For the first time since 2002, Device History Records and Nonconforming Product were among the top five FDA Warning Letter citations in 2012, according to the European Compliance Academy (ECA), which bases its analysis on the fiscal calendar. We also saw an overall increase of sixteen-percent in Warning Letters from 156 issued in 2011 to 181 issued in 2012. In 2010, the Center for Devices and Radiological Health (CDRH) issued 182 Warning Letters, citing Corrective and Preventive Actions and Complaint Records most, followed by Design Control, Process Validation, Receiving, in-process, and finished device acceptance, and Management Responsibility respectively.
The purpose of a Warning Letter, according to FDA is to ensure that the seriousness and scope of the violations are understood by top management, and that the appropriate resources are allocated to fully correct the violations and prevent their recurrence.
Historically, 21 CFR 820.100 Corrective and Preventive Action is cited most in Warning Letters issued by CDRH. According to ECA, only once in the last 10 years has another section of the Quality System Regulation been cited in Warning Letters issued by CDRH more than CAPA. Fifty-seven-percent of the Warning Letters issued in 2007 contained citations for Design Control deficiencies. Nearly 30% of the Design Control violations were in the areas of verification and validation, while nearly 12% cited violations in Design Changes.
The number of warning letters issued by CDRH has increased significantly since mid-2009, when FDA announced that it would no longer require the Agency’s Office of Chief Counsel to review letters for legal sufficiency except in cases involving “significant legal issues.” The goal of the new policy was to increase enforcement and to limit enforcement delays, and the results were staggering. Industry was, for a lack of a better word, alarmed by an increase in Warning Letters issued by CDRH of 117% from 84 Warning Letters in 2009 to 182 Warning Letters in 2010.
In the ten year period between 2002 through 2012, CDRH issued an average of 83 Warning Letters through 2009. Since 2010, CDRH has issued an average of 173 Warning Letters per year to medical device manufacturers. The Agency’s goal is to prioritize follow-up on all Warning Letters and other enforcement actions, working quickly to assess corrective action taken by the manufacturer. As part of its commitment, FDA introduced its formal Warning Letter close-out process. If the Agency determines that a manufacturer fully corrected the violations, it will issue an official close-out notice, and post it to the FDA website.
Among the common violations cited in Warning Letters, a new trend developed in nonconforming product and Device History Record violations in 2012. Medical device manufacturers were cited for failure to establish and maintain adequate procedures, and identify and adequately investigate the root cause of nonconforming product. Among the citations, manufacturers failed to establish and maintain adequate procedures for rework, retest and reevaluation of nonconforming product, and maintain adequate Device History Records.
Ten Warning Letters issued by CDRH have been posted to the FDA Warning Letter database online since January 1, 2013. Half of the Warning Letters issued so far this year cite Medical Device Reporting violations, six cite Quality System Regulation violations, one cites misleading promotion and advertising, and one cites a lack of clearance or approval to market the device.
Quality System Regulation violations in published Warning Letters issued by CDRH this year are summarized in the table below. So far this year, 13 Design Control violations, 13 Records violations, 10 Production and Acceptance violations, eight CAPA and Internal Audit violations, and three Nonconforming Product violations are cited in the top five areas of the quality management system.
|820.80||Receiving, In-Process, and Finished Device Acceptance||5|
|820.70||Production and Process Controls||5|
|820.181||Device Master Record||4|
|820.184||Device History Record||3|
|820.72||Inspection, Measuring, and Test Equipment||1|
|*Five Warning Letters also cite Part 803 violations|
A greater focus this year should be directed toward Design Control, Records, Production and Process Controls, Acceptance Activities (including Nonconforming Product) and Internal Audit.