NetCord - FACT International Standards for Cord Blood Collection, Banking, and Release for Administration

The requirements specified below are based on the 7th edition 2019 of the NetCord-FACT international standards for cord blood collection, banking, and release for administration (Reference 5) and outlined in

  • Part B7: Equipment
  • Part B8: Supplies and Reagents
  • Part B11: Documents and Records
  • Part D3: Cord Blood Processing
  • Part D9: Cord Blood Unit testing
  • Appendix IV: Testing Requirements

NetCord-FACT Identifier/Requirement

AQUIOS STEM System

  • B7.1 The cord blood bank (CBB) shall establish policies and Standard Operating Procedures for the management of critical equipment including identification, qualification, calibration, and maintenance.5
  • Each AQUIOS CL unit can be identified through a unique serial number.
  • AQUIOS STEM CD34 Control Cells are liquid preparations of stabilized human leukocytes for the verification of the parameters CD34 and CD45 as part of the AQUIOS STEM System.
  • AQUIOS CL instrument settings are monitored specifically for the AQUIOS STEM System by running Flow-Check Fluorospheres.
  • Maintenance procedures are described in the AQUIOS CL Instructions For Use, PN B21896.
  • B7.1.1 All critical equipment shall be defined and qualified for the intended use.5
  • AQUIOS STEM System is validated for the detection of the parameters in the specimen types shown in Table 1.1, System Parameters in Chapter 1 of the AQUIOS STEM System Guide.
  • B7.1.2 Equipment should be used in accordance with the manufacturer’s instructions.5
  • B7.2 Equipment shall be used in a manner that prevents CB unit mix-ups, contamination, and cross-contamination, and that does not compromise unit function and integrity.5
  • If specimen tubes are barcoded, and the LIS connection is enabled, the system automatically retrieves the test request from the LIS. For specimen tubes that are not barcoded, specimen ID and demographic data can be entered manually.
  • The system uses an internal barcode scanner for positive sample tracking of autoloader samples. The sample ID is matched to the request and the patient information is readily accessible throughout the sample process.
  • B7.3 Equipment records shall include the manufacturer’s name, serial number or other unique identifier, manufacturer’s instructions, equipment location, and use of each piece of equipment, including the identification of each CB unit for which the equipment was used.5
  • Each AQUIOS CL unit can be identified through a unique serial number.
  • The system automatically records and stores this information together with the sample ID for both electronic data files and manual printouts.
  • B7.3.1 There shall be a mechanism to identify which piece of equipment was used for each CB unit.5
  • Each AQUIOS CL unit can be identified through a unique serial number.
  • The system automatically records and stores this information together with the sample ID for both electronic data files and manual printouts.
  • B7.4.1 Equipment shall be inspected, tested, and calibrated on a regularly scheduled basis as recommended by the manufacturer, after a critical repair or move, and, at a minimum, annually.5
  • To ensure ongoing compliance and instrument performance, Beckman Coulter Life Sciences offers programs for instrument service, preventive maintenance, and confirmation of system operation.
  • Setup and maintenance procedures are described in Chapter 9 of the AQUIOS CL Instructions For Use, PN B21896.
  • B7.4.2 All equipment with a critical measuring function shall be calibrated against a traceable standard, if available. Where no traceable standard is available, the basis and acceptance criteria for calibration shall be described and documented.5
  • AQUIOS STEM CD34 Control Cells are liquid preparations of stabilized human leukocytes for the verification of the parameters CD34 and CD45 as part of the AQUIOS STEM System. Resulting QC data is monitored for each lot in the QC database.
  • AQUIOS CL instrument voltages are monitored specifically for the AQUIOS STEM System by running Flow-Check Fluorospheres.
  • The AQUIOS STEM Software QC module provides access to eIQAP, Beckman Coulter’s electronic Interlaboratory Quality Assurance Program, which allows users to obtain peer group comparison reports for their laboratory’s quality control data.
  • B7.4.3 When equipment is found to be out of calibration or specification, there shall be a defined process for action required for CB units manufactured since the last calibration.5
