Market surveillance of in vitro diagnostics by the BfArM until end 2010: safety of IVD for therapeutic drug monitoring.

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 for therapeutic drug monitoring (TDM) between begin 1999 until end of 2010 were analysed. A total of 2,851 notifications were received, of which 65 were related to IVD for TDM included in this study (54 tests vs. 11 analysers). Reports were received from manufacturers (58), CAs (5 cases) and users (2 cases). Most frequently IVD used for TDM of toxicologically relevant substances, antibiotics, antiepileptics and immunosuppressives were affected. Investigations of the manufacturers were able to identify the underlying root causes of product failures in 50 cases (76.9%), 40 (74.1%) of which were tests and 10 (90.9%) analysers. In 11 cases (16.9%, all tests), the root cause remained unclear and in 4 cases (6.2%, 3 tests, 1 analyser) a product failure was excluded. Product failures in tests were most commonly material defects (12 cases), interferences (7 cases) and manufacturing errors (7 cases), whereas in the analyser group software errors (5 cases) were most common. Corrective actions were performed in 56 cases (86.2%); 46 (85.2%) in tests, and 10 (90.9%) in analysers. In the group of tests these were predominantly (multiple entries) customer information (46 cases, mandatory in case of a recall), recall (29 cases), modifications in production or quality management (29 cases) and modifications of the instructions for use (9 cases). However, in the analyser group corrective actions were typically customer information (10 cases), recall (5 cases) and software-update (4 cases). The obtained data demonstrate that there are differences in the type of product failures between analysers and tests, which are followed by different corrective actions depending on the root causes of product failure accordingly. The results and the experience since 1999 suggest that the system for post marketing surveillance of IVD is an established tool to enhance product safety even though further optimisation is possible.