[Quality assurance in transfusion medicine from an international viewpoint]. / Qualitätssicherung in der Transfusionsmedizin aus internationaler Sicht.

International, European and National laws and guidelines require to establish a Quality Assurance System for manufacturers and distributors of drugs. This includes all departments involved in manufacturing, quality control and distribution. On the basis of validated written Standard Operation Procedures and documentation of all single processes a high standard for the safety of drugs is achieved. In addition, retracing from the finished product lot and the customer back to raw materials and suppliers is possible.

Validation of virus inactivation and removal for the manufacturing procedure of two immunoglobulins and a 5% serum protein solution treated with beta-propiolactone.

Intravenous immunoglobulins and serum protein solutions are manufactured from human plasma pools of healthy, screened donors. A step-by-step validation of virus removal and/or inactivation was performed for the manufacturing process, which includes cold ethanol fractionation, beta-propiolactone (beta-PL) treatment, UV irradiation, thermal inactivation and other chemical and physical purification steps. The total viral clearance factors achieved for the entire manufacturing process were by several magnitudes greater than the potential virus load of current plasma pools. Human immunodeficiency virus 1 (HIV-1) infectivity was reduced by > 13.4 log for 7S immunoglobulin, > 15.3 log for IGM enriched immunoglobulin and > 16 log for a 5% serum protein solution. In addition, high clearance rate for a broad spectrum of model viruses was demonstrated for all three blood derivatives being > 23.2 to > 27.8 log for pseudo rabies virus (PSR), > 12.3 to > 22.6 log for vesicular stomatitis virus (VSV) and 6.9-10.6 log for simian virus 40 (SV40). For the beta-propiolactone inactivation step Hepatitis C model viruses, e.g. equine arteritis virus (EAV) and bovine viral diarrhoea virus (BVDV) were also investigated.

[49 day storage of erythrocyte concentrates in blood bags with the PAGGS-mannitol solution]. / 49 Tage Lagerung von Erythrozytenkonzentraten in Blutbeuteln mit der Konservierungslösung PAGGS-Mannitol.

The red cell preservation solution PAGGS-Mannitol differs from the well documented PAGGS-Sorbitol only by the exchange from Sorbitol in Mannitol. In a clinical investigation with volunteers, up to 21 of the pure PAGGS-Mannitol solution were infused within 4 h. Blood and urine parameters were determined. The solution was well tolerated, no unexpected change of blood and urine parameters was found. The 24 h red cell in vivo survival rate of PAGGS-Mannitol was found to be 74.5 +/- 4.4%, after 49 days storage, a value which was described for PAGGS-Sorbitol before. In vitro data on storage of red cell concentrates with and without buffy coat were determined for hemolysis, 2,3-DPG and ATP using a blood bag system with DEHP and TOTM plastisized PVC. If 1% hemolysis is regarded as acceptable, red cell concentrates can be stored in PAGGS-Mannitol with a TOTM plastisized blood bag system up to 42 days. Under these conditions the amount of plastisizer in the red cell concentrate was found to be only 1% of the amount determined in a standard DEHP plastisized PVC blood bag system.

[Determination of purine derivatives in blood and plasma fractions]. / Bestimmung von Purinderivaten im Blut und in Plasmafraktionen

A method is described for the separation of adenine and guanosine from whole blood and plasma fractions, containing purinderivatives as anticoagulant-additives. The highest concentration determined per gram human albumin or gamma-globulin was 0.5 mg. Due to interactions with blood cells guanosine could only be detected in plasma which was stored for more than one week as whole blood. The amount of adenine and guanosine to be expected in therapeutical products is uncritical according to published pharmacological investigations.