FDA Cites Part 11 in Clinical Trial

Just when you think you know what to expect from the FDA, they go and shake things up.

This is a developing story, but the implications for companies involved in clinical trials are clear.

Both European and US regulators expect data integrity when it comes to clinical data and are increasingly willing to cite problems found during inspections.  

Rethink What You “Know”

We all “know” FDA doesn’t cite Part 11 in 483s, right?

Well, maybe.

FDA podium-speak has been that the software inspectors use to track findings does not allow Part 11 citations, that they must go back to predicate rules instead.

However, it is time to rethink that.

Until now, the only example we’ve seen of a Part 11 citation in clinical trials was the 2016 inspection of Clinical Investigator Dr. Cassandra Curtis that resulted in a Warning Letter.

Dr. Curtis’ 483 stated, “Electronic records are used, but they do not meet requirements to ensure they are trustworthy, reliable and generally equivalent to paper records.” In this case, the observation was aimed at discrepancies in the electronic medical records used by Dr. Curtis to record source data for clinical trial subjects.

Immunomedics 483: A Sign Of Things To Come?

In the most recent Part 11 example, FDA cited Immunomedics, as the Sponsor of clinical trials, for using electronic records that “do not meet systems validation and audit trail requirements to ensure that they are trustworthy, reliable and generally equivalent to paper records.”

The 483 goes on to state, “Specifically, Immunomedics utilized the computer program (b)(4) to record data from each of the clinical site’s (sic) Case Report Forms (CRFs), including Adverse and Serious Adverse Events, from inception through May of 2017 for the reporting of clinical data to FDA. The program was not validated, and an audit trail to monitor use was not implemented.”

It is not clear yet what kind of system was at issue. Possibilities include:

• Electronic Data Capture (EDC) system deployed by Immunomedics to the clinical sites
• System used at Immunomedics to transform data recorded by the clinical sites on paper CRFs into usable electronic records
• System used at Immunomedics to extract and store clinical data from an EDC system

Is FDA Catching Up?

21 CFR Part 312 comes “straight from the 80s,” and does not account for the complexities of today’s clinical trials.

Is FDA following the lead of European regulators and taking the data integrity problems they see at investigator sites back to the sponsor? Is FDA finding ways to deal with “CROs” that aren’t CROs? Or is FDA learning to address the complexities of how sponsors manage clinical data from multiple, disparate sources?

We’ll share more as we learn more in this developing story…