Glioblastoma multiforme with an unusual location and clinical course.

We present a unique case of a brain tumor patient with atypical location and progression. He was initially presented with mood and anxiety type symptoms together with aphasia and left-sided paraesthesias. Magnetic resonance imaging and CSF were negative and the patient was diagnosed with PTSD as he recently experienced a small motor vehicle accident. Two months after the first presentation, MRI revealed multifocal juxtacortical, leptomeningeal hyperdensities in the bilateral frontal lobes. MRI-guided frameless stereotactic biopsy defined a diagnosis of GBM 1 week prior to death which occurred within 4 months. Postmortally, formalin-fixed brain demonstrated that the main tumor mass was located in the fornix, infiltrating the ventricular system and disseminating over the cortex, cerebellum and spinal cord. The authors recommend closer scrutiny of psychiatric patients presenting CNS symptomatology, negative MRI, CT and CSF.

Safety of laboratory analyzers for infection testing - results of the market surveillance by the BfArM until End 2007.

The European Directive 98/79/EC on in vitro diagnostic medical devices (IVD) stipulates the marketing and post market surveillance of IVD in the European Economic Area. In cases of issues 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, with a small subset of IVD for immune hematological and infectiological testing as well as tissue typing as specified in Annex II of the Directive, being within the responsibility of the Paul-Ehrlich-Institute (PEI). In this study, all issues regarding laboratory analyzers for infection testing and their consumables, but not reagents, kits and general culture media, reported to the BfArM between begin 1999 and end of 2007 were analyzed in respect to the sources of report, the underlying product failure and the performed corrective actions. Within the observation period a total of 1471 reports for IVD were received of which 73 related to the IVD for infection testing were included in our study. Reports were predominantly received from manufacturers (56) and competent authorities (15). Affected products were most frequently those for immunological analysis (42) whereas those based on culturing techniques (17) and molecular biological techniques (14) played only minor roles. In all these groups, laboratory analyzers (55) were more frequently affected than their consumables (18). Investigations of the manufacturers were able to identify the underlying root causes of product failures in 62 cases (84.9%). In 2 cases (2.7%) the root cause remained unclear and in 9 cases (12.3%) a product failure was excluded or a user error was the underlying cause. Product failures in laboratory analyzers were most frequently caused by software errors (31) and constructional faults (8) whereas the predominant cause of product failure in consumables were errors in production and quality control (8). Manufacturers issued corrective measures in 66 cases (90.4%) from which 49 and 17 were related to laboratory analyzers and their consumables, respectively. Based on the underlying root causes of product failures these were predominantly customer information (48), recalls (40), software-updates (30) and design changes (9) in the product group of laboratory analyzers as well as customer information (16), recalls (12) and modifications of production and quality management (11) in the group of consumables. The results and experiences obtained since 1999 suggest that the system for post marketing surveillance of IVD is an established tool to ensure product safety, even though the current system can be further enhanced.

[Safety of high risk in vitro diagnostic medical devices : international and national measures]. / Die Sicherheit von Hochrisiko-in-vitro-Diagnostika : Internationale und nationale Massnahmen.

The European Directive 98/79/EC for in vitro diagnostic medical devices (IVD) [1] regulates the marketing and post marketing surveillance of IVD in the European Union. In accordance with this regulation, those legally responsible for the IVD product have to report all incidents and corrective measures with IVD to the national competent authority. In Germany, these are the Federal Institute for Drugs and Medical Devices (BfArM) and for high risk products, as specified in Annex II of the Directive 98/79/EC, the Paul Ehrlich Institute (PEI). From 2002 to 2007, PEI registered 204 reports concerning incidents with and recalls of IVD medical devices. The majority of incident reports (84.4%) were sent by IVD manufacturers to the PEI. The reporting ratio of the IVD users amounted to 8.5%; in 12 cases (7.1%) PEI was informed via Vigilance Reports from other European competent authorities concerning incidents and recalls with IVD. The experience from 6 years' IVD surveillance showed that the German market surveillance system ensures a high level of safety concerning the in vitro diagnostic medical devices of Annex II list A and B of Directive 98/79/EC. However, the current system can be further optimized.