  • AQUIOS CL Troubleshooting procedures are described in Chapter 9 of the AQUIOS CL Instructions For Use, PN B21896.
  • B7.4.4 Records of the dates and copies of calibration results shall be maintained.5
  • AQUIOS STEM CD34 Control Cells are liquid preparations of stabilized human leukocytes for the verification of the parameters CD34 and CD45 as part of the AQUIOS STEM System. Resulting QC data is monitored for each lot in the QC database.
  • B7.5.1 Equipment shall be maintained in a clean and orderly manner and located so as to facilitate cleaning, sanitation, calibration, and maintenance according to established schedules.5
  • AQUIOS CL Cleaning procedures are described in Chapter 10 of the AQUIOS CL Instructions For Use, PN B21896.
  • B7.5.2 Records of the maintenance schedule; maintenance performed; and damage, malfunction, modification, or repair to equipment shall be maintained.5
  • To ensure ongoing compliance and instrument performance, Beckman Coulter Life Sciences offers programs for instrument service, preventive maintenance, and confirmation of system operation.
  • B7.5.3 There shall be a Standard Operating Procedure that addresses the actions to take in the event of equipment malfunction or failure.5
  • AQUIOS CL Troubleshooting procedures are described in Chapter 9 of the AQUIOS CL Instructions For Use, PN B21896.
  • B7.6.1 Equipment shall be cleaned and sanitized according to established schedules.5
  • AQUIOS CL Cleaning procedures are described in Chapter 10 of the AQUIOS CL Instructions For Use, PN B21896.
  • B8.1 Vendors for all critical reagents and supplies shall be qualified.5
  • The AQUIOS STEM System, comprised of AQUIOS STEM Software for the AQUIOS CL Flow Cytometry System, AQUIOS STEM Kit Reagents, AQUIOS STEM CD34 Control Cells and Flow-Check Fluorospheres, is an in vitro diagnostic medical device intended to be used by laboratory professionals for the detection of the parameters in the specimen types shown in Table 1.1, System Parameters in Chapter 1 of the AQUIOS STEM System Guide on the automated AQUIOS CL Flow Cytometry System.
  • B8.2 Critical reagents and supplies shall be defined and qualified to function as expected.5
  • AQUIOS STEM System is validated for the detection of the parameters in the specimen types shown in Table 1.1, System Parameters in Chapter 1 of the AQUIOS STEM System Guide.
  • AQUIOS STEM CD34 Control Cells are liquid preparations of stabilized human leukocytes for the verification of the parameters CD34 and CD45 as part of the AQUIOS STEM System. Resulting QC data is monitored for each lot in the QC database.
  • B8.4 Supplies and reagents that come into contact with the CB unit during collection, processing, or storage shall be sterile and of the appropriate grade for the intended use.5
  • The AQUIOS STEM System, comprised of AQUIOS STEM Software for the AQUIOS CL Flow Cytometry System, AQUIOS STEM-Kit Reagents, AQUIOS STEM CD34 Control Cells and Flow-Check Fluorospheres, is an in vitro diagnostic medical device intended to be used by laboratory professionals for the detection of the parameters in the specimen types shown in Table 1.1, System Parameters in Chapter 1 of the AQUIOS STEM System Guide on the automated AQUIOS CL Flow Cytometry System.
  • As the reagents are for IVD use, they are not sterile.
  • B8.4.1 If suitable clinical or pharmaceutical grade reagents are not used, reagents shall undergo lot-to-lot functional verification and shall include acceptance criteria to confirm that new lots perform as expected compared to the previous lots.5
  • The AQUIOS STEM System, comprised of AQUIOS STEM Software for the AQUIOS CL Flow Cytometry System, AQUIOS STEM-Kit Reagents, AQUIOS STEM CD34 Control Cells and Flow-Check Fluorospheres, is an in vitro diagnostic medical device intended to be used by laboratory professionals for the detection of the parameters in the specimen types shown in Table 1.1, System Parameters in Chapter 1 of the AQUIOS STEM System Guide on the automated AQUIOS CL Flow Cytometry System.
  • B8.5 Supplies and reagents used for CB collection, processing, or cryopreservation, whenever possible, shall be approved for human use.5
  • AQUIOS STEM System is validated for the detection of the parameters in the specimen types shown in Table 1.1, System Parameters in Chapter 1 of the AQUIOS STEM System Guide.
  • B8.6 Certificates of analysis shall be obtained and maintained indefinitely on file for all critical reagents.5
  • B8.7 Supplies and reagents should be used in a manner consistent with instructions provided by the manufacturer.5

