FDA Inspection of Clinical Investigators

Before a medicine is launched into market, it undergoes clinical trials to assess the drug’s effectiveness, safety and welfare of humans. Therefore, USFDA conducts a Bioresearch Monitoring (BIMO) program to ensure that clinical investigators abide by the rules and regulations. Under this program, FDA investigators visit the clinical investigation sites, sponsors, Institutional Review Boards (IRBs), contract research organizations and analytical laboratories for inspection.

When is FDA Inspection for Clinical Investigators Conducted?

FDA conducts an on-site inspection of clinical studies to ensure that clinical trials are being conducted in compliance with the regulatory requirements. If clinical trial under consideration is FDA-regulated, the clinical investigators have to allow FDA direct access to all the records, data, reports and subjects’ case histories (21 CFR 312.68).

Clinical investigators must retain the records for at least two years following the approval of marketing application for that drug.

The on-site inspections, announced or unannounced, of clinical investigator in the following circumstances.

  • When the clinical site is terminated

  • If the sponsor has concerns

  • Upon complaints over the clinical studies at an investigational site

  • Upon request of FDA review division

  • To verify the reliability and accuracy of the data provided by the clinical investigator.

How is the FDA Inspection for Clinical Investigators Conducted?

On reaching the site, FDA investigators display their credentials and issue a Notice of Inspection (Form FDA 482) to the clinical investigator or site in-charge. FDA verifies every document, activity and records that the human subjects and investigational products are in compliance with the regulations that govern them.

They ascertain the following concerns:

  • Who is responsible for protocol preparation, inclusion and exclusion criteria, data collection, subject monitoring and collection of adverse event data.

  • Whether the clinical investigators follow the sponsor’s protocol, plans and guidelines.

  • Are the protocols and other amendments approved by Institutional Review Board (IRB)?

  • Record of all the communications between  clinical investigator and the sponsor regarding their financial interests, progress evaluation, protocol deviations or any other issue.

  • How the unused investigational product or waste materials disposed.

  • FDA investigators may also require the medical history of the  human subjects and verify if they fit into eligibility criteria set by the sponsor. It reviews the progress in every subject throughout the period of investigation.

During entire inspection process, the clinical investigator’s staff assisting the FDA inspectors should be well trained on what to say and how to say when asked a particular question. The staff should avoid monosyllables, short phrases and most importantly, “It’s not my job.” They only irritate investigators. Instead, they can simply say, “It’s not my job but I know who is responsible for this activity, please let me see if she is available.”

What Happens After Investigation

Once the inspection is over, the FDA investigator talks to the clinical investigator or their representative over the findings from inspection. They issue a Form FDA 483 in case they found any deficiencies or deviations from the regulations.

The clinical investigator or their staff can respond to it orally during their discussion or give their response in writing after the inspection.

The FDA investigator then prepares a written Establishment Inspection Report (EIR). The District Office forwards all the documents including EIR, Form 483 (if issued) and the response of clinical investigator to the FDA Centre for further evaluation. The guidance in Bioresearch Monitoring (BIMO) program doesn’t legally enforce companies to follow the practices, it only recommends them.