Astra Zeneca

FDA Clinical Inspection Summary: Imfinzi (durvalumab) submitted by Astra Zeneca

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 Imfinzi (durvalumab) submitted by Astra Zeneca. Three sites (out of the 79 that participated in the trial) plus the sponsor were inspected. Site inspections ranged from four days to five weeks. One site received a FDA Form 483.

Dr. O'Donnell was cited for the following (Note: He was the third PI at the site, but was cited for all regulatory violations on the study):

  • Reporting seven Serious Adverse Events outside of protocol required timelines. FDA notes that four of these events were not included in the BLA data listings because the cut-off date was missed.
  • Listing that three subjects had withdrawn consent when they had not. FDA notes that this meant adverse events were not reported as required after the treatment period.
  • Forty-two (42) adverse events were not reported to the sponsor as required for four subjects. FDA required that a sensitivity analysis be performed on the study datasets with the data from this site removed, in order to determine if the under-reporting of adverse events from this site affected study outcomes. 

FDA Clinical Inspection Summary: Lynparza (olaparib) submitted by Astra Zeneca

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 Lynparza (olaparib) submitted by Astra Zeneca. Four sites from the pivotal study were selected for inspection, primarily based on enrollment. Site inspections ranged from 4 days to two weeks. 

Dr. Matulonis was cited for enrolling a subject with clear cell ovarian carcinoma rather than the protocol required serous ovarian cancer.

In addition, during the FDA inspection, the FDA discovered that non-serious adverse events were underreported, as the previous study coordinator was instructed by the previous staff at the Contract Research Organization that non-serious adverse events did not need to be entered on the Case Report Form. For nearly three years, this practice was followed. When the issue was identified, all the data was re-reviewed and the adverse events entered, and provided to the FDA during the application review process. 

FDA Clinical Inspection Summary: Movantik (naloxagol oxalate) submitted by Astra Zeneca

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 Movantik (naloxagol oxalate) submitted by Astra Zeneca.  Four sites plus the sponsor were selected for inspection. Sites were selected based on enrollment and the output of the FDA risk analysis tool. Site inspections ranged over one week to four weeks and the sponsor inspection lasted just over one week. Two sites received FDA Form 483s.

Dr. Foley received a 483 for failing to follow the investigational plan and failing to maintain adequate records, specifically:

  • Enrolling one subject on a prohibited concomitant medication that was known to prolong the QT interval on ECG
  • Enrolling one subject who exceed the limits for QTcF at the screening ECG
  • Enrolling eight subjects without the required cancer screening at baseline. (FDA notes that this was likely a documentation issue, as there was evidence that colonoscopies had taken place.)
  • Enrolling one subject who was not on a stable dose of opioids
  • Discrepancies for three subjects in opioid doses

Dr. Sanapati was cited for failing to follow the investigational plan, specifically:

  • Enrolling two subjects who were taking protocol prohibited medications that prolonged the QT interval