Privatsphäre-Einstellungen

Herstelllung von Blutstammzellprodukten unter Reinraumbedingungen der Klasse A mit Hintergrundbedingungen der Klasse B

Teil 2*)

Markus Ritter a, Reinier Mutters b, Nimrod Schwella a, Joerg Beyer a, Thomas Wündisch a, Herbert Rüdiger b, Klaus von Jan c und Andreas Neubauer a

Klinik für Hämatologie, Onkologie und Immunologie, Zentrum für Innere Medizin, Philipps-Universität a, Marburg, Institut für medizinische Mikrobiologie und Krankenhaushygiene, Philipps-Universität b, Marburg, und Chiron Behring GmbH & Co .c, Marburg

Preparation of Blood Stem Cell Concentrates under Clean Room Conditions A with Background Conditions B

Part 2

Transplantation of stem cells from the peripheral blood (PBSCs) or bone marrow has become a routine treatment of acute and chronic leukemias. Intensive chemotherapy with or without additional radiotherapy is used as conditioning treatment before the stem cells are transfused intravenously. In the autologous setting patients are being transfused with their own stem cells, which had been harvested and cryopreserved in liquid nitrogen for serveral weeks prior to transplantation. In the allogeneic setting patients usually receive non-cryopreserved stem cells from a suitable sibling or a HLA-matched unrelated donor. In Germany legislation considers harvesting and processing of stem cells as manufacturing of a pharmaceutical product, and reqiures EU-Guidelines of good manufacturing practice (GMP) to be fulfilled. The construction of the clean room laboratory including air conditioning technology and clean room walls was outsourced to a commercial company. In addition to the usual construction standards the CliniMACS cell selection system® was placed under a specially designed "lamina air flow" workbench to achieve clean room conditions A with background conditions B. Moreover a centrifuge, which could have caused clean room contamination in operation, was shielded in a box with an air backflow-system inside.
Monitoring of bacterial contamination was performed "at rest" and "in operation" using different methods such as determination of air particle counts, volumetric air sampling, settle plating, contact plating and 5-finger glove prints. The product qualtiy was verified by analysis of sterility, MNCs, CD34-positve cell count, viability (Trypan blue exclusion method) and determination of colony forming units (CFUs). No bacterial contamination was found in any stem cell product. Settle plates, contact plates and particle counts were distinctly below the required thresholds. However the air sampling exceeded critical thresholds at one point during production procedure. These validation procedures were considered as usefel for our setting. In addition, published alert and action limits were adopted to our laboratory. However, further testings will have to be performed.

Key Words Arzneimittelgesetz (AMG) · Good Manufacturing Practice (GMP) · Periphere Blutstammzellen (PBSC) · Transplantation

*)Teil 1 siehe Pharm. Ind. 64, Nr. 6, S. 601 (2002)