Johnson and Johnson received a Warning Letter from FDA for their failure to properly supervise clinical trials. The letter, issued by the Center for Drug Evaluation and Research’s Division of Scientific Investigations (DSI) on 10 August 2009, was addressed to the J&J Pharmaceutical Research & Development group in Raritan, NJ and cited failures for sponsor responsibilities.
It is pretty rare for a pharmaceutical company to get a Warning Letter for clinical trial sponsor activities (called “Sponsor-Monitor” inspections). Approximately 10 were issued in fiscal year 2008 and most of those were to small medical device firms or to sponsor-investigators, physicians who both sponsor and conduct a clinical trial. The last major Warning Letter to a large pharmaceutical company was to Sanofi Aventis in October 2007 for research misconduct in the Aventis clinical trials for the drug Ketek. So DSI sending a Warning Letter to an industry giant like J&J is a pretty big deal. It certainly is in keeping with Commissioner Margaret Hamburg’s new emphasis on enforcement (see previous posts).
The Warning Letter cites J&J for “Failure to ensure proper monitoring of the clinical investigations.” This is the most common citation for a Sponsor-Monitor Warning Letter and has been for many years. DSI charges that J&J’s monitors failed to identify that drug infusions were given at the same identical time to multiple subjects. The drug is administered by an IV infusion and the source documents were contradictory and should have alerted the monitors of possible fraud. The Warning Letter cites detailed violations for study drug administration, shipments, and the necessary refrigerated storage.
The lengthy Warning Letter also cites J&J for “Failure to ensure that an investigation was conducted in accordance with the general investigational plan and protocols” and “Failure to secure investigator compliance.” These are also common violations for a Sponsor-Monitor Warning Letter. You can read the letter for yourself on the Blogroll: 1 FDA Warning Letter to J&J.
It will be interesting to see if the new enforcement climate will deal new Warning Letters to pharmaceutical and medical device sponsors or if this was an aberration. The one thing that it has in common with the Sanofi Aventis Warning Letter is that there is a suggestion of fraud. There are many things other than fraud that can go wrong in a clinical trial. Is this FDA’s standard?
I am attaching an article that I wrote for RAPS Regulatory Focus magazine in July 2008. It deals with the topic of quality systems in monitoring clinical trials.