Quality of therapeutic plasma-requirements for marketing authorization.

摘要

Fresh frozen plasma (FFP) contains higher levels of intact coagulation factors and coagulation and fibrinolysis inhibitors than solvent/detergent-treated plasma (SD plasma), and also greater residual cell contamination. SD plasma is a particle-free plasma of uniform quality. SD treatment, however, has the specific result of reducing the activities of some inhibitors. Both plasma types carry a minimal residual risk of transmitting human immunodeficiency virus (HIV)-1/2, hepatitis virus B (HBV), and hepatitis virus C (HCV), but SDP is, in addition, also safe with respect to other lipid-enveloped viruses and perhaps with respect to hepatitis virus A (HAV), also due to its antibody (Ab) content.Future revisions of therapeutic plasma safety and quality standards should consider the following points:For FFP:reduce residual cell count in all FFP units to values below 5x10(6) leukocytes/l;screen donors for Parvovirus B19 genome and antibodies in order to establish a sufficiently large collection of genome-negative and antibody-positive donors whose FFP can be used for selected patients;For SDP:introduce pool testing for Parvovirus B19 genome; fix an upper limit for genome and a lower limit for antibody content;in addition to the standard quality control methods for therapeutic plasma, focus on assays to test for functionally intact proteinase inhibitors such as alpha(2)antiplasmin (alpha(2)AP) and alpha(1)proteinase inhibitor (alpha(1)PI) that are important for plasma indications. Commercially available kits may not be sufficient to show changes in inhibition kinetics.For both types:introduce an activation marker such as thrombin-antithrombin complex (TAT) as a random test to monitor activation processes during withdrawal, separation, manufacturing, and storage;abolish inappropriate parameters like Antithrombin III (AT III) and coagulation factor XI that are not relevant for changes in plasma quality;finally, support every effort towards establishing an efficient documentation and reporting system on efficacy and side effects of plasma transfusions. Effective reporting alone might help to reveal deficiencies of specific plasma quality and to overcome them through modifications to manufacturing processes and testing, or by defining its indications more precisely.