. It is particularly concerning for the safety of the vulnerable pediatric population that a pediatric subject took ten times the dose for seven days and there was an inadequate process in place to ensure this issue would not reoccur. Site’s CAPA responses to 483s are frequently inadequate (see these previous blog entries as examples: Jan 2023, Nov 2023, and Jun 2024). The full warning letter can be found on the FDA website here.
It is important that a site is prepared for an FDA inspection and knows how to properly communicate with the agency and their inspectors. Clinical Pathways offers inspection readiness training that covers all of the steps involved from receiving notice of an upcoming inspection, making sure the site staff are trained on how to interact with the inspector and how to facilitate the process, all the way to responding to FDA findings, including developing a complete CAPA. For a full list of services please visit our website at the following link: https://www.clinicalpathwaysresearch.com/gcptraining.
-The Clinical Pathways Team
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