No abstract

Fibrin sealant is a complex plasma-derived product which is increasingly used as a biodegradable tissue adhesive or sealant to stop or control bleeding or provide air and fluid tightness in many surgical situations. This review describes the historical development of current fibrin sealant preparations and the scientific rationale behind the alleged physiological benefits of its major plasma-derived components. A comparison in the extraction methods and viral reduction treatments applied to current commercial products and autologous preparations, and their respective advantages and limits, are discussed. Application devices used for surgical applications are described. A survey of the major clinical applications in various surgical areas is presented. Current issues in terms of viral safety, definition of optimal fibrin sealant composition, and regulatory concerns, especially to demonstrate clinical efficacy, are also included.

Intravenous immunoglobulin G (IVIG) is now the leading product obtained by fractionation of human plasma. It is the standard replacement therapy in primary and acquired humoral deficiency, and is also used for immunomodulatory therapy in various autoimmune disorders and transplantation. Over the last 30 years, the production processes of IVIG have evolved dramatically, gradually resulting in the development of intact IgG preparations safe to administer intravenously, with normal half-life and effector functions, prepared at increased yield, and exhibiting higher pathogen safety. This article reviews the developments that have led to modern IVIG preparations, the current methods used for plasma collection and fractionation, the safety measures implemented to minimize the risks of pathogen transmission and the major quality control tests that are available for product development and as part of mandatory batch release procedures.

Fibrin sealant is a complex plasma-derived product which is increasingly used as a biodegradable tissue adhesive or sealant to stop or control bleeding or provide air and fluid tightness in many surgical situations. This review describes the historical development of current fibrin sealant preparations and the scientific rationale behind the alleged physiological benefits of its major plasma-derived components. A comparison in the extraction methods and viral reduction treatments applied to current commercial products and autologous preparations, and their respective advantages and limits, are discussed. Application devices used for surgical applications are described. A survey of the major clinical applications in various surgical areas is presented. Current issues in terms of viral safety, definition of optimal fibrin sealant composition, and regulatory concerns, especially to demonstrate clinical efficacy, are also included.

Solvent-detergent (S/D) viral inactivation was recently adapted to the treatment of single plasma donations and cryoprecipitate minipools. We present here a new process and a new bag system where the S/D reagents are removed by filtration and the final products subjected to bacterial (0.2 microm) filtration. Recovered and apheresis plasma for transfusion (FFP) and cryoprecipitate minipools (400 +/- 20 mL) were subjected to double-stage S/D viral inactivation, followed by one oil extraction and a filtration on a S/D and phthalate [di(2-ethylhexyl) phthalate (DEHP)] adsorption device and a 0.2 microm filter. The initial and the final products were compared for visual appearance, blood cell count and cell markers, proteins functional activity, von Willebrand factor (VWF) multimers and protein profile by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Tri (n-butyl) phosphate (TnBP) was quantified by gas chromatography and Triton X-45 and DEHP by high-performance-liquid chromatography (HPLC). General safety tests were by 6.5 mL/kg intravenous injection in rats. The treated plasmas and cryoprecipitates were very clear and the protein content and functionality, VWF multimers and SDS-PAGE profiles were well preserved. TnBP and Triton X-45 were < 1 and <25 ppm, respectively, and DEHP (about 5 ppm) was less than it was in the starting materials. Blood cell counts and CD45, CD61 and glycophorin A markers were negative. There was no enhanced toxicity in rats. Thus, plasma and cryoprecipitate can be S/D-treated in this new CE-marked disposable integral processing system under conditions preserving protein function and integrity, removing blood cells, S/D agents and DEHP, and ensuring bacterial sterility. This process may offer one additional option to blood establishments for the production of virally inactivated plasma components.