What to Expect When the FDA Comes Calling

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Patrick Stone, President, TradeStone QA

Enduring data validation audits and for-cause audits for human clinical trials involving biologicals, devices, or new chemical drugs may at first remind some of going to the dentist to get your wisdom teeth pulled.

But, the FDA has just as much at stake as your company does in the products marketed in the U.S., because if there is a problem or unsafe conditions FDA gets blamed for not doing enough.  That’s top of mind for most inspectors and important for regulated entities to remember.

With that in mind, let’s examine industry trends for these types of inspections.

Lets start by what Consumer Safety Officers (CSOs) look at first.  The regulatory binder is a road map of what happened during the clinical trial.  The IRB approvals, FDA approval documentation, and protocol versions are reviewed and recorded for the report.  The monitor reports and frequency of visits directly corresponds to the amount of observations FDA CSOs finds. So far, so good.

The areas most scrutinized for review are the protocol deviations & violations and adverse event reporting.  If a serious adverse event was not reported or not reported per protocol, you’d better expect a 483.  Failure to follow the IRB approved protocol version is the most cited 483 observation.

How does this keep happening over and over again? Easy: research clinic turn-over, lack of training on updated protocol or study procedures and the lack of monitoring.  The FDA is now requiring 100% consent form review of all subjects.  Failure to obtain informed consent with IRB approved document is the second most cited 483 item.

The third and most documented for clinical research 483 items is lack of complete or inaccurate source documentation.  The FDA is now requesting CSOs to audit the firm electronic systems and record any deficiencies on a 483.  The electronic records evolution started in 1999 and the FDA is now catching up and training CSOs to find your Part 11 computer system shortfalls and deficiencies.  Here, the FDA is turning to the ICH model as a bridge to the European Medicines Agency counterpart inspectorate.

The EMA model requires third party QA for every research trial which has proven to cut down on regulatory deficiencies.  In my opinion having that third set of QA eyes is all the difference between no action indicated (NAI) &  voluntary action indicated (VAI) from official action indicated (OAI) and a project hold.

Editor’s note: This is the the first in a series from our new blogger, Patrick Stone, M.S.  Patrick left the FDA in March 2011 after 12 years as a Biosresearch monitor at the agency’s Austin, TX office. He’s now President of TradeStone QA. While with the FDA, Patrick conducted domestic and international inspections of clinical investigators for pre-approval of pharmaceutical drugs, pharmaceutical drug manufacturing plants and domestic Institutional Review Board investigations.

As Stone recently told us, “I have worked closely with all departments (except foods CFSAN) CDER CBER CDRH and CVM. My work has gone through all of those department heads, too. I have 13 warning letters, one NDA revocation, and countless 483’s. I completed on average of 24 BIMO (clinical trial) audits every year since 2001 when I started conducting audits solo. It is my hope to bring some of that experience to readers of this blog.”

You can follow Patrick on Twitter: http://twitter.com/BIMOQA


  • Reply

    Thank you Patrick for sharing your FDA and 483’s experience.and knowledge. I found this article quite useful and interesting.

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