A Food and Drug Administration (FDA) inspection of an investigational site can occur at any time, and preparation is critical to an efficient inspection. By understanding what the FDA typically looks for in its inspections, sites can make sure all documentation is ready for review and all staff are properly trained to interact with the inspector. Proactive preparation can help ensure the inspection goes as smoothly as possible, avoiding burdensome follow-up and the possibility of a Form FDA 483, inspectional observations.
Although some inspections may come at a trying time, they are meant to protect the rights, safety, and welfare of human research subjects; to verify the accuracy and reliability of clinical trial data submitted to the FDA; and to assess compliance with FDA’s regulations governing the conduct of the clinical trial. Inspections can happen for multiple reasons, including a new drug application, complaint, safety issue, or just a routine inspection. The FDA’s regulations are meant to govern the conduct of a clinical trial, including regulations for investigators, informed consent, and ethical review. In this three-part blog series, we will recap what to do when preparing for an inspection, during an inspection, and after the inspection.
How to Prepare for an Inspection
While preparing for an inspection, having a site-specific process for supporting a regulatory inspection is important as it will identify who does what before, during, and after a regulatory inspection.
Site personnel should decide on how the site would physically coordinate the office to accommodate the regulatory inspector(s) (also called Office of Regulatory Affairs (ORA) investigators) and decide which staff will act as host and which staff will work to coordinate the inspector(s) document requests. All staff, including the principal investigator (PI), sub-investigator(s), study coordinators, and other pertinent team members should meet to review all activities for the study under investigation. This includes review of the protocol, the subjects enrolled, and delegation of study procedures. Additionally, site personnel should prepare to discuss topics such as:
- Protocol training
- Subject recruitment
- Informed consent process
- Study specific procedures
- Source documentation
- Data entry
- Investigational product handling
- Ethical reviews and approvals
Prepare for your interview with the inspector(s). Re-read the protocol, study procedures and study manual. Recall who did what in the study. If any issues happened during the study, have an explanation. For example, were there protocol deviations? Why did they occur? What actions were taken to prevent future occurrences?
When this is a site’s first FDA inspection, staff can become very anxious about interviewing with an FDA inspector. One way to decrease anxiety is to role play the interviews. As the study staff practices interviewing techniques and reviews their role in the study, they should become more confident.
The site should ensure all study documents are readily available. If study records are archived off-site, all records should be recalled and available for the inspection. Review the records to confirm they are complete and ensure the inspector can open and review any electronic records. If the site is missing any documents, check with the sponsor/contract research organization (CRO) to see if a copy is in the trial master file (TMF) and the sponsor/CRO can send a copy of the document to the site.
The inspector(s) will expect the site to provide multiple documents containing information about the site’s organization. At the start of the inspection, the inspection host should provide the inspector(s) the site’s organizational chart, discuss the site’s reporting structure, and provide the standard operating procedure (SOP) index, as well as an overview of how the study documentation is organized.
In order to properly prepare for the inspection, it is important to understand what the inspector will look for and ask about. The inspector(s) will request to see the study documents. Do not provide the inspector(s) with all the study documents and essential documents, provide them only with the documents requested. For example, if they requested to see all the signed Form FDA 1572s, do not bring in the Investigator Site File where the Form FDA 1572s are filed. Remove the forms from the file before providing them to the inspector(s). Upon review of the Form FDA 1572s, the inspector(s) will request the PI’s and all listed sub-investigators CVs, medical licenses, as applicable, and financial disclosure agreements.
The inspector(s) will request to see documentation of protocol and amendment training, delegation of responsibilities, the screening and enrollment logs, and informed consent forms (ICFs), including ICFs for any screen failures. The inspector(s) will select several or all subjects screened and enrolled in the study for review of their source documents, including all available medical records. If the study used an electronic data capture (EDC) system and it is still active, the inspector(s) will request access to this system. If the database is closed, the inspector(s) will review either data listings or they might have access to case report forms (CRFs) from the sponsor.
Inspectors will also conduct source data verification (SDV) and source data review (SDR). SDR is the review of source documentation to check on protocol compliance and staff involvement. SDV is the process by which data within the CRFs are compared to original sources of information to confirm accurate data transcription. Source data is original records and certified copies or original records of clinical findings, or observations (ICH E6 R2 1.51).
Ensure the inspection review area is quiet and away from other offices and clinical areas, if possible, to prevent the inspector(s) from potentially overhearing confidential conversations. Additionally, ensure the inspection host is always available to stay in the inspection review area with the inspector(s). To keep the inspection moving as efficiently as possible, assign a designated copier and printer, if possible. The inspector(s) may request copies of any of the essential documents or source documents they review.
What are the next steps? Check out our subsequent blog, FDA Inspection Readiness: During an Inspection.
Looking for additional help? Get expert support on virtual audits, document QC/QA, regulatory inspections, and more.