Since opening our doors nearly 10 years ago, GuideStar experts have routinely been engaged by clients and potential clients with questions about the best ways to successfully prepare for an FDA audit. As this information is valuable to all sites conducting industry sponsored clinical trials, we are providing this guide on what to expect during an FDA Audit to help you put your site in the best position possible should it need to undergo an audit.
Purpose of an FDA Audit
To prepare for an FDA audit, it is best to know why they occur. The FDA Office of Regulatory Affairs performs inspections of the activities of sponsors, monitors and investigators at research sites. Research activities under New Drug Applications (NDAs); Investigational New Drugs (INDs); and Investigational Devices (INDs) are all subject to FDA auditing.
Breaking the process down even further, the agency’s first responsibility during an audit is to ensure that the rights, safety and welfare of research subjects are protected. And, while subject protection is priority number one, the FDA will also spend a significant portion of the audit making certain of regulatory compliance, process validation and accurate study data submission at the site.
The way that the FDA auditor meets these responsibilities is by inspecting and verifying how your site is conducting a clinical trial. The FDA auditor will evaluate the ethical conduct of human subject research and the integrity of previously reported data. A site’s adherence to the study protocol, along with applicable institutional, state and federal regulations, and guidance documents will also be evaluated.
To help with compliance, the FDA Office of Regulatory Affairs provides program manuals specific to IRBs, Clinical Investigators, and Sponsors. All of these are great references to better ensure that your program maintains compliance.
Types of Audits and Their Triggers
There are two types of audits – Routine Audits and For-Cause Audits.
Routine Audits are randomly conducted as a checkup on the operations of a clinical research site. These types of audits are not conducted due to any implication of oversight or wrong doing on behalf of the site, itself.
For-Cause Audits are exactly what they sound like; the FDA has been given a reason to check in on a research site by way of a complaint.
A complaint can come from any source, whether by a study participant, someone on the research staff or an anonymous source. Regardless of the source, if the FDA receives any feedback about a concern at a site, the agency will want to address the issue, first-hand.
In the same vain, if a sponsor or the IRB shares a concern about a research site with the FDA, a For-Cause audit will occur.
Any of these triggers may be related to a wide variety of issues, including screening practices or protocol adherence, deviations from the protocol, unusual adverse events, or if the site has recently been terminated by another sponsor or IRB.
How an Audit is Conducted
Upon arrival at the research site, the inspector will display his or her FDA credentials and Notice of Inspection, also known as the FDA Form 482, to the site administrator. This documentation gives the FDA the authority to access, inspect and copy any records related to the clinical investigation. The auditor will likely speak with any individuals involved in conducting the trial.
The FDA inspector will review a number of areas during the audit, such as:
- Was the protocol followed?
- Were SOPs followed?
- What are the qualifications of the study personnel?
- Is specific documentation of informed consent present?
- Were adverse events documented and reported appropriately?
- Were deviations documented and reported appropriately?
- How did the clinical investigator delegate and supervise study tasks?
- Was appropriate accountability of investigational product maintained?
- Review any financial interests reported by the clinical investigator
- Review documents such as IRB approval of the protocol, informed consent form, and amendments
Even after all of this information, FDA audits may still seem incredibly daunting, so additional resources are listed here for further reading. The FDA has a comprehensive FDA Compliance Program Manual as well as a Guide for FDA inspections. These resources will provide you with in-depth details as you prepare your organization’s FDA Ready SOP or to prepare for an actual FDA Audit
FDA Compliance Program Manual www.fda.gov/ora/cpgm/default.htm
FDA Inspection Guides http://www.fda.gov/ICECI/Inspections/InspectionGuides/default.htm
This extensive, and likely unplanned audit process is part of why GuideStar considers it a best practice to regularly train the research staff on FDA Audit procedure. To be fully prepared, consider performing mock audits within your site to prepare research staff should the FDA schedule a visit. An FDA audit is never a fun process, but proper preparedness on the part of the site can keep it from being an unpleasant and overwhelming experience.