FDA Warning Letter Overview 2002 - 2006

This page is intended to give readers some sense of FDA activity and oversight of clinical research in terms of warning letters issued to clinical investigators, institutional review boards (IRBs), and sponsors, monitors, and contract research organizations (CROs). Clinical investigators are researchers who conduct drug and medical device research (= clinical trial, study) at study sites, such as hospitals, universities, clinics, physician offices, and other locations in the community. Institutional review boards (IRBs) are the entities responsible for protecting the rights and welfare of research subjects. IRBs fulfill this responsibility by review and approval of proposed research and by continuing review of ongoing research. Sponsors, like drug and medical device manufacturers, are entities that cause research to be conducted. In addition to being charged with overall responsibility for the conduct of research, sponsors have a number of specific obligations, one of which is the monitoring of ongoing research. To fulfill this obligation sponsors rely on monitors, individuals who audit (or check) data and records at study sites. Contract research organizations (CROs) are commercial entities that perform some or all activities in clinical trials. Depending upon services offered and client need, CROs could conduct a large multi-site study from start to finish or provide a single service, such as recruitment. A sponsor also has the option to transfer their obligations to a CRO.

Warning letters are only one indication of FDA activity and oversight of clinical research. FDA oversees drug and medical device research to a certain extent during review of Investigational New Drug (IND) and Investigational Device Exemption (IDE) applications. In the case of IND applications for clinical trials with drugs, FDA has 30 days in which to object to, or require revision of, proposed research. IDE applications for medical device studies require explicit FDA approval. This oversight is limited by its focus on study design, and as limited as it is, it only applies to clinical trials conducted under IND and IDE applications. Not all clinical trials are conducted under IND and IDE applications. FDA does not monitor or oversee clinical trials while they're underway. FDA has the option, however, to conduct for cause inspections if the agency thinks there may be a serious problem. In principle this is great but it may or may not work out well in practice. The most obvious limitation on the utility of inspection for cause is reporting. Put differently, FDA can't inspect what it doesn't know about. Responsibilities for reporting serious adverse events (SAEs), unanticipated problems, or suspected misconduct are divided among the sponsor, the clinical investigator, and the IRB, and the extent to which problems are reported to FDA in a timely and accurate way depends upon a number of factors including training and experience and professional judgment. As a rule, it's often difficult for members of the public to complain to FDA about research. Lack of staff and adequate funding impose further limitation if and when FDA can only inspect those studies in which problems appear to be the most serious. FDA also routinely inspects a small subset of study sites prior to approving drug and device marketing applications. These inspections (called drug audit inspections) are of little or no use in protecting research subjects because the focus is primarily on data integrity and they often take place long after, or even years after research is finished. Keeping these limitations in mind, FDA warning letters can provide useful information. We intend to add more tables and refine existing ones as time permits.

What is an FDA Warning Letter?

A Warning Letter is an informal advisory, to a firm or clinical investigator, communicating the Agency's position on a matter but does not commit FDA to taking enforcement action. A Warning Letter is issued for significant regulatory violations that require prompt and adequate corrective actions.
Source: FDA Center for Drug Evaluation and Research, Division of Scientific Investigations. Accessed 2006-03-19 from http://www.fda.gov/cder/Offices/DSI/enforcement.htm

FDA Warning Letters To Clinical Investigators 2002-2006

Year	Number of FDA Warning Letters to Clinical Investigators
2002	13
2003	20
2004	32
2005	30
2006	22

Source: U.S. Food and Drug Administration Warning Letter Search by Date and Export to Excel. Accessed on 2007-03-31 at: http://www.accessdata.fda.gov/scripts/wlcfm/export_report_excel.cfm

CDRH: Center for Devices and Radiological Health re: objecionable conduct in research testing a medical device.
CDER: Center for Drug Evaluation and Research re: objectionable conduct in research testing a drug.
CBER: Center for Biologic Evaluation and Research re: objectionable conduct in research testing a biologic.

FDA Warning Letters To Institutional Review Boards 2002-2006

Year	Number of FDA Warning Letters Issued	CDRH	CBER	CDER
2002	5	3	2	0
2003	8	7	1	0
2004	6	6	0	0
2005	4	3	1	0
2006	7	3	2	2

Source: U.S. Food and Drug Administration Warning Letter Search by Date and Export to Excel. Accessed on 2007-03-31 at: http://www.accessdata.fda.gov/scripts/wlcfm/export_report_excel.cfm

FDA Warning Letters To Sponsors, Monitors, and Contract Research Organizations (CROs) 2002-2006

Year	Number of FDA Warning Letters Issued	CDRH	CBER	CDER
2002	1	0	0	1
2003	9	9	0	0
2004	10	8	0	2
2005	10	10	0	0
2006	6	5	0	1

Source: U.S. Food and Drug Administration Warning Letter Search by Date and Export to Excel. Accessed on 2007-03-31 at: http://www.accessdata.fda.gov/scripts/wlcfm/export_report_excel.cfm

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Last Updated: 2007-08-01

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