FDA did not post any warning letters this week to Sponsors/Monitors/CROs, IRBs or Clinical Investigators. From the archives, here is the Clinical Inspection Summary for Byvalson (nebivolol hydrochloride; valsartan) submitted by Forest Labs. Three sites were selected for inspection. Two were selected on the basis of high enrollment and high treatment effect size, as well as a number of previous trials (13 and 5 respectively) with no previous FDA inspections. The third site was selected due to high enrollment, as well as a sponsor complaint on a different trial five years ago and a previous FDA inspection with a 483. Site inspections ranged from 3 to 14 days. Two sites received FDA Form 483s.
Dr. DiGregorio was cited for failure to follow the investigational plan, specifically:
- Failing to use the local laboratory urinary drug screen results to randomize five subjects, as required by the protocol. (FDA notes that central laboratory results were used.)
- Failing to use serum pregnancy results from the central laboratory to randomize four subjects as required by the protocol.
- Failing to perform vital sign measurements on the day of randomization for three subjects as required by the protocol.
- Failing to perform hematology labs on the day of randomization for one subject.
- Failing to perform end of treatment pregnancy testing for one subject.
- Administering increased doses to six subjects one day earlier that the protocol permitted.
- Failing to perform protocol required follow up for one subject who had a prolonged QTc interval at the End of Treatment Visit.
Dr. Lara was cited for the following:
- Failing to follow the investigational plan by randomizing three ineligible subjects (one had a history of gastric bypass, one had a right bundle branch block evident in the ECG and one had an out of range ECG value at screening).
- Failing to report to the IBR the three ineligible subjects who were randomized.