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FDA Site Inspections

The U.S. Food and Drug Administration (FDA) conducts inspections to protect the rights, safety, and welfare of research study participants, verify the accuracy and reliability of study data, and assess compliance with FDA regulations for the conduct of clinical trials. FDA inspections, or audits, are in-person site visits performed on clinical investigators, study sponsors, or IRBs.

This page provides a general overview of the FDA site inspection process.  Additional details, along with required institutional notifications and actions, are outlined in the FDA Site Inspection Documents.

FDA site inspections are in-person site visits performed on clinical investigators and can be: 

  • Announced or unannounced
  • Routine or for-cause
  • On studies that are open or closed
  • Study-specific or investigator-specific
  • Of a single study or multiple studies

Preparing for an FDA inspection

The investigator must carefully, thoroughly, and accurately document all aspects of the associated study to ensure that the FDA can verify the accuracy of the study data, confirm that participant safety is protected, and determine that the investigator conducts the study in compliance with applicable regulations and the protocol. Routine monitoring is the most important tool for preparing for an inspection at any time and minimizing findings.

Should an investigator receive a notification of an FDA inspection or if an FDA inspector shows up unannounced, the Northwestern University IRB Office has compiled the following resources to guide investigators and staff on navigating an FDA inspection from beginning to end.

FDA Site Inspection Documents 

  • FDA Site Inspection Guidance (HRP-1910): This document contains a comprehensive and detailed guidance for a successful FDA site inspection. It includes recommendations, best practices, and what to expect upon receiving an inspection notification, preparing for an inspection, and during and after an inspection.
  • FDA Site Inspection Preparation Checklist (HRP-2020): This template condenses the inspection preparation information in the FDA Site Inspection Guidance into a general checklist of recommended steps for preparing for an FDA inspection.
  • Inspection Request Tracking Log Template (HRP-2021):  Study teams may use, customize, or reference this template to track all requests made by an FDA inspector.

Notify the Northwestern IRB Office

Before the Inspection

Notify all of the following Northwestern IRB Office contacts upon receipt of any FDA inspection notification so we can prepare and assist study teams in case the inspector has IRB-specific requests:

A full list of entities to notify of the FDA site inspection can be found in the FDA Inspection Documents.

If the study relies on an external IRB, notify the external IRB in addition to the Northwestern IRB Office.  

During the Inspection

Inform the IRB Office if the inspector requests review of the IRB’s internal records, the investigator needs assistance with an IRB-specific request, or the inspector selects additional studies to review while on-site.

After the Inspection

  • If the FDA issues a Form 483: 
  • If the FDA does not issue a Form 483:
    • Inform the IRB Office of the outcome via email with a copy of the final report or written communication from the FDA inspector.
  • If the FDA issues a Warning Letter:
    • Submit a copy of the Warning Letter, the PI’s draft or official response, and CAPA plans to the IRB via an RNI application, and
    • Inform the IRB Office of the RNI number via email.

Frequently Asked Questions (FAQs): 

How does the FDA determine who will be inspected?

The FDA conducts both routine and for-cause inspections. Reasons for an FDA inspection of an investigator may include:

  • Routine surveillance
  • High-enrolling study site
  • Coinciding with the review of a marketing application
  • Based upon current and ongoing public health issues
  • As a result of complaints received
  • As a result of reports of non-compliance
  • Due to sponsor concerns
  • To verify the implementation of corrective actions following a previous inspection

 It is not uncommon for an FDA inspector to select additional studies to review after they arrive on-site.

When should investigators notify the IRB about an FDA site inspection?

Investigators should notify the IRB Office as soon as they receive notice of an inspection. The IRB Office needs to be prepared should the FDA inspector have questions for the IRB or regarding IRB review of the study, and can also guide investigators on inspection preparation and resources.

Investigators should also notify the IRB Office after the inspection has concluded and they have prepared responses to an FDA Form 483 or FDA Warning Letter, or once they learn that there are no inspection observations. The IRB may decide to take additional action based on the outcome or findings of an FDA inspection.

What questions are frequently asked during an FDA site inspection?

Appendix I of the FDA Site Inspection Guidance (HRP-1910) provides several examples of questions frequently asked by FDA Inspectors during their visits.

What happens after an FDA site inspection?

At the conclusion of a site inspection, if the inspector observes serious deficiencies, they will issue a Form 483 during the exit interview, outlining serious findings based on regulations that require correction. Revisions to the FDA Form 483 cannot be made after the inspector leaves. The PI can (and should, whenever possible) respond to issues listed in the Form 483 during the exit interview.

The investigator will also have the opportunity to respond in writing to the findings listed in the Form 483. Responses should include how the PI will be personally involved in taking action and maintaining oversight.

If the investigator does not address the findings to the FDA’s satisfaction, or if the findings are egregious, the FDA may issue a Warning Letter, which they will publicly post on their website. These actions can delay or prevent product approval. It is therefore essential that study teams are always prepared for an FDA inspection.

What is the difference between an FDA Form 483 and an FDA Warning Letter?

  • FDA Form 483
    • FDA Form 483 is a private letter issued at the end of an FDA inspection and includes observations that may constitute federal violations.
    • The FDA Form 483 will be presented and discussed with the PI and contact person(s) at the end of the inspection, before the inspector leaves.
    • The inspector’s observations do NOT represent the FDA’s final determination of their inspection – the final determination is made by considering both the inspector’s observations and the PI’s response.
    • A Warning Letter may be issued if the FDA is not satisfied with the PI’s response to an FDA Form 483.
  • FDA Warning Letters
    • FDA Warning Letters are public letters sent when the FDA identifies significant violation(s) of federal requirement(s).
    • The PI’s response to the Warning Letter is their opportunity to address the FDA’s concerns before the FDA takes legal action.

What actions should be taken after receiving an FDA Form 483 or Warning Letter?

  • Acknowledge receipt of the letter from the FDA immediately
  • Notify stakeholders:
    • Northwestern University IRB
    • External IRBs involved in the research
    • Study sponsor(s)
    • IDS Pharmacy
    • Departments and affiliates involved in the research
  • Create a thorough and well-documented CAPA plan
  • Providing a written response to the FDA within 15 working days

What should be included in a response to an FDA Form 483 or Warning Letter?

A written response, including a CAPA plan to address violations, must be submitted to the FDA within 15 working days.

  • Actions that have or will be taken to correct the violations, prevent future occurrences, and how the PI will be involved.
  • The time at which the actions will be taken
  • Documentation showing the effectiveness of the taken and planned actions
  • Explanations for failure to meet FDA warning letter requirements, such as additional time needed to complete corrections.

Study teams may reach out to the IRB Office Compliance Team (irbcompliance@northwestern.edu) for assistance, as needed, in determining appropriate corrective or preventive actions.

What can happen if an investigator fails to adequately address findings in an FDA Warning Letter?

Failure to adequately respond to an FDA Warning Letter could result in the following, but is not limited to:

  • Funding loss
  • Holds or termination of research
  • Financial penalties
  • Loss of approvals
  • Follow-up inspections
  • Legal action
  • Reputational Harm