by Michael A. Trapani, MS, MBA, Senior Consultant

In our last edition of the Biologics Consulting Group's Bulletin, Senior Consultant, John Godshalk, analyzed the types of warning letters issued by FDA during 2006. John notes that the three FDA Centers (Human Drugs, Biologic and Medical Devices) issued letters to firms and that most of the letters were issued for GMP and QSR non-compliance. In this article, we've assessed FDA warning letters related to Good Clinical Practices that were issued to sponsors of human clinical trials during the period of 2002 through 2006. In future reviews, we will take a closer look at warning letters issued to IRBs and Clinical Investigators.

During the past five years, FDA issued twenty-nine (29) warning letters to sponsors of human clinical trials. Of these, CDRH issued the majority, twenty-four (24), whereas CBER issued four and CDER issued one. See Chart below.

Of the FDA warning letters issued by CBER and CDER the following compliance issues were noted:

• Failure to ensure proper monitoring of the clinical study
  
• Failure to use staff qualified by training and experience
  
• Failure to inform FDA of significant information about the study
  
• Failure to control the shipment of investigational products only to Clinical Investigators authorized to receive them
  
• Failure to maintain adequate records for shipping and accountability of investigational products

Since the majority of the Warning Letters were issued by CDRH, a closer examination of compliance issues related to investigational medical devices was conducted. This examination uncovered that essentially all (22/24) warning letters issued during the past five years by CDRH cited the failure to adequately monitor clinical studies. Other common compliance issues cited include:

• Failure to use monitoring staff qualified by training and experience
  
• Failure to have written monitoring plans
  
• Failure to secure compliance of Clinical Investigators who have not complied with the investigational plan and/or other applicable regulations or take the appropriate actions to terminate the Investigator's participation in the study
  
• Failure to control shipments of investigational devices only to Investigators authorized to receive them
  
• Failure to inform FDA and/or IRBs of significant information about the study

The information cited above demonstrates consistency within the three FDA Centers regarding the types of compliance issues of importance to FDA. The information also suggests that Sponsors need to improve their internal processes and systems for monitoring clinical studies.

BCG has qualified consultants who can assess a Sponsor's GCP program and provide recommendations for improvement. With the cost of bringing a new medicine to market estimated to be greater than $800 million, can any Sponsor afford the cost of repeating a study because of GCP compliance issues? We are here to assist you.

For additional information, please contact Michael A. Trapani, MS, MBA

Page Updated August 21, 2008