Please refer to the following documents:

  • AQUIOS CL Instructions For Use, PN B21896
  • AQUIOS STEM System Guide, PN B75978
  • B8.9 The lot number, expiration date, and manufacturer of supplies and reagents used for collection, processing, testing, cryopreservation, or storage of each CB unit shall be documented and linked to each CB unit.5
  • AQUIOS STEM reagents use a unique barcode identity for tracking reagent type, lot number, container number, and expiration dates.
  • The system automatically records and stores this information.
  • B8.10 There shall be a process to prevent the use of expired reagents and supplies.5
  • AQUIOS STEM reagents use a unique barcode identity for tracking reagent type, lot number, container number, expiration dates, and remaining reagent levels.
  • The system warns the user in case an expired reagent is used for analysis.
  • D3.2.3 Information regarding processing steps that have been completed on a CB unit shall accompany the CB unit or be available electronically during all stages of processing.5
  • If specimen tubes are barcoded, and the LIS connection is enabled, the system automatically retrieves the test request from the LIS. For specimen tubes that are not barcoded, specimen ID and demographic data can be entered manually.
  • The system uses an internal barcode scanner for positive sample tracking of autoloader samples. The sample ID is matched to the request and the patient information is readily accessible throughout the sample process.
  • D3.2.4 Processing and cryopreservation of CB units shall be performed according to Standard Operating Procedures validated to result in acceptable cell viability, recovery, and potency.5
  • AQUIOS STEM Kit contains 7-AAD to analyze cell viability for each run.
  • AQUIOS STEM Software reports both the number of viable CD34+ cells AND the total number of CD34+ cells.
  • D9.2.1 The use of established and validated assays, equipment, and test procedures for the evaluation of the CB unit.5
  • AQUIOS STEM System is validated for the detection of the parameters in the specimen types shown in Table 1.1, System Parameters in Chapter 1 of the AQUIOS STEM System Guide.
  • D9.2.2 Adequate provisions for monitoring the reliability, accuracy, precision, and performance of test procedures and instruments.5
  • Criteria used for establishing AQUIOS STEM performance data are specified in Chapter 6 of the AQUIOS STEM System Guide, PN B75978.
  • AQUIOS STEM CD34 Control Cells are liquid preparations of stabilized human leukocytes for the verification of the parameters CD34 and CD45 as part of the AQUIOS STEM System. Resulting QC data is monitored for each lot in the QC database.
  • AQUIOS CL instrument voltages are monitored specifically for the AQUIOS STEM System by running Flow-Check Fluorospheres.
  • D9.2.3 Adequate identification and handling of all samples so that they are accurately related to the specific CB unit being tested, to its infant donor, to the maternal donor, and to the specific recipient, as applicable.5
  • If specimen tubes are barcoded, and the LIS connection is enabled, the system automatically retrieves the test request from the LIS. For specimen tubes that are not barcoded, specimen ID and demographic data can be entered manually.
  • The system uses an internal barcode scanner for positive sample tracking of autoloader samples. The sample ID is matched to the request and the patient information is readily accessible throughout the sample process. For specimen tubes that are not barcoded, specimen ID and demographic data can be entered manually.
  • D9.2.4 Verification of new reagent lots to provide comparable results between lots or give results in agreement with suitable reference ranges before or with placement into service.5
  • AQUIOS STEM CD34 Control Cells are liquid preparations of stabilized human leukocytes for the verification of the parameters CD34 and CD45 as part of the AQUIOS STEM System. Resulting QC data is monitored for each lot in the QC database.
  • AQUIOS CL instrument voltages are monitored specifically for the AQUIOS STEM System by running Flow-Check Fluorospheres.
  • D9.2.5 Where available, use of reference or quality control material demonstrated to give results within the defined range established for that material.5
  • AQUIOS STEM CD34 Control Cells are liquid preparations of stabilized human leukocytes for the verification of the parameters CD34 and CD45 as part of the AQUIOS STEM System. Resulting QC data is monitored for each lot in the QC database.
  • AQUIOS CL instrument voltages are monitored specifically for the AQUIOS STEM System by running Flow-Check Fluorospheres.
  • D9.2.6 Functional checks performed for testing instruments, as appropriate, prior to testing of CB units.5
  • AQUIOS STEM CD34 Control Cells are liquid preparations of stabilized human leukocytes for the verification of the parameters CD34 and CD45 as part of the AQUIOS STEM System. Resulting QC data is monitored for each lot in the QC database.
  • AQUIOS CL instrument voltages are monitored specifically for the AQUIOS STEM System by running Flow-Check Fluorospheres.
  • D9.2.7 Documentation of ongoing proficiency testing as designated by the CB Processing Facility Director.5
  • The AQUIOS STEM Software QC module provides access to eIQAP, Beckman Coulter’s electronic Interlaboratory Quality Assurance Program, that allows users to obtain peer group comparison reports for their laboratory’s quality control data.
  • D9.3 CB units shall be tested as outlined in the Testing Requirements table in Appendix IV.5
  • CB samples: Pre-processing (end of collection)
  • CBC with differential5
  • AQUIOS STEM Software reports the total number of CD45+ cells in the sample. For a complete blood count (CBC) with differential, we recommend the use of a suitable hematology analyzer.
  • CB samples: Post-processing prior to cryopreservation
  • Total nucleated cell count5
  • AQUIOS STEM Software reports the total number of CD45+ cells in the sample. For a total nucleated cell count, we recommend the use of a suitable hematology analyzer.
  • Nucleated red blood cell count5
  • AQUIOS STEM Software reports the total number of CD45+ cells in the sample. For a nucleated red blood cell count, we recommend the use of a suitable hematology analyzer.
  • Total CD345
  • AQUIOS STEM Software reports both the number of viable CD34+ cells AND the total number of CD34+ cells.
  • AQUIOS STEM Software allows users to enter the dilution factor as well as the volume of sample, which are then used to automatically calculate the corrected value.
  • Total viable CD345
  • AQUIOS STEM Software reports both the number of viable CD34+ cells AND the total number of CD34+ cells.
  • AQUIOS STEM Software allows users to enter the dilution factor as well as the volume of sample, which are then used to automatically calculate the corrected value.
  • % Viability of total nucleated cell count5
  • AQUIOS STEM Software reports the number of both viable and total CD45+ cells (WBC) for each run, as well as CD45+ cell viability.
  • AQUIOS STEM Kit contains 7-AAD to analyze cell viability.
  • CFU or other validated potency assay (should be performed)5

