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Haematopoietic Progenitor Cell Processing Standards and Inspection of Laboratory Facilities

Haematopoietic Progenitor Cell Processing Standards and Inspection of Laboratory Facilities. JACIE inspector training. JACIE International Standards – Third Edition Part D: Cellular therapy product processing standards D1 General D2 Processing facility D3 Personel D4 Quality Management

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Haematopoietic Progenitor Cell Processing Standards and Inspection of Laboratory Facilities

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  1. Haematopoietic Progenitor Cell Processing Standards and Inspection of Laboratory Facilities

  2. JACIE inspector training • JACIE International Standards – Third Edition • Part D: Cellular therapy product processing standards • D1 General • D2 Processing facility • D3 Personel • D4 Quality Management • D5 Policies and Procedures • D6 Process Controls • D7 Labels • D8 Cellular Product Distribution • D9 Storage • D10 Receipt and Transportation • D11 Disposal • D12 Records

  3. JACIE inspector training D General D1.1Standards apply to all processing, storage and distribution activities performed in the laboratory for cellular therapy products D1.2 In agreement with all applicable national laws and regulations D1.3 Facility and staff shall have been in place and performing cell processing for at least one year prior to being eligible for accreditation

  4. JACIE inspector training D2 Processing facility: the inspection • Overall impression of organisation • Observe an ongoing procedure • Staff/equipement in relation to workload • Questions to staff – most junior? • Safety manual

  5. JACIE inspector training • D2 Processing facility: the standards • D2.1 General • Adequate space and defined areas • Maintained in a clean, sanitary and orderly manner • Adequate equipement for intended procedures – MAINTENANCE RECORDS / CONTRACTS • Admittance restricted to authorised personnel • D2.2 Safety requirements • Safety manual (biological and chemical hazards, exposure to communicable diseases) • Gloves and protecting clothing (only inside the work area)

  6. JACIE inspector training • D3 Personnel: the standards • Processing facility director (MD or PhD) (D3.1) • Processing Facility Medical Director (responsible for medical aspects) (D3.2) • Regular participation in educational activities related to the field of cellular • processing and/or administration • Adequate trained staff for the volume and complexity of all operations (D3.3) • Quality management supervisor

  7. JACIE inspector training D3 Personnel: the inspection • Evaluation of CVs* • Organisational chart* • Role Medical Laboratory Director? • Job descriptions • Education and training and competency • (in individual files) • Adequate staff in relation to workload • * “at home”

  8. JACIE inspector training • D4 Quality Management : the standards(1) • Written Quality Management Plan(D4.1) • Processing Facilty director responsible, delegate to a designated person(D4.2) • Organizational chart of key personnel and description of functions (D4.3) • Written agreement with a third party for external activities • Methods for processdevelopment, approval, validation, implementation, review, revision • for all critical processes, policies and procedures (D4.5) • Personnel requirements (job description, training, competency, training, re-training) • (D4.6) • Minimal trainer qualifications and uniform plan for staff training(D4.7) • Documentation and review of product efficacy (time to engraftment) (D4.8) • Quality audits (plan, individual with sufficient expertise, review of reports, improvements) • (D4.9)

  9. JACIE inspector training D4 Quality Management: the inspection • Quality management manual (overall description of system) • Interview Laboratory director and QM supervisor • (specific responsabilities, collaboration) • Central QM coordinator in the institute? • Example of recent audit report • Follow-up and actions taken after audit • Records of engraftment • Outcome analysis: tables, files, meetings?

  10. JACIE inspector training • D4 Quality Management: the standards (2) • System for detection, evaluating, documenting and reporting errors, accidents, ... • (written description to the recipients physician) (D4.10) • Mechanism for document control and regular review of records (D4.11) • Process for product tracking (validation and verification of critical reagents, • equipments and procedures) (D4.12) • Process for qualification of critical supplies, reagents, equipment, procedures and • facilities (cleaning and sanitation, storage of supplies and reagents, calibration and • maintenance of equipment) (D4.13) • Process for inventory control(D4.14) • Process for controlling and monitoring the manufacturing of cellular therapy products • (tests for measuring safety, viability and integrity of the products; proficiency-testing) • (D4.15)

  11. JACIE inspector training D4 Quality Management: the inspection • Documentation and actions undertaken after • unexpected event (policy) • Validation report of particular procedure or device • Logbooks • Storage of reagents and supplies

