FACT - JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration

The requirements specified below are based on the 8th Edition (8.1) 2021 of the International standards for hematopoietic cellular therapy product collection, processing, and administration (Reference 4) and outlined in

  • Part D6: Processing Facility Standards: Equipment, Supplies and Reagents
  • Part D8: Processing Facility Standards: Process controls

FACT-JACIE Identifier/Requirement

AQUIOS STEM System

D6.3 Supplies and reagents used in processing, testing, cryopreservation, and storage shall be controlled by a materials management system that includes requirements for the following at a minimum:

  • D6.3.2 Records of receipt that shall include the supply or reagent type, quantity, manufacturer, lot number, date of receipt, acceptability, and expiration date.4
  • AQUIOS STEM reagents use a unique barcode identity for tracking reagent type, lot number, container number, expiration dates, and remaining reagent levels. The reagent consumption is monitored by the system as the samples are processed.
  • D6.3.4.1 Reagents shall undergo initial qualification for the intended use.4
  • 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.
  • D6.3.4.3 Lot-to-lot functional verification shall include acceptance criteria to confirm that new lots perform as expected compared to the previous lots.4
  • 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.
  • D6.3.4.3 Lot-to-lot functional verification shall include acceptance criteria to confirm that new lots perform as expected compared to the previous lots.4
  • 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.
  • D6.3.5 Cleaning and sterilizing of non-disposable supplies or instruments using a procedure verified to remove infectious agents and other contaminants.4
  • Please refer to Chapter 10 of the AQUIOS CL Instructions For Use, PN B21896, for cleaning and sterilizing procedures.
  • D6.3.7 Process to prevent the use of expired reagents and supplies.4
  • 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.
  • D6.4 There shall be a system to uniquely identify and track all critical equipment used in the processing of cellular therapy products. The system shall identify each cellular therapy product for which the equipment was used.4
  • 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.
  • AQUIOS STEM Software allows users to enter additional data, such as Patient ID, Gender, Date of Birth, Collect Date, Analysis Date, Physician Name, Physician Code, Location, Harvest Volume, Body Weight, and specimen dilution factor.
  • D6.7 The equipment shall be standardized and calibrated on a regularly scheduled basis and after a critical repair or move as described in Standard Operating Procedures and in accordance with the manufacturer’s recommendations.4
  • The AQUIOS CL Flow Cytometer is a quantitative automated analyzer that performs the STEM diagnostic applications in a “no-wash” sample preparation process. Since this system is intended to be an automated analyzer with hands-off processing of samples from specimen introduction to results reports, it is referred to as a Load & Go flow cytometer. The AQUIOS System Software and AQUIOS STEM Tests and Quality Control Reagents do not require user verification of standardization of light scatter, and fluorescence intensities.
  • 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 settings are monitored specifically for the AQUIOS STEM System by running Flow-Check Fluorospheres.
  • D6.7.1 All equipment with a critical measuring function shall be calibrated against a traceable standard, if available. Where no traceable standard is available, the basis for calibration shall be described and documented.4
  • 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.
  • D6.8 There shall be a Standard Operating Procedure that addresses the actions to take in the event of equipment malfunction or failure.4
  • Please refer to Chapter 9, Troubleshooting, of the AQUIOS CL Instructions For Use, PN B21896.
  • D6.9 Equipment shall conform to Applicable Law.4
  • 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.
  • D6.10 Lot numbers, expiration dates, manufacturers of critical reagents and supplies, and key equipment used in each procedure shall be documented.4
  • AQUIOS STEM reagents use a unique barcode identity for tracking reagent type, lot number, container number, expiration dates, and remaining reagent levels.

