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  • Catherine Schmidt

When the FDA Visits your ETMF

Updated: Dec 22, 2022

What is an FDA Audit really like? Roni Martinez, Manager of Document Control at Cidara Therapeutics and SterlingBio's Catherine Schmidt discuss.


Catherine Schmidt, Dec 21, 2022 - Clinical trial systems and processes are advancing at a fast rate. We’ve come a long way from truckloads of paper document files and 3-part NCR case report forms. One thing has not changed quite so dramatically: The FDA Audit.


Before a new drug, device or biologic can be reviewed and approved for human use, US Food and Drug Administration (FDA) will usually dispatch an FDA auditor to review the clinical trial data and documentation at the sponsor’s (or CRO’s) office and may also audit selected clinical study investigator sites.

Sponsors typically work very hard to prepare for an FDA audit, which can be scheduled by the FDA with very little advanced notice. Sponsors create written procedures to host audits, pay for “mock audits,” perform nearly constant trial master file readiness reviews and practice roles and responsibilities to be prepared for the big event.

In addition to the management of clinical trial participant data, the collection and maintenance of clinical trial documents is a huge component in the execution of clinical trials. The FDA’s code of federal regulations (CFRs), as well as ICH Guidelines lay out the list of essential documents that must be collected for a clinical trial. Managing and tracking these documents have become somewhat easier in the advent of electronic trial master files (eTMF), but the digital nature of document management has its own challenges.

How do FDA auditors handle review of the eTMF during a sponsor or CRO audit? In past years, the FDA could only inspect electronic records by overseeing the firm’s personnel while the firm’s user accessed the system. This is not practical since firm personnel had to be dedicated to the task during the entire inspection visit. However, the FDA’s Inspection Operations Manual section 5.10.2.1 FDA Guideline was updated in 2021 to allow for auditors to gain read-only access to databases under certain conditions, including written permission to access, necessary training is completed, access is documented in the inspection report, etc.

We wanted to find out what a recent actual FDA audit of a clinical trial eTMF database was like. We spoke with Roni Martinez, Manager of Document Control at Cidara Therapeutics.


“We felt prepared. Our mock audit of our large multinational trial went great,” explained Roni. “We weren’t sure what the FDA auditor would ask to see, but we were ready to give the FDA auditor read-only access to our eTMF.”

It turned out that the auditor did not want to have direct eTMF access, but rather he provided a list of documents to the sponsor and asked for those documents to be uploaded to the FDA portal.


“This made the audit a little less stressful,” admits Roni. “Luckily, document search and retrieval from our eTMF was easy and I was able to send those documents to our QC department for uploading to the FDA portal.”


In addition to requesting copies of clinical trial documents, the auditor was very interested in data about the eTMF. “He asked for information regarding system versions, dates used, validation information, etc. Again, we were prepared for this since our eTMF system included a Compliance Portal where I could access this information to provide to the auditor,” said Roni.


This story has a happy ending. “The audit was CLEAN! No findings!” exclaimed Roni.


Tips for FDA Audits of eTMFs:

  1. The inspector may or may not request read-only access to the eTMF. Section 5.10.2.1 of the Inspection Operations Manual can help you be prepared in case access is requested.

  2. Practice and be ready to search and retrieve documents out of the eTMF for the inspector

  3. Keep your eTMF validation information, version update information and audit trails readily available



SterlingBio would like to thank Roni Martinez for her valuable input!

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