  12. JACIE inspector training • D5 Policies and procedures: the standards (1) • Documentation of all policies and procedures addressing all appropriate aspects of • operations and management (D5.1) • Detailed Standard Operating Procedure (SOP) Manual (readily available) (D5.2-3) • Followed by all personnel (D5.4) • Review (and training) of new/revised SOPs (documentation) (D5.5) • Archived procedures (D5.6) • SOPs shall comply with these Standards and all applicable governmental regulations • (D5.7)

  13. JACIE inspector training • D5 Policies and procedures: the standards (2) • D5.1 Written policies and procedures must include: • Product receipt • Processing and process control • Testing of red cell compatibility and processing of ABO-incompatible products • Labeling • Expiration dates • Storage (also alternative storage) • Release (and exceptional release) • Product tracking • Transportation • QM and improvement • Equipment and supplies • Maintenance and monitoring • Errors, accidents and averse events • Biological product deviations • Corrective actions • Personnel training • Competency assessment • Outcome analysis • Audits • Decontamination and disposal • Infection control and biosafety, chemical safety • Environment control • Cleaning and sanitation • Hygiene and personal protection • Facility management • Donor and patient confidentiality • Emergence and safety • Disaster plan

  14. JACIE inspector training • D5 Policies and procedures: the standards (3) • D5.2 • SOP of the SOP’s (preparation, reviewing, implementing and revision) • Standarised format (including worksheets, reports and forms) • System of numbering and titling • Content: • - Purpose • - Equipment and supplies • - Objectives and acceptable endpoints (range expected results) • - Stepwise description of the procedure (diagram and/or tables) • - Related SOP’s • - References (literature) • - Approval, modifications, annual review • - Expected results

  15. JACIE inspector training D5 Policies and procedures: the inspection • Content of SOP manual* • SOP’s related to specific prodedure • Readers list • Biannual review of SOP’s • SOP of the SOP’s* • Archivage of old SOP’s • * “at home”

  16. JACIE inspector training • D6 Process controls : the standards (1) • Written request (order form) from the recipients physician before processing is initiated • (D6.1) • Processing procedures: validation and documentation of acceptable viability and recovery • (D6.1) • Critical control points and associated assays (D6.2) • Aseptic technique (D6.2.1)

  17. JACIE inspector training • D6 Process controls : the standards (2) • Monitoring and documentation of microbial contamination (review, communication with • recipients physician) (D6.3.1-2) • Completed worksheets (responsible individual, lot numbers, expiry dates, maintained) • (D6.3.3) • Review of processing records prior to product release (D6.3.4) • Communication with recipients physician when clinically relevant processing end-points • are not met (D6.3.4.1) • ABO/Rh testing: for allogeneic products on each collected product; for autologous products • on the first collected product (comparison with last available test result; documentation of • discrepancies) (D6.4) • The establishment of appropriate and validated assays, and test procedures for the • evaluation of cellular therapy products (System for identification and handling of test sample; • aliquot(s) of the cryopreserved product stored under repesentative conditions (D6.5)

  18. JACIE inspector training D6 Process controls : the inspection • Completed order form, worksheet (patient file!) • Documentation and review microbiology tests • Validation data for assay for evaluating product

  19. JACIE inspector training • D7 Labels: the standards • Labeling operations (prevention of mislabeling, approved standard templates, control stocks) • (D7.1) • Information on container label shall be verified by at least two staff members (D7.1.2.3) • Product identification (unique numeric or aplhanumeric identifier, identifying multiple • containers for the same product) (D7.2) • Label content (partial label, biohazard label, during and after processing, prior to and • at distribution) (D7.3) • Accompanying documentation at or immediately after distribution (D7.3.7-8)

  20. JACIE inspector training D7 Labels: the inspection • Review prior to on-site visit !!! • Completed labels • Recipients

  21. JACIE inspector training • D8 Cellular product distribution: the standards • Review of processing and tracking (tracibility donor-recipient) records prior to distribution • (D8.1) • Release criteria (for each product) (D8.1.2) • Exceptional release approved by processing facility medical director (agreement with • recipient’s physician (documentation in processing record) (D8.1.2.1-2) • Inspection by two trained personnel immediately before release (labeling and integrity) • (D8.1.3) • Distribution records (date, name and unique identifier of recipient,...) (D8.2) • Circular of information (side effects, dosage and administratiorecommandations, • instructions for handling) (D8.3) • Return of cellular therapy products from issue (integrity not been compromised, maintained • at specified temperature, interaction with recipient’s physician regarding re-issue or disposal, • records) (D8.4)

