FDA took on the largest pharmaceutical company in the world, Pfizer, after FDA documented that as many as 13 children were overdosed with the drug Geodon, being studied to treat bipolar disorder. In a one month inspection an FDA field investigator, accompanied by a physician from the Center for Drugs, Division of Scientific Investigations (DSI), reviewed Pfizer’s conduct. It took FDA 11 months to write the Warning Letter, dated April 13, a delay that would not have been permitted a few years ago. However, in the past three years FDA has cited three of the largest pharmaceutical companies for failures as a sponsor of clinical trials.
All three were cited for the failure to monitor the progress of the investigation, an activity that is more likely than not contracted out to CROs- Contract Research Organizations. The other two large sponsors, Sanofi-Aventis and Johnson & Johnson, used CROs to monitor their studies. It is not clear from the Warning Letter if Pfizer used a CRO for the audited studies. There were other dosing errors of concern to FDA in the Warning Letter. Pfizer was also cited for informed consent issues and failure to have cardiologists available to read safety ECGs.
FDA had this to say about Pfizer’s conduct on monitoring:
“FDA regulations require that sponsors ensure proper monitoring of clinical investigations. Our investigation found that Pfizer failed to properly ensure monitoring of the study referenced above. As a result of inadequate monitoring, widespread overdosing of study subjects at multiple study sites was neither detected nor corrected in timely manner.”
Pfizer responded to FDA as reported by the Associated Press, in an article by Matthew Perrone.
Pfizer spokeswoman Kristen Neese said many of the problems cited by the FDA were first pointed out by the company itself more than four years ago.
‘Pfizer has communicated with the FDA about our conduct of clinical trials and, over the next two weeks, will provide an outline of new and existing processes for preventing similar issues with Pfizer clinical trials,’ Neese said in a statement.”
It is important to note that FDA had cited Pfizer in the past regarding the failure to monitor clinical trials. Repeat violations are more likely to result in an enforcement action. However, all three of these sponsor Warning Letters indicate that if something goes wrong at a clinical site, such as overdosing children, then the sponsor will be held responsible.
In Pfizer’s defense, it should be noted that Pfizer is the organization that caught the overdosing. The Warning Letter cites Pfizer for not determining that the subjects received incorrect dosages of study drug through their monitoring of the site. However, Pfizer data managers determined the overdose occurred. It seems that Pfizer may have been “monitoring the progress of the investigation” in more than one way, through monitoring visits AND through review of the data by their data management department. It seems harsh to me to cite a sponsor for violations that the sponsor found themselves. Something to think about.
This is the first Warning Letter that Pfizer has received for clinical or other research. They have received Warning Letters in the past for labeling or promotional claims, most recently in 2008.