Central Lab

Clinical Inspection Summary: Byvalson (nebivolol hydrochloride; valsartan) submitted by Forest Labs

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. 

FDA Clinical Investigator Warning Letter

FDA posted a warning letter to a Clinical Investigator this week. Dr. Giron was warned for failing to follow the investigational plan (21 CFR 312.60), specifically:

  • Failing to collect protocol required Day 1 stool samples and provide them to the Central lab. FDA notes that the PI indicated that he believed samples were shipped as well as analyzed locally.
  • Failing to provide protocol required blood samples (pK, anti-drug antibodies) to the central lab. FDA notes that the PI observed samples being collected and stated that he believed they were shipped to the central lab. 
  • One subject was overdosed for close to a month by taking two extra tablets per day. FDA states "Your failure to ensure that subjects received the correct doses of investigational drug raises significant concerns about the reliability of the data from your site."