If you are in the medical device industry, either as an inventor, developer, or manufacturer, and you are planning to market in the US, reviewing FDA warning letters should be part of your weekly if not daily routine. You will find out how your competitors or subcontractors are doing but more importantly you will find out what is the focus of the Agency’s inspections. Another benefit of being informed is the opportunity to improve your Quality Management System (QMS) before the FDA knocks on your door.

From December 2011 to February 21, 2012, the Agency issued 30 warning letters to medical device companies; 5 were related to the same product being advertized off the label. Noted violations range from complete absence of QMS to deficiencies in either content or implementation of the procedures. The Top 10 violations are listed below. Approximately half of the inspected companies had violations in design control, record keeping, complaint and CAPA handling, lacking adequate Medical Device Reporting (MDR) and document control procedures. The other warning letters had variety of violations of the Quality System Regulation (QSRs) usually accompanied by lack of evidence of implemented changes and training of personnel.

Table 1 – Top 10 Violations

	Area of non-compliance	Total # of observations
1	Design change control, design verification and validation	16
2	General record keeping, DMR, DHR or DHF	15
3	Complaints	15
4	MDR	14
5	QMS, document control, approval and effective date	14
6	CAPA	13
7	Incoming inspections and purchasing controls	12
8	Advertizing/off the label use	9
9	Premarket approval	9
10	Finished device inspection criteria	8

Overall, the trends in warning letters and recalls continue to signal a robust enforcement approach by FDA. It is reasonable to anticipate that this trend will continue as the Agency continues to focus on preventive controls and taking regulatory action more than in the past.

The consequences of getting warning letters can be very serious. In the worst-case scenario, FDA can shut down US facilities while for foreign companies, FDA can issue an import alert to prevent products from entering the US market.

The response outlining corrective actions or plan must be sent within 15 days of issuance of the FDA’s 483 form. For violations such as promotional activities, corrective actions could be simple and fast. For other violations, depending on their severity, it is not unreasonable to estimate that months of labor may be spent on corrective actions. Finally, beside damaged reputation, medical device companies suffer business implications as some of your key personnel may be engaged in ‘closing’ the warning letter for months instead of working on projects.