Sponsor

FDA Clinical Inspection Summary: Vizamyl submitted by GE Healthcare

FDA did not post any warning letters to Sponsors/Monitors/CROs, IRBs and Clinical Investigators this week. From the archives, here is the Clinical Inspection Summary from GE Healthcare. Of the five locations inspected, all were sponsor locations or sponsor vendors. 

The sponsor received a 483 for failing to monitor, specifically:

  • One site exceeded IRB-mandated enrollment limits without approval. Another site exceed the enrollment cap sixteen days before receiving approval to do so. 
  • The monitor failed to follow up when two sites did not submit the required IRB closure form
  • A subinvestigator performed two study related procedures (autopsy and geneotyping) and wasn't listed on the FDA Form 1572. At another site, one subinvestigator performed five autopsies and was not listed on the FDA Form 1572. 
  • Three subinvestigators at one site had not submitted financial disclosure forms.
  • At another site, two subinvestigators did not sign financial disclosure forms. FDA notes that aside from a one time reminder, the monitor did not follow up to collect the form for one subinvestigator. 
  • At one site, six of 10 ECGs were not performed within protocol specified timeframes

FDA Warning Letter: Entellus Medical

FDA posted a warning letter this week to a device sponsor. 

Entellus Medical was warned for:

  • Failing to secure compliance of noncompliant investigators
    • FDA notes that sponsor employees were present at procedures that did not comply with the approved trial protocol
    • FDA notes that the eighteen pre-planned protocol violations were not reported to FDA
  • Failing to receive FDA and IRB approval prior to implementing a change to the investigational plan
    • FDA states that the pre-planned protocol deviations were encouraged
    • FDA notes that the pre-planned protocol deviations were documented in monitoring visit reports
  • Failing to notify the FDA and IRB of significant new information
    • FDA notes that FDA was notified of the protocol deviation upon submission of the Annual report
    • FDA notes that the IRB was notified after the FDA inspection
  • Failing to submit changes in the investigational plan to the FDA and IRB prior to implementation
    • FDA states that study subjects were placed at an increased risk of harm

FDA Sponsor-Investigator Warning Letter

FDA posted a warning letter this week to a Sponsor-Investigator. After an inspection that ranged over one month, Dr. Benson was warned for the failing to follow the investigational plan, specifically:

  • Dosing two subjects without platelet testing within the prior two weeks, contrary to protocol requirements
  • Enrolling one subject with renal insufficiency, contrary to protocol requirements
  • Failing to perform a total of seven laboratory tests across five subjects, including urinalysis, uric acid, magnesium and phosphorous

FDA Sponsor-Investigator Warning Letter

FDA posted a warning letter this week to a Sponsor-Investigator

Targeted Medical Pharma, Inc. was warned for:

  • Failing to submit an IND
    • The company responded to the 483 received after the inspection by stating they were testing a medical food. The FDA warning letter reviews the criteria for medical food and determines that this threshold was not met.
    • The company responded to the 483 by stating an employee had "reached out" to the FDA and been told that the product was a medical food but an IND "should still be applied for". The company states that a Form 1571 and Form 1572 had been submitted to the agency in the 483 response. FDA states that no IND number was assigned and there is no evidence that the forms were ever submitted. 
    • FDA notes that under two protocols, two hundred and fifty one subjects were enrolled across multiple sites for the trials. 

FDA Sponsor-Investigator Warning Letter

FDA posted a warning letter this week to a Sponsor-Clinical Investigator. 

Dr. Burt was warned for:

  • Failing to ensure that the study was conducted in accordance with the investigational plan in the IND, specifically:
    • Failing to report Grade 3 adverse events in two subjects at one site to FDA in annual reports, as required by the protocol.
    • Failing to ensure four sites reported adverse events, as required by the protocol. FDA notes that there was no adverse event CRF designed for the study.
    • Failing to report two deaths on study to the FDA as required by the protocol.
    • Failing to review three adverse events during the course of the study to determine if they required reporting to FDA
    • Failing to conduct the interim analyses required by the protocol.
  • Failing to submit a protocol amendment to the IRB
    • The protocol was amended when new investigators were added to the study, but these three protocol amendments were not submitted to FDA
    • A total of nine protocol amendments were not submitted to FDA
  • Failing to select qualified investigators
    • The sponsor investigator was unaware of the training and qualifications of one site and eventually that one site was suspended from the trial for enrolling ineligible subjects.
    • The stated selection criteria for three other sites was "knowledge of professional reputation"
  • Failing to obtain CVs, Financial disclosure and FDA 1572s from participating sites.
  • Failing to provide an investigator brochure.
  • Failing to monitor study progress
    • No onsite monitoring was performed
    • There was no evidence of other types of monitoring
  • Failing to submit annual reports
  • Failing to review adverse events at his own site, as required by the protocol.
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