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SOP on FDA Inspection-Clinical Trial Site Management

SOP on FDA Inspections at Clinical Sites

Introduction and Purpose:

The U.S. Food and Drug Administration (FDA) conducts inspections to ensure the rights, safety, and welfare of subjects involved in FDA-regulated clinical trials are protected, to determine the accuracy and reliability of clinical trial data, and to determine if the study has been conducted in compliance with FDA regulations. The most common type of inspection is classified by the FDA as a “Routine” inspection and is generally triggered by a marketing approval submission. Clinical sites with the highest enrollment numbers in the pivotal trials are the most likely candidates for a routine inspection. “For Cause” inspections are less common, and generally are conducted to investigate a specific problem that has come to FDA’s attention.

The Office for Human Research Protections (OHRP) within the U.S. Department of Health and Human Services may also initiate and conduct inspections of clinical trials. The responsibilities, notification, conduct, and response to OHRP inspections should follow the same procedures and requirements in this SOP, as applicable.

The purpose of this SOP is to outline the processes for the preparation, conduct, and response to an FDA inspection of a clinical trial at the clinical site.

Definitions and Acronyms:

  • Clinical Research: All research involving human participants.
  • Clinical Trial: Research studies involving human participants assigned to an intervention designed to evaluate its effect on health-related outcomes.
  • CAPA: Corrective and Preventative Action.
  • ERICA: Electronic Research Integrity Compliance Administration.
  • FDA: United States Food and Drug Administration.
  • GCP: Good Clinical Practice.
  • HIPAA: Health Insurance Portability and Accountability Act.
  • IC: Inspection Coordinator.
  • IDE: Investigational Device Exemption.
  • IND: Investigational New Drug application.
  • IRB: Institutional Review Board.
  • OHRP: Office for Human Research Protection.
  • PHI: Protected Health Information.
  • PI: Principal Investigator.
  • SOP: Standard Operating Procedure.
Procedure:

Notification and Scheduling an Inspection:

  • The FDA inspector should contact the study PI to schedule an inspection. Immediate notification of the PI must take place if another study team member is contacted.
  • Gather necessary information at the time of initial notification, including the purpose and scope of the inspection, inspection details, and contact information.
  • Notify relevant parties, including the Institutional Review Board administration, Clinical Trial Sponsor, Clinical Research Support Office, Associate Dean for Clinical Research, and Investigational Drug Services administration.
  • Identify an Inspection Coordinator (IC) within the department to oversee the inspection process and document all details.

Preparation for the Inspection:

  • Ensure key study personnel are available during the inspection period.
  • Reserve a suitable inspection room.
  • Prepare a summary of the clinical trial(s) selected for inspection.
  • Compile a list of FDA-regulated studies conducted by the investigator.
  • Review and organize study documents likely to be inspected.
  • Ensure compliance with HIPAA for review of electronic medical records.
  • Coordinate potential assistance from the clinical trial sponsor in the inspection preparation.
  • Inform study personnel of pre-inspection findings.

Conduct of the Inspection:

  • Verify the credentials of the FDA inspector.
  • Escort the inspector to a reserved room.
  • Do not offer food or social interaction during the inspection.
  • Hold an initial meeting to establish the inspection agenda.
  • Provide requested study records selectively.
  • Document all interactions and questions during the inspection.
  • Accompany the inspector during physical facility inspections.
  • Discourage photography that may capture protected health information.
  • Arrange interviews with relevant study staff if requested.
  • Provide honest and concise answers to inspector questions.

Post Inspection:

  • Review the Record of Inspection for completeness.
  • Generate an inspection summary report if appropriate.
  • Provide a copy of the FDA 483 to the IRB administration and clinical trial sponsor.
  • Prepare a response to inspectional observations within 15 business days.
  • Address each observation separately with factual, clear responses.
  • Develop corrective and preventative action (CAPA) plans.
  • Submit the FDA 483 and response to the IRB.
  • Notify General Counsel in case of affidavit requests.
  • Report additional FDA communications to the IRB and General Counsel.

Materials Required:

  • Notice of FDA Inspection (FDA 482).
  • Study records and documentation.
  • Notes of FDA inspector comments and requests.
  • Duplicate copies of all documents provided to the inspector.
  • Inspectional Observations (FDA 483).
  • Other FDA communications and PI/institution responses.

References:

  • 21 CFR Part 312.62: Investigator Recordkeeping and Record Retention.
  • 21 CFR Part 312.68 Inspection of investigator’s records and reports.
  • 21 CFR Part 812.145 Inspections (devices).
  • ICH Guidance for Industry E6(R2): Good Clinical Practice.
  • FDA Information Sheet Guidance, June 2010: FDA Inspections of Clinical Investigators.
  • CRCE Procedure: Governmental Agency Audits.

Document Approval:


Revision History:

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