PACT Web Seminar July 19, 2007



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PACT Web Seminar July 19, 2007 Phyllis I. Warkentin, MD Professor, Pathology and Pediatrics University of NE Medical Center Medical Director Chairman, Accreditation Program Foundation for the Accreditation of Cellular Therapy (FACT)

PACT Web Seminar July 19, 2007 Audience survey FACT, FACT-JACIE, and NetCord- FACT Standards and Accreditation AABB Standards and Accreditation Standards harmonization Questions

Inspection & Accreditation FACT, JACIE and NetCord Standards Development, changes Accreditation Overview Processes Outcomes Major challenges

Foundation for the Accreditation of Cellular Therapy Founded by: American Society for Blood and Marrow Transplant International Society for Cellular Therapy Purposes: Establish standards for quality medical and laboratory practice Implement voluntary inspection and accreditation program

Joint Accreditation Committee EBMT- ISCT (JACIE) Established 1999 Adopted FACT Standards 1999 Joint inspector training 2000, 2001, 2002 Joint review of 2002 FACT Standards (2nd Ed) Joint development of 3rd Edition Standards 2006 Countries participating: Austria The Netherlands Belgium Spain Denmark Sweden Finland Switzerland France United Kingdom Germany Italy Norway

FACT-JACIE International Standards Scope and Content Standards apply to: Hematopoietic progenitor cells from any tissue source Therapeutic cells (nucleated cells other than HPC) Cover all phases of collection, processing, and administration (excluding collection and banking of cord blood cells) Require all clinical, collection, and laboratory facilities to: Develop and maintain a comprehensive Quality Management Program Evaluate and report outcomes Comply with Applicable Law

Cord Blood Bank Standards and Accreditation 1996: FACT Standards for Hematopoietic Progenitor Cells 2000: International Standards for Cord Blood Banking 2002: International Inspection and Accreditation Program started 2006: Third Edition of Standards published

NetCord-FACT Standards: Scope and Content Cover all phases of cord blood collection, processing, testing, banking, selection, release Require all cord blood banks to: Maintain comprehensive Quality Management Program Utilize validated methods, supplies, reagents, equipment Maintain product tracking Maintain details of clinical outcome Comply with Applicable Law CBB must have a process to address every Standard

Standards Development Standards Committee Chairman Subcommittees for Cellular Therapy Product Standards: Clinical Collection (marrow and peripheral blood cells) Cell processing laboratory Subcommittees for Cord Blood Banking: Collection Processing Banking Committee members: Volunteer experts, experienced inspectors Leadership and membership roles for FACT and JACIE Liaisons from NMDP, other interested parties Three-year staggered revision cycle

Standards Development New/revised Standards proposed by membership of parent organizations, inspectorate, accredited programs, others based on: New evidence, regulations, or standards of care Standards drafted by subcommittees, reviewed by oversight committee, legal counsel, Boards, and published for member / public comment Each comment received, considered, and resolved Standards revised; approved by Boards, published Effective 90 days from publication

CTP and CBB Standards Third Editions - Major Changes Regulatory requirements (FDA, EU Directive) Label Tables including Biohazard and Warnings Core GTP, donor eligibility, documentation requirements Incorporate recommendation for ISBT128 terminology and labeling

ISBT 128 The international information technology standard for transfusion medicine and transplantation International Technical Advisory Group established representing interested organizations, coordinated by ICCBBA, Inc. to: review existing regulation regarding labeling; design product label templates that satisfy regulatory requirements; provide a focus for the standardization of terminology and product naming; promote the adoption of the ISBT 128 standard in cellular therapy facilities around the world; provide advice and support to facilities introducing the standard; advise on the ongoing development of the ISBT 128 standard to support new developments in cellular therapy. Publications: Transfusion, July 2007. Recommendations for terminology, label design, and implementation.

FACT-JACIE International Standards Third Edition - Significant Changes Restructured document to make sections parallel (Clinical, Collection, and Laboratory) Expanded quality management throughout Added requirements re: radiation therapy Redefined numbers requirements: Clinical - reduced number of autologous transplants Collection and Laboratory minimum numbers added for procedures / time Expanded requirements for pediatric competencies clinical and collection

NetCord-FACT International Standards Third Edition Major Changes Quality Management consolidated Specific, detailed; applies to all CBB facilities Specific Standards for Directed (related) CB Donations autologous or allogeneic Most Standards are the same Specific Standards for transfer of inventories, cessation of activities Lower storage temperature requirement [= -150 C]

Accreditation Process

FACT Inspection /Accreditation Voluntary accreditation Scheduled inspections Educational, collegial, helpful inspections Basis for accreditation: Compliance with Standards Written application and on-site inspection Central office preview and review Volunteer inspectors, expert in the field Inspection Team sufficient in size and expertise, based on the size and complexity of the applicant Results are not left on-site Accreditation Committee review; determines next steps and accreditation status of each applicant. Results & appeals to Boards