D6.11 The Processing Facility shall use an inventory control system to document the availability and identity of critical reagents and supplies. This shall include at a minimum:

  • D6.11.1 A system to uniquely identify and track all critical reagents and supplies used to manufacture cellular therapy products.4
  • AQUIOS STEM reagents use a unique barcode identity for tracking reagent type, lot number, container number, and expiration dates.
  • D6.11.2 A system to identify each cellular therapy product for which each critical reagent or supply was used.4
  • The AQUIOS Smart Scheduler tracks requests as they proceed from sample preparation to analysis. All AQUIOS reagents are continuously monitored by the system to track reagent consumption and location changes. The acquired data is stored and provides immediate data access for laboratories.
  • AQUIOS STEM reagents use a unique barcode identity for tracking reagent type, lot number, container number, expiration dates, and remaining reagent levels. The reagent consumption is monitored by the system as the samples are processed.

D8.1 There shall be a process for controlling and monitoring the manufacturing of cellular therapy products so that products meet predetermined release specifications.

  • D8.1.2 There shall be a documented system for the identification and handling of test samples so that they are accurately related to the corresponding cellular therapy product, donor, or recipient.4
  • 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.
  • AQUIOS STEM Software allows users to enter additional data, such as Patient ID, Gender, Date of Birth, Collect Date, Analysis Date, Physician Name, Physician Code, Location, Harvest Volume, Body Weight, and specimen dilution factor.
  • D8.1.3 There shall be the establishment of appropriate and validated assays and test procedures for the evaluation of cellular therapy products.4
  • 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.
  • D8.1.3.1 For all cellular therapy products, a total nucleated cell count and viability measurement shall be performed.4
  • AQUIOS STEM Kit contains 7-AAD to analyze cell viability for each run.
  • AQUIOS STEM Software reports the following parameters:
    • Number of viable CD45+ cells
    • Number of total CD45+ cells (WBC)
  • D8.1.3.2 For HPC products intended for restoration of hematopoiesis, an assay measuring viable CD34 shall be performed.4
  • 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.
  • D8.1.3.3 For cellular therapy products undergoing manipulation that alters the final cell population, a relevant and validated assay, where available, shall be employed for evaluation of the viable target cell population before and after the processing procedures.4
  • 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.
  • D8.1.4.1 There shall be a process for monitoring the reliability, accuracy, precision, and performance of laboratory test procedures and instruments.4
  • Criteria used for establishing AQUIOS STEM performance data are specified in 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.
  • D8.1.4.2 New reagent lots shall be verified to provide comparable results to current lots or to give results in agreement with suitable reference material before or concurrently with being placed into service.4
  • 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 STEM reagents use a unique barcode identity for tracking reagent type, lot number, container number, expiration dates, and remaining reagent levels. The reagent consumption is monitored by the system as the samples are processed.
  • D8.1.4.3 Where available, controls shall be used each day of testing and shown to give results within the defined range established for that material.4
  • 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.
  • D8.1.4.4 Function checks shall be performed for testing instruments prior to testing donor, recipient, or cellular therapy product samples.4
  • 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.
  • D8.1.4.5 For tests performed within the Processing Facility, there shall be documentation of ongoing proficiency testing as designated by the Processing Facility Director.4
  • 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.
  • D8.9 Records shall be made concurrently with each step of the processing, testing, cryopreservation, storage, and administration or disposal/disposition/ distribution of each cellular therapy product in such a way that all steps may be accurately traced.4
  • 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.
  • AQUIOS STEM Software allows users to enter additional data, such as Patient ID, Gender, Date of Birth, Collect Date, Analysis Date, Physician Name, Physician Code, Location, Harvest Volume, Body Weight, and specimen dilution factor.
  • D8.9.1 Records shall identify the person immediately responsible for each significant step, including dates and times, where appropriate.4
  • AQUIOS STEM Software records the User signed on to the system when the test is performed.
  • In addition, the name and ID of the physician performing the test can be entered manually. The printed report contains a signature field.
  • AQUIOS STEM reports provide time stamps for sample acquisition and data analysis.
  • D8.9.2 Records shall show the test results and the interpretation of each result, where appropriate.4
  • AQUIOS STEM Software provides the data plots required by the ISHAGE sequential gating strategy, as well as relevant statistics parameters.
  • Test results are stored in the AQUIOS CL database. Reports can be printed or saved (PDF) from the Review or the Result screens.

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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