Market surveillance of in vitro diagnostics by the BfArM until end 2010: how safe are products for tumor diagnostics?

The European Directive 98/79/EC on in vitro diagnostic medical devices (IVD) regulates the marketing and post market surveillance of IVD in the European Economic Area. In cases of incidents and field corrective actions the manufacturers have to inform the responsible Competent Authorities (CA). In Germany, the Federal Institute for Drugs and Medical Devices (BfArM) is the responsible CA for most IVD. In this study all notifications regarding IVD (tests, calibrators, kits, and control materials, except laboratory analyzers) for tumor diagnostics received by the BfArM between begin 1999 until end of 2010 were analyzed. All notifications were analyzed in respect to the type of product, the source of notification, the underlying product defects and the corrective actions performed. In the observation period, a total of 2,851 notifications were received of which 84 were related to IVD for tumor diagnostics included in this study (clinical chemistry - 63, histology - 6, molecular biology - 3, rapid tests - 12). Reports were received from manufacturers (68 cases), CA (8 cases), users (4 cases) and other sources (4 cases). In the group of IVD based on clinical chemistry means, the affected products were mostly those for the measurement of prostate specific antigen (PSA, 14 cases), human chorion gonadotropine (13 cases), carcino embryonic antigen (6 cases), CA 19-9 (6 cases), α(1)-fetoprotein (6 cases) and CA 125 (5 cases), whereas in test strips 9 out of the 12 notifications were related to PSA. Investigations of the manufacturers were able to identify the underlying root causes of product failures in 66 cases (78.6%). In 10 cases (11.9%) the root cause remained unclear and in 6 cases and 2 cases (7.1% and 2.4%) a product failure was excluded or a user error was the underlying cause. Most common root causes of product failures were material defects (24 cases) and manufacturing errors (15 cases). Corrective actions were performed by the manufacturers in 64 cases (76.2%) and were predominantly (multiple entries possible) customer information (62 cases, mandatory in case of a recall), recalls (45 cases), modifications in production or quality management (45 cases) and design changes (14 cases). The obtained results suggest that the system for post marketing surveillance of IVD is an established tool to enhance product safety and provides valuable information on product specific problems serving for improvement of product safety.