FACT Inspection / Accreditation ** D D D D APPLICANT Y N N/A INSPECTOR Y N N/A Checklist documentation Focus on Standards Facility answers each item; inspectors verify Promote consistency and completeness Checklist design Questions taken directly from each Standard Some redundancy Permits flexibility in program structure and inspector assignments

FACT and JACIE Accreditation FACT Accreditation - US and Canada; Australia - 2007 Australian Therapeutic Goods Administration adopted Collection and Laboratory FACT Standards (2 nd ed) Clinical Standards outside purview of the TGA Children s Oncology Group - FACT Accreditation JACIE Standards identical (joint); accreditation separate Accreditation process similar to FACT, not identical In language of the applicant More dependence on individual/regional inspectors

FACT / NetCord Accreditation Single accreditation for cord blood banks worldwide International teams include team leader, collection site inspector(s) and laboratory inspector All cord blood banks eligible Must have mechanisms in place to meet all Standards Two days minimum; scheduled inspections Visit all sites, proportion of collection sites Observe variable collection, transport, and storage

FACT Accreditation Program Facility Eligibility Clinical Transplantation Program Cellular Product Collection Facility Cellular Product Processing Facility No specific program structure is required Functional coordination/cooperation required Clinical Program must utilize a collection service and a cell processing laboratory that meet FACT Standards: FACT - accredited Successfully inspected without accreditation Accredited programs submit annual reports; notify FACT of major changes

FACT Accreditation July 2007 First accredited programs in in North America: March 1998 HPC Facilities registered 183 (~92%) ACCREDITED 153 (US and Canada) HPC Renewal Accreditation 115 programs

FACT-NetCord Cord Blood Bank Accreditation July 2007 CBB Applicants 54 (US, UK, Europe, Asia) ACCREDITED 15 Non-US 10 Additional inspected 6 Non-US 3

Entities Requesting Information About FACT Accreditation States MA, KY, OK (Medicaid), Minnesota (DHS) Cooperative Groups CTN, SWOG, ECOG, COG Payers Aetna, Allianz AG (Lifetrack), BC/BS, First Health, Humana, Pacificare, URN

Most Common Deficiencies Third Edition 2006 Elements of Quality Management missing: Activity being performed, not in QMP Activity not being performed, in QMP Activity not mentioned and not performed

Top 10 Deficiencies 6. Required elements missing from labels at the end of processing or at distribution (laboratory) RBC compatibility, proper name of product, volume of anticoagulants / additives, expiration date and time, unique identifier of product 7. Insufficient clinical SOPs Outcome analysis, personnel training/competency, errors, accidents, adverse reactions, transportation, donor evaluation/selection, audits 8. Missing QM elements in processing lab Validation of processes, equipment; qualification of reagents 9. No documentation of director review of SOPs or records in collection Records pertinent to collected product not reviewed 10. Collection worksheets not in SOPs, no document control, not completed (Third edition does not require correctly completed examples)

Top 10 Deficiencies 1. Failure to have written SOPs for all aspects of the collection operation Labeling, Transportation, corrective actions, expiration dates, personnel training, competency, storage 2. Failure to have validation of significant processes and equipment in collection Collection process, equipment, reagents, labels, computers 3. Elements of collection QM missing Validations, outcome parameters, audits, corrective action, oversight of donor care (errors, accidents, adverse events) 4. Failure to have written SOPs for all aspects of the processing laboratory Labeling, safety, expiration dates, cleaning, biological product deviations, audits, corrective action, competency documentation, personnel training 5. Errors in data management - clinical

Top 10 CBB Deficiencies 6. Insufficient staff for the operation Processing, collection, outcome analysis 7. Quality program deficiencies: QM elements missing Bank, lab, collection sites QMP not integrated No / infrequent communication with collection sites, no feed-back 8. Label elements missing 9. SOPs not reviewed annually 10. Alarmed areas lack instructions for response

Top 10 CBB Deficiencies 1. SOP deficiencies: Incomplete, unclear, imprecise work instructions; responsible persons not identified; equivalent without further explanation; missing for some operations 2. Staff review &/or training of new/revised procedures not documented Laboratory and collection staff 3. Inadequate training of collection staff 4. Inadequate segregation / identification of designated (directed donor) units 5. Processing: technical errors Product bags not are examined before or after filling Labels, seals, welds not examined

Questions? www.factwebsite.org pwarkent@unmc.edu lmiller1@unmc.edu

JACIE Accreditation July 2007 HPC Facilities registered 90 12 Countries ACCREDITED 38 Australia, Finland, France, Italy, Netherlands, United Kingdom, Switzerland