Product Failures in Respirators and Consumables: Analysis of Field Safety Notices of 2005-2013 Publicized by the Federal Institute for Drugs and Medical Devices in Germany.

The current European system governed by the three EC directives 93/42/EEC (Medical Device Directive), 98/79/EC (In-Vitro Diagnostic Directive) and 90/385/EEC (Active Implantable Medical Device Directive) regulates marketing and post-market surveillance of medical devices in the European Economic Area (EEA). In cases of incidents raising the field safety corrective actions (FSCA), manufacturers have to inform the responsible Competent Authority (CA; in Germany this is the Federal Institute for Drugs and Medical Devices, BfArM) and the public by field safety notices (FSN). In this study we analyzed FSN of respirators and consumables directly required for their function, whereas devices for anesthesia and gas delivery were excluded. FSCA and FSN of 2005-2013 publicized by BfArM for the included products were analyzed with respect to the MEDDEV 2.12-1 rev. 8. In total, 60 FSCA were publicized. German and English FSN were found in 59/53 cases, respectively. FSN were clearly characterized as FSN in 44/38 cases and declaration of the type of action in 45/44 cases, respectively. Product names were provided in all cases. Lot numbers or other information for product characterization were available in 7/7 and 43/40 cases, respectively. Detailed information regarding FSCA and product malfunction was found in all cases. Information on product related risks with previous use of affected devices was provided in 42/38 cases. In 53/53 cases manufacturers provided information to mitigate product related risks. Requests to pass FSN to persons needing awareness in the organization were found in 27/24 cases. Contact data were provided in 53/48 cases, respectively. Confirmation that a CA was informed was found in 28/26 cases and in 19/15 cases a customer confirmation was included. The identified risks were: total loss of function (19/16), short circuit (1/1) and burn (3/3), and inhalation of foreign particles (1/1) which might cause severe risk to patients and users. The most frequent FSCA were product modifications and customer information. The data suggest that there is an annually increasing number of FSCA on devices included in our study. Most FSN fulfill the criteria of MEDDEV 2.12-1 rev. 8. However, there are differences between German and English FSN, e.g., regarding the distribution to persons needing awareness, missing statement that a CA was informed, and missing customer confirmation. Due to the importance of FSN for reduction of product related risks in FSCA, the type and content of FSN should be further improved.

Field Safety Notes in Product Problems of Medical Devices for Use in Pulmonology.

The current European system for medical devices is governed by three EC directives: the Medical Device Directive 93/42/EEC, the In-Vitro Diagnostic Directive 98/79/EC and the Active Implantable Medical Device Directive 90/385/EEC and regulates marketing and post-market surveillance of medical devices in the European Economic Area. In cases of incidents and field safety corrective actions (FSCA) manufacturers have to inform the responsible Competent Authority, which is the Federal Institute for Drugs and Medical Devices (BfArM) and the public by field safety notices (FSN). In this study we analyzed FSN of medical devices exclusively serving for diagnostics or treatment in pulmonology (e.g. nebulizers, oxygen concentrators, pulse oximeters, lung function analyzers, and non-active devices for treatment). FSCA and FSN publicized by BfArM in 2005-2013 were analyzed in respect to the MEDDEV 2.12-1 rev 8. In total 41 FSCA were publicized for the included products. German and English FSN were found in 36/35 cases, respectively. FSN were clearly characterized as FSN in 22/20 cases and declaration of the type of action was found in 27/26 cases, respectively. Product names were provided in all cases. Lot numbers or other information for product characterization were available in 7/8 and 26/24 cases, respectively. Detailed information regarding FSCA and product malfunction were found in 27/33 and 36/35 cases, respectively. Information on product related risks with previous use of the affected product was provided in 24/23 cases. In 34/34 cases manufacturers provided information to mitigate product related risks. Requests to pass FSN to persons needing awareness were found in 10/14 cases. Contact data were provided in 30/30 cases. Confirmation that the Competent Authority was informed was found in 12/14 cases and in 19/18 cases a customer confirmation was included. The obtained data suggest that there is an increasing annual number of FSCA and most FSN fulfill the criteria of MEDDEV 2.12-1 rev 8. However, there are differences between German and English FSN, e.g. regarding the distribution to persons needing awareness, missing statement that the Competent Authority was informed and missing customer confirmation. Due to the importance of FSN for reduction of product related risks in FSCA type and content of FSN should be further improved.

Does customer information fulfill MEDDEV criteria in cases of product problems of in vitro diagnostics for infection testing?