N/A for flow cytometry

  • Microbial culture5

N/A for flow cytometry

  • CB samples: Any time prior to cryopreservation
  • ABO/Rh blood group5

N/A for flow cytometry

  • CB samples: On an appropriate sample type at any time prior to listing
  • HLA Tissue Typing5

N/A for flow cytometry

  • Tests for the identification of infectious diseases5

N/A for flow cytometry

  • CB samples: Thawed contiguous segment or representative sample prior to release to the Clinical Program
  • Total nucleated cell count (should be performed)5
  • AQUIOS STEM Software reports the total number of CD45+ cells in the sample. For a total nucleated cell count, we recommend the use of a suitable hematology analyzer.
  • Total viable CD34 (should be performed)5
  • AQUIOS STEM Software reports both the number of viable CD34+ cells AND the total number of CD34+ cells.
  • AQUIOS STEM Software allows entering the dilution factor as well as the volume of sample, which are then used to automatically calculate the corrected total cell number.
  • % Viability of total nucleated cell count5
  • AQUIOS STEM Software reports the number of both viable and total CD45+ cells (WBC) for each run, as well as CD45+ cell viability.
  • AQUIOS STEM Kit contains 7-AAD to analyze cell viability.
  • % Viability of CD345
  • AQUIOS STEM Kit contains 7-AAD to analyze cell viability.
  • AQUIOS STEM Software reports both the number of viable CD34+ cells AND the total number of CD34+ cells, as well as CD34+ cell viability.
  • CFU or other validated potency assay5

N/A for flow cytometry

  • HLA Tissue Typing5

N/A for flow cytometry

  • CB samples: On an appropriate sample type at any time prior to release
  • HLA Tissue Typing5

N/A for flow cytometry

  • Hemoglobinopathy5

N/A for flow cytometry

  • Maternal samples obtained within seven (7) days before or after CB collection
  • Tests for the identification of infectious diseases5

N/A for flow cytometry

International guidelines and standards for CD34+ hematopoietic stem and progenitor cells analysis

References

  1. Sutherland DR, Anderson L, Keeney M, Nayar R, Chin-Yee I: The ISHAGE guidelines for CD34+ cell determination by flow cytometry. International Society of Hematotherapy and Graft Engineering. J Hematother. 1996 Jun;5(3):213-26.
  2. Keeney M, Chin-Yee I, Weir K, Popma J, Nayar R, Sutherland DR: Single platform flow cytometric absolute CD34+ cell counts based on the ISHAGE guidelines. International Society of Hematotherapy and Graft Engineering. Cytometry. 1998 Apr 15;34(2):61-70.
  3. EDQM Council of Europe: European Pharmacopoeia (Ph. Eur.). 10th Edition 2019-2022. Website: https://pheur.edqm.eu/home
  4. Foundation for the Accreditation of Cellular Therapy (FACT), Joint Accreditation Committee – ISCT and EBMT (JACIE): International standards for hematopoietic cellular therapy product collection, processing, and administration. 8th Edition, Version 8.1, 2021. Website: http://www.factwebsite.org/
  5. Foundation for the Accreditation of Cellular Therapy (FACT): NetCord-FACT international standards for cord blood collection, banking, and release for administration. 7th Edition, 2019. Website: http://www.factwebsite.org/
  6. Whitby A, Whitby L, Fletcher M, Reilly JT, Sutherland DR, Keeney M, Barnett D: ISHAGE protocol: are we doing it correctly? Cytometry B Clin Cytom. 2012 Jan;82B:9-17.

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