IRB

FDA Clinical Inspection Summary: Calquence (acalabrutinib) submitted by Acerta Pharma

FDA did not post any warning letters this week to Sponsors/Monitors/CROs, IRBs or Clinical Investigators. From the archives, here is the recently posted clinical inspection summary for Calquence (acalabrutinib) submitted by Acerta Pharma. Two sites (out of forty participating in the trial )plus the sponsor were inspected. Site inspections lasted two and five days. Sites were selected on the basis of high enrollment and potential contribution to efficacy. The sponsor inspection lasted two weeks.

The sponsor received a FDA Form 483 for failing to monitor the study properly, specifically:

  • Failing to ensure sites submitted protocol amendments to the IRB in a timely fashion. Delays were noted to be four to eleven months. 
  • Failing to assure investigators and subinvestigators documented training.

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 IRB Warning Letter: Oeyama-Moto Cancer Research Foundation IRB

FDA posted a warning letter to an IRB this week. Oeyama-Moto Cancer Research Foundation IRB was warned for:

  • Failure to develop, maintain and follow written procedures for the operation of the IRB as required by 21 CFR 56. FDA notes that the IRB's response to the original Form 483 contained a discussion of the procedures for conducting clinical investigations.
  • Failure to prepare and maintain adequate documentation of IRB activities, including meeting minutes. FDA notes that vote counts were not always recorded, and attendance was not always recorded which brings into question if IRB members with a conflict of interest recused themselves from voting on studies they participated in. FDA notes that the IRB appears to have approved one study by a coin toss, and transferred a low dose patient group to a higher dose for "humanitarian reasons." 
  • Failure to notify an investigator in writing of approval or disapproval of research or modifications to research. FDA notes that the response to the original 483 referenced items that were not provided to the FDA. 

FDA IRB Warning Letter: Pikeville Medical Center

FDA posted a warning letter to the Pikeville Medical Center last week for the following items:

  • Failing to maintain written procedures as required by 21 CFR 56
  • Failing to adequately document activities, including maintaining meeting minutes. FDA specifically notes that vote counts were not always recorded.
  • Failure to achieve a quorum for review of research
  • Failure to review studies at least once per year

Throughout the warning letter, FDA discusses that the initial response from the IRB was to transfer governance of the IRB to the hospital board of directors. FDA notes that this response is inadequate, because it is unclear what the board of director's role will be and no procedures were submitted as part of the warning letter response.

FDA IRB warning letter: Jamaica Hospital Institutional Review Board

FDA issued a warning letter to an IRB this week. Jamaica Hospital Institutional Review Board was warned for:

  • Failing to prepare and maintain adequate documentation of IRB activities, specifically:
    • Five instances where IRB meeting minutes did not document specific vote counts on FDA regulated studies
  • Failure to maintain up to date membership lists over two years