Safety of reagents for infection testing: results of the market surveillance by the Federal Institute for Drugs and Medicinal Devices until end 2006.

The European Directive 98/79/EC on in vitro diagnostic medical devices (IVD) stipulates the marketing and post market surveillance of IVD in the European Economic Area. In cases of issues 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, with a small subset of IVD for immune hematological and infection testing as well as tissue typing as specified in Annex II of the Directive, being within the responsibility of the Paul-Ehrlich-Institute (PEI). In this study, all issues regarding reagents for infection testing, but not laboratory analyzers, reported to the BfArM between begin 1999 and end of 2006 were analyzed in respect to the source of report, the underlying product defects, and the performed corrective actions. Within the observation period a total of 888 reports on IVD were received of which 90 related to the IVD for infection testing included in our study. Reports were predominantly received from manufacturers (55) and Competent Authorities (29). Affected products were most frequently those for serological analysis (42) and culturing techniques (36), whereas molecular biological tests played only a minor role (12). Investigations of the manufacturers were able to identify the underlying root causes of product failures in 68 cases (75.6%). In 16 cases (17.8%) the root cause remained unclear and in 6 cases (6.6%) a product failure was excluded or a user error was the underlying cause. Most frequently product failures were caused by material defects (25), production errors (11), microbial contamination (6), and labelling errors (5). Manufacturers issued corrective measures in 73 cases (81.1%). Based on the underlying root causes of product failures, these were predominantly (multiple entries) customer information (71), recall (58), modifications in production or quality management (50), modifications of the raw materials (17), and modifications of the instructions for use (12). The results and experience obtained since 1999 suggest that the system for post marketing surveillance of IVD is an established tool to ensure product safety even though the current system can be further optimised.

[Safety of in-vitro diagnostics used in transfusion medicine. Experience of the BfArM until end 2005]. / Sicherheit von In-vitro-Diagnostika zum Gebrauch in der Transfusionsmedizin. Erfahrungen des BfArM bis Ende 2005.

The European Directive 98/79/EC on in-vitro diagnostic medical devices (IVD) stipulates the marketing and post marketing surveillance of IVD in the European Economic Area. In cases of incidents and field corrective actions related to IVD, manufacturers have to inform the responsible Competent Authorities. In Germany, the Federal Institute for Drugs and Medical Devices (BfArM) is the responsible Competent Authority for most IVD. Only a small subset of IVD for immune hematological and infectiological testing, as well as tissue typing specified in Annex II of the Directive, is under the responsibility of the Paul-Ehrlich-Institute (PEI). Until the end of 2005 the BfArM received a total of 653 notifications regarding IVD. From these 48 related to IVD used for diagnostics in transfusion medicine and tissue typing which are subject of this study. The investigated products included reagents (tests, calibrators and controls) used for immune hematological analysis as far as they are not under the responsibility of the PEI, analyzing instruments used for immune hematological testing, liquid handling systems for sample preparation and a small subset of analysing instruments and reagents for tissue typing. Most of the reports originated from manufacturers (n=27, 56.3%) and Competent Authorities (n=20; 41.7%) whereas other sources played only minor roles. Product failures were confirmed by the investigations of the manufacturers in 36 (75%) of the reported incidents. Reagents were frequently subject of manufacturing errors and biological contaminations, whereas analysing instruments were typically affected by software errors. In consequence, corrective actions were performed in the large majority of cases (n=37; 77.1%). These included customer information, product recalls, changes in production or quality management and software upgrades (the latter predominantly in cases of failures of analysing instruments). Our data suggest that the governmental system for marketing surveillance is an established tool to ensure product safety for IVD used in transfusion medicine.