FDA did not post any warning letters to Sponsors/Monitors/CROs, IRBs or Clinical Investigators this week. From the archives, here is the clinical inspection summary for Erelzi (etanercept-szzs) submitted by Sandoz. Three sites plus the sponsor were inspected. Sites were selected on the basis of high enrollment and protocol deviations. All of the site inspections and the sponsor inspection lasted four days. Once site received a FDA Form 483.
Dr. Kingo was cited for failing to follow the investigational plan, specifically:
- Failing to enter the type of prior therapy into the electronic Case Report Form (CRF).
In reviewing the inspection summary, FDA reports that due to all of the inspections, they were unable to confirm the reliability or reported prior therapy and therefore could not confirm that the protocol required stratification at randomization was accurate. FDA further states that a number of reasons led to this problem: lack of understanding of clinical staff including monitors of the definition and timelines of prior therapy, unclear protocol instructions and the delayed identification of the issue by the sponsor.
The sponsor had to amend the Biologics License Application (BLA) to further describe the issue, which resulted when the Sponsor's contracted data management vendor incorrectly told sites to remove evidence of prior therapy administered more than six months before study start. FDA also notes that the sponsor lacked an adequate electronic CRF to appropriate capture prior therapy. The sponsor was also required to conduct a sensitivity analysis of the impact of the stratification errors that resulted from the impact of the issues with the data surrounding prior therapy.