IV. Post-FDA inspection

  • Inspection Summary Report

  1. Immediately after the visit, a detailed report summarizing the inspection should be written (by the PI or the person designated to coordinate the inspection) based on the inspection notes. The report should be kept with essential study documents and include:
    1. A summary of questions and discussions between inspector and each employee.
    2. List of all studies or facilities/departments viewed.
    3. List of all records reviewed.
    4. Copies of all documents duplicated for the inspector.
    5. Note of all samples taken, and receipt for samples.
    6. Note of all commitments made (include completion dates if set with FDA).
    7. Comments of inspector related to inspection.
  • Response to FDA report

  1. Upon receipt of a report from the FDA, the PI/research team should email an electronic version of this document to the Compliance and Education Specialist. The following steps describe how to proceed whether the findings are significant (Form 483) or non-significant.
  2. If the outcome of the report is significant and results in the receipt of a Form FDA 483, the appropriate individual(s) shall draft a response. See "Reporting to the IRB of Record" below for examples of when the University’s HSO/IRB and/or Office of the General Counsel may assist the PI in drafting a response.
  3. The PI is responsible for the response content and for sending the written response within 15 working days.
    1. If you are unaccustomed to responding to a Form 483, having someone with prior experience provide assistance is beneficial, so either consult with your administrator and/or,
    2. Consult with Privacy Officer if the response involves PHI c) Consult with Pharmacy Administrator if the response is related to study drugs
  4. The written response should:
    1. Address each particular observation or finding, point by point.
    2. Determine if a finding was an oversight/one-time occurrence or systemic, where a change of procedure is indicated.
    3. If the PI disagrees with an observation, respond factually and provide clear and verifiable evidence.
    4. Delineate corrective and preventive action (CAPA): include justification of why the proposed response will remediate the issue and a realistic timeline for implementation.
    5. Keep a copy of the final signed response in your records along with all attachments.
  • Reporting to the IRB of Record

  1. If the UI is the IRB of record, and:
    1. If the outcome of the report is significant and impacts the current status of the study, the PI should submit a HawkIRB modification to address the finding(s), at the time the ‘483’ is received. If necessary, the IRB will confer with the University’s Office of the General Counsel and seek assistance in formulating the written response to the FDA. Significant findings could include items such as the following:
      1. PI did not conduct the research study according to the investigational plan (i.e., protocol and HawkIRB application).
      2. PI failed to maintain adequate case histories with respect to observations and data pertinent to the investigation.
      3. PI failed to obtain informed consent or maintain all pages of the signed Informed Consent Documents for each enrolled subject. iv. PI failed to report to the sponsor, per reporting guidelines, adverse effects that may reasonably be regarded as caused by, or probably caused by, an investigational drug.
    2. If the outcome of the report is non-significant and does not impact the current status of the study, the PI should report in the next Continuing Review that s/he has been monitored by responding ‘Yes’ to Section CRIII.12 and attach the FDA Inspection Report in the Continuing Review Attachment section.
  2. If UI is not the IRB of record, and:
    1. If the outcome of the report is significant and impacts the current status of the study, the Education and Compliance Specialist will:
      1. Document the outcome information in the FDA Inspection Report
      2. Present the report findings to the HSO Director (in case the findings warrant additional guidance from the Institutional Official and/or General Counsel).
      3. Notify the external IRB of Record of the FDA inspection.
    2. If the outcome is non-significant and does not impact the current status of the study, the Education and Compliance Specialist will:
      1. Document the outcome information in the FDA Inspection Report
      2. Remind the research team that they must adhere to the reporting policies and procedures as outlined in the reliance agreement with the external IRB.
      3. Notify the external IRB of the FDA inspection.
  • Sponsor Notification

  1.  The PI should notify the sponsor of the issuance of a Form FDA 483 and provide the sponsor with a copy of the PI’s formal written response to the FDA; moreover, the PI should review his/her other clinical trial agreements and grant documents for any requirements regarding notification to other sponsors whenever inspection of an unrelated study results in issuance of a Form FDA 483.
  • Inspector’s EIR (Establishment Inspection Report)

  1. The FDA inspector will file an EIR within approximately 30 days. This report is subsequently available through the Freedom of Information Office (FOI) after the conclusion of any follow-up by the FDA to Form 483, Warning Letter, or other actions arising from the inspection.
  • Additional Action

  1. The FDA considers all information provided in response to the Form 483 and then determines what further action, if any, is appropriate to protect public health.

FDA Warning Letters summarize inspections of clinical investigators and these are posted on the FDA website.

University of Iowa Human Subjects Office and Institutional Review Board Site Inspection Guide
Title: FDA Site Inspection Guide

Effective Date: 1/19/2016

Signed by:

Version: 1
Approved by: HSO Director Michele Countryman  
Approved by: IRB Primary Chair J. A. Bertolatus  
Approved by: Institutional Official Heather Gipson  
Annual review    

Acknowledgement to the University of Wisconsin-Madison’s Institute for Clinical and Translational Research (ICTR) Study Monitoring Service as the primary source of information (in particular the intake form courtesy of https://ictr.wisc.edu/CRToolkit), and the Children’s Hospital of Philadelphia Office of Research Compliance and Regulatory Affairs for the Frequently Asked Questions (FAQs). Adaptations and edits made by the UI HSO/IRB Compliance Program in consultation with the UIHC Joint Office for Compliance.