FDA Clinical Inspection Summary: Austedo (deutertabenazaine) submitted by Teva

FDA did not post any warning letters to Sponsors/Monitors/CROs, Clinical Investigators or IRBs this week. From the archives, here is the Clinical Inspection Summary for Austedo (deutetrabenazine) submitted by Teva. Two of the thirty participating sites in the study were selected for inspection based on high enrollment and impact on decision making for approval. FDA notes that a statistical methodology was used for site selection. Site inspections ranged over four to eighteen days. One site received a FDA Form 483.

Dr. Claassen was cited for:

  • Two subjects were unable to provide a required blood sample at one visit and the site made arrangements for them to return another date to provide the sample. (Note: The FDA reviewer indicates that the inability to draw blood is understandable and that the action taken in response to the protocol deviation was acceptable.)
  • One subject's medical records indicated excessive alcohol consumption and an attempt to reduce alcohol intake to six beers a week, plus marijuana use on Fridays. FDA notes that this marijuana and alcohol use violate two of the eligibility criteria for the study.
  • Study records for one subject indicated no alcohol use at screening, but two months after screening this was changed to indicate alcohol use. Additionally, three months after screening the amount of alcohol used per week was changed from 1 beer per week to four beers per week with no explanation. 

Note: FDA meetings with the sponsor indicate a concern about alcohol's effect on the activity of the study drug. Study exclusion criteria addressed this.  

The other site that was inspected did not receive a FDA Form 483, but the inspection summary notes issues of prepopulation of some forms to "save time", write overs and inadequate source documentation for some visits. 

FDA Clinical Inspection Summary: Neutroval (XM02) submitted by Teva Pharmaceuticals

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 Neutroval (XM02) submitted by Teva Pharmaceuticals. Two sites, the sponsor (Biogenerix AG) and a CRO were inspected. Site inspections lasted 3-5 days. Both sites and the sponsor were issued FDA Form 483s.

Dr. Zabarskaya was cited for the local lab using hematology analyzers to analyze samples where the results report stated that the reagents used may be expired. 

Dr. Makhson received a citation for failing to have on file documentation indicating that quality control procedures for the hematology analyzers were in place for two years during the study. 

Biogenerix AG was inspected in conjunction with the CRO and was cited for:

  • Failing to conduct the investigation according to the investigational plan, specifically:
    • There were no written records to support unlocking the database twice following unblinding (including a lack of date for the second unlocking) by the CRO
    • Sponsor approval was not obtained for unlocking the database as required by SOP (note the Form 483 was issued to the sponsor)
    • Failing to have a CRO signature on the first unlock form (note this was in the 483 issued to the Sponsor)
    • No database unlock form was available for the second unlock
    • A project manager signature was added to one of the unlock forms retrospectively and backdated with an explanation
    • Database quality control forms were not maintained as required by SOP, including QC checks and randomization for final QC checks

FDA Clinical Inspection Summary of Teva's Cinqair (reslizumab)

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 Cinqair (reslizumab) submitted by Teva. No sites were selected for inspection, as all study sites worldwide had very low enrollment. The sponsor, Teva, was inspected. No form 483 was issued; however the inspectors were instructed to look at four specific items during the sponsor inspection.

  • The inspection was directed to focus on the data fields that were changed post database lock. FDA also noted that the statistical analysis plan for the two studies was finalized after the first database lock, but before study unblinding. 
  • The inspection directed to investigate the process for adjudication of Clinical Events. FDA noted that the submitted eCRF data fields did not appear to be complete enough for proper adjudication.
  • Subjects who were excluded from the safety database were examined closely to determine the incidence of adverse events.
  • The inspection looked carefully at adverse events that FDA noted were of concern during the FDA's review of the submission.