The European Directive 98/79/EC on in vitro diagnostics (IVD) regulates marketing and post market surveillance of IVD in the European Economic Area. In cases of incidents and field safety corrective actions (FSCA) manufacturers have to inform responsible competent authority (CA) and public by field safety notices (FSN). We analyzed FSCA and FSN of IVD for infection testing (culture media, reagents, kits, control materials, as well as culture-based analyzers and their general consumables) published by the Federal Institute for Drugs and Medical Devices (BfArM) in Bonn, Germany in 2005-2012 in regard to the European Regulatory Framework of Medical Devices (MEDDEV). One hundred and sixty-nine FSCA were published and German and English FSN were found in 157 and 154 cases, respectively. FSN were clearly characterized as FSN in 110 German and 134 English cases and product names were provided in 157 and 154 cases, respectively. Lot numbers and other information for product characterization were available in 146 and 137 cases, respectively. The information regarding FSCA and product malfunction was provided in 157 and 151 and 144 and 136 cases and that regarding the product related risks with continued use of affected IVD in 116 and 116 cases, respectively. In 156 German and 152 English cases, manufacturers provided the information for risk mitigation, including retesting in 69 and 75 cases, respectively. Requests to pass FSN to persons needing awareness were found in 108 and 87 cases, and contact data were provided in 127 and 131 cases, respectively. We conclude that most FSN fulfilled the MEDDEV criteria. However, type and content of FSN should be improved to ensure a better mitigation of risks due to product failure.

Poloxamer 188 prevents acute necrosis of adult skeletal muscle cells following high-dose irradiation.

Acute cellular necrosis occurring minutes to hours after massive ionizing radiation exposure (IR) results from rapid membrane lipid peroxidation, blebbing and membrane breakdown. We have shown, previously, that certain polymer surfactants can restore structural integrity and transport barrier function of cell membranes following high-dose IR. We now investigate, specifically, the efficacy of the amphiphilic surfactant Poloxamer 188 (P188) in preventing acute necrosis of adult rat skeletal muscle cells after high-dose IR. Explanted cells were treated with 60Co IR doses of 10, 40 or 80Gy and their viability was determined using fluorometric probes at 4 and 18h post-IR. IR of 10Gy did not cause acute necrosis. Significant acute cell necrosis was observed after 40 and 80Gy doses in a dose-dependent manner. Post-IR treatment with P188 significantly enhanced the cells' viability post-IR treatment. By comparison 10kDa neutral dextran, a hydrophilic polymer, was found to be ineffective. Despite progressive cell death over 18h after high-dose IR, cells treated with P188 manifested greater survival than media or dextran-treated cells. It appears that use of P188 or similar multi-block copolymers to prolong viability of irradiated cells in vitro through membrane sealing is an important step in development of effective interventional therapy for extreme IR exposure. Not only can repairing the membrane prevent acute necrosis, but it also can provide a critical time opportunity to address other mechanisms of cell death, such as apoptosis or mitotic arrest, which manifest over a longer time frame.

Direct observation of poloxamer 188 insertion into lipid monolayers.

P188, a triblock copolymer of the form poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) helps seal electroporated cell membranes, arresting the leakage of intracellular materials from the damaged cells. To explore the nature of the interaction between P188 and cell membranes, we have constructed a model system that assesses the ability of P188 to insert into lipid monolayers. Using concurrent Langmuir isotherm and fluorescence microscopy measurements, we find that P188 changes the phase behavior and morphology of the monolayers. P188 inserts into both dipalmitoylphosphatidlycholine and dipalmitoylphosphatidylglycerol monolayers at surface pressures equal to and lower than approximately 22 mN/m at 30 degrees C; this pressure corresponds to the maximal surface pressure attained by P188 on a pure water subphase. Similar results for the two phospholipids indicate that P188 insertion is not influenced by headgroup electrostatics. Because the equivalent surface pressure of a normal bilayer is on the order of 30 mN/m, the lack of P188 insertion above 22 mN/m further suggests the poloxamer selectively adsorbs into damaged portions of electroporated membranes, thereby localizing its effect. P188 is also found to be "squeezed out" of the monolayers at high surface pressures, suggesting a mechanism for the cell to be rid of the poloxamer when the membrane is restored.

Blood extraction from lancet wounds using vacuum combined with skin stretching.

Key factors and practical limits of blood extraction from lancet wounds on body sites other than the finger were determined by testing a large number of conditions. During these tests, the pain associated with lancing alternate body sites was rated as less painful than a fingerstick 98% of the time. Vacuum combined with skin stretching was effective in extracting an adequate volume of blood from the forearm for glucose testing, up to an average of 16 microl in 30 s. The amount of blood extracted increases with the application of heat or vacuum before lancing, the level of vacuum, the depth of lancing, the time of collection, and the amount of skin stretching. Vacuum and skin stretching led to significant increases, up to fivefold in the perfusion of blood in the skin as measured by laser Doppler. Our observations suggest that vacuum combined with skin stretching increases blood extraction at alternate sites by increasing the lancet wound opening, increasing the blood available for extraction by vasodilatation, and reducing the venous return of blood through capillaries.