  22. JACIE inspector training D8 Cellular product distribution: the inspection • Infusion instructions (different products)* • Completed infusion forms • Documentation of integrity check • SOP for return and re-issue* • Records of returned components • * “at home”

  23. JACIE inspector training • D9 Cellular therapy product storage: the standards • Policies and procedures to control storage areas and to prevent improper release of products • (D9.1) • Storage duration (also, storage conditions) (D9.2) • Storage temperature(D9.3) • Product safety (separated and specified area in recipient for quarantined products or products • with risk of cross-contamination (D9.4) • Monitoring (temperature: at least every 4 hours; system to ensure maintenance of • liquid nitrogen levels) (D9.5) • Alarm Systems (periodically checked, instructions in case storage device fails, additional • storage possibility) (D9.6) • Security (admittance restricted to authorized personnel) (D9.7) • Inventory Control system (D9.8)

  24. JACIE inspector training D9 Cellular therapy product storage: the inspection • Observe room and storage devices • Look for alarm system (regular checks) • Review inventory system • Ask personnel to locate a selected product • Storage of test aliquots • Instructions in case of device failure

  25. JACIE inspector training • D10 Receipt and transportation: the standards • Procedures (non-frozen and crypreserved products) (D10.1-2) • Non-frozen products: in secondary plastic bag (D10.3) • Outer shipping container (validated, controlled storage temperature, temperature monitor, • labelled) (D10.4) • Methods of transport: minimal transit time, qualified courier, alternative transport plans, • no X-ray control) (D10.5) • Transport records (tracing, identity of courier, delays or problems during transportation) • (D10.6)

  26. JACIE inspector training D10 Receipt and transportation: the inspection • Labelling of transport container • Validation report of transport container • Example of temperature registration curve • Observe transport container and temperature monitor • Example of transport record

  27. JACIE inspector training • D11 Disposal: the standards • Written policy (D11.1) • Written agreement between the donor, patient or recipient and storage facility • (length of storage and the circumstances for disposal) (D11.2) • Written documentation of patient death or reason of disposal (D11.3) • Records of discarded products (date, disposition, method of disposal)(D11.4) • Approval by Laboratory Director in consultation with the recipients physician (D11.5) • Method of disposal shall meet governmental regulations for disposal of biohazardous • materials and medical waste (D11.6)

  28. JACIE inspector training D11 Disposal: the inspection • Example of record of product disposal • Review SOP for disposal • (consistent with consent at collection?)

  29. JACIE inspector training • D12 Records: the standards • Records related to quality control, personnel training or competency, facility management, • general facility issues shall be retained for at least 10 years(D12.1). Records of cellular • products: 10 years after administration(D12.4) • General requirements (records management system to facilitate review and to ensure • prompt identification) (D12.2) • Electronic records (computer record-keeping system, back-up or alternative • system, periodically tested; SOP for record entry, verification and revision, limited access; • ability to generate true copies; validation of system; training in use; SOP for system • maintenance,...) (D12.3) • Records in case of divided responsibility (system to exchange information) (D12.5)

  30. JACIE inspector training D12 Records: the inspection • Review SOP record storage • Ask to select all records related to one particular • patient • Ask to see stored records • Demonstration of data base

  31. Processing Facility – Most Common and Important Deficiencies • D5 Policies and procedures • D7.3 Labels – information contained, usage • D6.10 “For allogeneic products a test for the ABO group and Rh type shall be performed on the first product or on blood obtained from the donor at the time of the first collection”

  32. Policies and Procedures • Document control system inadequate • Specific policies missing e.g. storage, transportation • Lack or approval or regular review • Format incorrect, no range of expected results or acceptable endpoints • No references given • No examples of associated worksheets or forms • No documented training to new/revised SOPs

  33. LABELS • Example labels not appended to SOP • SOP to include Biohazard label • Pre- or demand printed labels • HPC,Apheresis • Name + volume of AC or additives not stated

  34. Corrective actions • B4.10 – “corrective action shall be implemented as appropriate” • Deficiencies recorded – lack of audit audit not regular critical endpoints not defined not disseminated • Adverse events and clinical incidents not reported/recorded; absence of corrective actions

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