FDA did not not post any warning letters to Sponsors/Monitors/CROs, IRBs or Clinical Investigators this week. From the archives, let's have a look at the clinical inspection summary for Amgen's Repatha (evolocumab). Across the three studies submitted as part of the BLA, five clinical sites (each participating in at least two of the studies) were selected for inspection.
Dr. Awasty received 483 for two studies (66002 and 66080). Findings included:
- Failing to follow the investigational plan: Administering the investigational product before conducting the ECG as required per protocol.
- Failing to follow the investigational plan: Recording blood pressure from one arm only for 12 of 13 subjects when the protocol required that blood pressure be recorded from both arms at screening.
Other notable items from this inspection summary that were noted, but without a Form 483 being issued include:
- A missing page with PI contact information for one subject's consent document at Dr. Awasty's site.
- Incomplete documentation of the presence of a translator at Dr. Bolognese's site when Spanish-speaking subjects were consented.
- Subjects dating the informed consent document with their birthdates and skipping the primary care notification checkbox at Dr. Hala's site.
- Source notes from subject physical exams noting changes without corresponding adverse events recorded at Dr. Hala's site.
- Failure to report complaints about the auto-injector to the sponsor at Dr. Krogsaa's site. (FDA notes that the complaints were reported during the inspection.)
- Drug accountability at Dr. Krogsaa's site indicated that 77 tablets could not be accounted for, and that study staff sometimes dispensed more drug than was needed to subjects.
- Incorrect source documents led to incorrect randomization of four subjects at Dr. Krogsaa's site. FDA notes that the IVRS system could not fix this.
- Two adverse events were not reported at Dr. Lasko's site.
- One subject signed an outdated consent form at Dr. Lasko's site.
- A disorganized drug accountability log at Dr. Lasko's site.
- The Investigational Product Instruction Manual did not provide guidance if more than one syringe malfunctioned at one time. Dr. Lasko's site recorded two complaints on the same form.
- During the sponsor inspection, FDA noted that an ineligible subject was enrolled at Dr. Bolognese's site.