title: Good manufacturing practice-compliant validation and preparation of BM cells for the therapy of acute myocardial infarction.
abstract: BACKGROUND
  Intracoronary application of BM-derived cells for the treatment of acute myocardial infarction (AMI) is currently being studied intensively. Simultaneously, strict legal requirements surround the production of cells for clinical studies. Thus good manufacturing practice (GMP)-compliant collection and preparation of BM for patients with AMI was established by the Cytonet group.
  
  
  METHODS
  As well as fulfillment of standard GMP requirements, including a manufacturing license, validation of the preparation process and the final product was performed. Whole blood (n=6) and BM (n=3) validation samples were processed under GMP conditions by gelafundin or hydroxyethylstarch sedimentation in order to reduce erythrocytes/platelets and volume and to achieve specifications defined in advance. Special attention was paid to the free potassium (<6 mmol/L), some rheologically relevant cellular characteristics (hematocrit <0.45, platelets <450 x 10(6)/mL) and the sterility of the final product.
  
  
  RESULTS
  The data were reviewed and GMP compliance was confirmed by the German authorities (Paul-Ehrlich Institute). Forty-five BM cell preparations for clinical use were carried out following the validated methodology and standards. Additionally three selections of CD34+ BM cells for infusion were performed. All specification limits were met. Discussion In conclusion, preparation of BM cells for intracoronary application is feasible under GMP conditions. As the results of sterility testing may not be available at the time of intracoronary application, the highest possible standards to avoid bacterial and other contaminations have to be applied. The increased expense of the GMP-compliant process can be justified by higher safety for patients and better control of the final product.
authors.affiliation: Cytonet Hannover GmbH, Hannover, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Griesel
authors.forename: H-G
authors.initials: HG
authors.lastname: Heuft
authors.forename: D
authors.initials: D
authors.lastname: Herrmann
authors.forename: A
authors.initials: A
authors.lastname: Franke
authors.forename: D
authors.initials: D
authors.lastname: Ladas
authors.forename: N
authors.initials: N
authors.lastname: Stiehler
authors.forename: A
authors.initials: A
authors.lastname: Stucki
authors.forename: M
authors.initials: M
authors.lastname: Braun
authors.forename: K C
authors.initials: KC
authors.lastname: Wollert
authors.forename: G P
authors.initials: GP
authors.lastname: Meyer
authors.forename: H
authors.initials: H
authors.lastname: Drexler
authors.forename: B
authors.initials: B
authors.lastname: Hertenstein
authors.forename: A
authors.initials: A
authors.lastname: Ganser
authors.forename: W
authors.initials: W
authors.lastname: Rüdinger
authors.forename: L
authors.initials: L
authors.lastname: Arseniev
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology; D002469:Cell Separation / Q000379:methods* / Q000592:standards; D019411:Clinical Laboratory Techniques / Q000592:standards; D005434:Flow Cytometry / Q000379:methods / Q000592:standards; D009203:Myocardial Infarction / Q000628:therapy*; D011786:Quality Control; D015203:Reproducibility of Results
chemical_list: D018952:Antigens, CD34