Sites, sponsors, CROs and investigators that start preparing for an FDA inspection when they receive a notice from the agency may already be too late to ensure success. Instead, experts advocate for maintaining a constant state of “inspection readiness” to avoid last-minute problems and surprises.

Marion Mays, vice president of inspection readiness and TMF services at Just in Time GCP, urges sites and sponsors to “begin with the end in mind” when setting up a trial’s procedures, activities and key documents. Establishing an inspection SOP keeps all of a trial’s moving pieces in order and ready to be viewed by regulators and auditors at a moment’s notice.

“Thinking about how you’re going to manage your trial helps you manage all of that activity at the beginning so that you’re not trying to chase things at the end,” Mays told attendees at a recent WCG CenterWatch webinar. “Make sure you’re doing ongoing checks, make sure you’re looking and providing appropriate oversight, and make sure you understand where all of your documentation sits.”

An effective inspection SOP focuses on processes for managing, storing and retrieving key documents. Data integrity is “still top of mind” for the FDA, Mays says, and personnel that conduct inspections, termed “investigators” by the agency, will want ready access to the records and data that tell the story of a trial.

Being able to show the information and the chain of custody of that information is still one of the most important considerations in preparing for inspections, she says, not just for the FDA, but also for regulators in the EU, UK and other countries. “They are very intent on that.”

Mays advises that sites be ready to share and discuss certain documents and records in particular, with records organized, complete and in chronological order to tell the trial’s story in full. Important documents to have ready for inspection include:

• A list of studies performed by the clinical investigator, including protocol numbers and titles, names of sponsors and study dates;
• Dates for signatures on all versions of Form FDA 1572 – Statement of Investigator or the equivalent, as well as dates of first subject screened and consented, first administration of the investigational product (IP), and date of last study visit;
• Investigator brochure;
• All versions of the protocol;
• Curriculum vitae and personal disclosures;
• Protocol training records;
• Sponsor-provided study manual;
• Subject enrollment log (a critical item for demonstrating data validity);
• Lab documents;
• Delegation of authority and site signature log (critical for sites);
• Signed protocol acknowledgement for all protocol versions;
• List of protocol deviations;
• IP accountability records;
• Source documents for all participants enrolled;
• All versions of signed informed consent forms (ICF) for every participant;
• Visit logs and follow-up letters, as well as documentation of action outlined in the letters; and
• Adverse event/serious adverse event documentation.

Inspection readiness also involves understanding the inspection process from the first notice sent by the FDA to the inspection closeout meeting.

Once a site receives an inspection notification, be it by phone or letter, there are a couple of important questions to ask the agency, Mays says.

First, ask about the nature and scope of the inspection: Is it an inspection of a single trial or an overall good clinical practice (GCP) inspection that will involve multiple trials? It’s also important to ask about the number of FDA investigators that will be on site to know how many people you’ll be hosting, she says. The FDA may send a single investigator or a team representing various areas of expertise, for instance. Mays says FDA investigators also may be accompanied by a representative of another regulatory agency serving as an observer or co-inspector. Their presence is growing more commonplace during inspections, she notes.

Similarly, it’s critical to ask how long the inspection may last, including the length of time each day FDA investigators expect staff members to be on call to answer questions and deliver documentation. It’s also helpful to ask for a list of documents the investigators intend to review.

And be prepared for the agency to request information and documents before and possibly after the actual inspection. Digital recordkeeping can make it easy to share files with FDA investigators for remote review — a technique the agency is using more often these days — but document transfer and security procedures must be in place.

Also be aware that the agency is digging into measures sites and sponsors took during the COVID-19 pandemic to keep trials running. You should expect inquiries on this front, Mays says. Whatever the adaptations made during the crisis, they should be well documented and justified. The agency is looking to see that sponsors provided adequate guidance on handling the COVID situation, that deviations were clearly outlined and that information on how activities were to be performed is detailed, she says.

“It’s important that you’re prepared and able to talk about the study and the events that happened,” she says. The process of selecting subjects and obtaining informed consent under pandemic conditions is a critical one. “Those who participated in getting that documentation signed, including the investigator, need to be able to speak to how it was done and the discussions that might have occurred with patients as part of the selection criteria.”

Drug administration is also likely to be in the scope of an FDA inspection, and site staff will need to be prepared to clearly articulate the activities involved in that. Similarly, the pharmacist and pharmacy staff should be ready to explain, in detail, how the investigational product was managed and dispensed. Additionally, Mays urges sites to be on the ball when it comes to the process of determining and identifying data from health records. Be able to clearly explain how and where the information was gathered, whether it was in a system or in paper format, so investigators can review them if they deem it necessary. It’s important that sites are capable of speaking to these in detail, she says.

Another key to inspection readiness is understanding the most common FDA inspection findings. These include failure to follow the protocol, protocol deviations, inadequate participant protections (such as informed consent issues) and failure to report adverse events, as well as inadequate IP accountability, inadequate IRB communications, inadequate evidence of principal investigator oversight and inadequate recordkeeping. Following trends in findings shows where the FDA is focusing its attention and provides valuable examples of what not to do.