Sharon Tindle, MS, CQA (ASQ) QA Manager, BMT Tissue Services Mount Sinai Hospital, New York, NY. June 7, 2016

Transcription

1 Sharon Tindle, MS, CQA (ASQ) QA Manager, BMT Tissue Services Mount Sinai Hospital, New York, NY June 7,

2 Brief description of the Mount Sinai Cellular Therapy Laboratory Overview of BM transplant process History of BM transplants Regulatory timeline Quality essentials comparison 2

3 Hospital-based laboratory Regulatory status: Registered with FDA Licensed by New York State Department of Health Accredited by AABB and FACT 3

4 Donors Allogeneic (related and unrelated) Autologous Processing and freezing for long-term storage (autologous) Patient receives high-dose chemotherapy Transplant Immediate (allogeneic) Delayed (autologous) 4

5 Source of cells Bone marrow Apheresis (peripheral blood mobilized from the marrow by administering growth factors alone or in combination with chemotherapy) Umbilical cord blood 5

6 Centrifuge Freeze Store in Liquid Nitrogen Thaw for Infusion Cells Donor Recipient 6

7 First successful BM transplant between a leukemia patient and a related donor (identical twin) performed in New York First BM transplant for non-cancer treatment between a severe combined immunodeficiency syndrome (SCID) patient and a related donor (matched sister) First BM transplant between SCID patient and unrelated donor 1981 First successful autologous PBSC transplants First successful UCB transplants First successful allogeneic PBSC transplants 1950s 1960s 1970s 1980s 1990s IBMTR established to monitor and study outcomes of bone marrow transplants The National Bone Marrow Donor Registry was federally funded 1988 U.S. Organ Transplant Amendments Act mandated collecting donor and recipient outcome data 7

8 1970 FDA Public Health Service Act of 1944 modified to include blood, blood components, and derivatives, leading to licensing of blood banks FDA draft documents concerning the regulation of UCB and PBSC products intended for transplantation 1998 FDA Proposed rule for Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) establishment registration (Final rule published 2001, 21 CFR Part 1271, Subparts A and B) 1999 FDA Proposed rule for suitability determination for donors of HCT/Ps (Final rule published 2004, effective date May 2005, 21 CFR Part 1271, Subpart C) 1940s 1970s 1990s 1958 AABB Standards for Blood Banks and Transfusion Services (BBTS), 1st Edition AABB BBTS Standards, 14th Edition, includes BM processing requirements 1996 AABB Standards for Hematopoietic Progenitor Cells, 1st Edition 1996 FACT Standards for Hematopoietic Progenitor Cell Collection, Processing and Transplantation, 1st Edition 8

9 NY State DOH licensing required for tissue banks 2001 FDA Proposed rule for current good tissue practice for manufacturers of HCT/Ps (Final rule published 2004, effective date May 2005, 21 CFR Part 1271, Subparts D, E, and F) 2004 NY State DOH Hematopoietic Progenitor Cell Banks standards and requirements Various FDA revisions and guidance documents related to HCT/Ps 2005 FDA Final rule, 21 CFR Part 1271 in effect NetCord-FACT International Standards for Cord Blood Collection, Banking, and Release for Administration, 1st Edition 2001 AABB Standards for Cord Blood Services, 1st Edition 2004 AABB Standards for Cellular Therapy Product Services, 1st Edition (HPC and CB Standards merged) 2006 FACT-JACIE International Standards for Cellular Therapy Product Collection, Processing and Administration, 3rd Edition AABB Standards for Cellular Therapy Product Services, 6th Edition, includes clinical activities FACT Common Standards for Cellular Therapies (manipulated cells for regenerative medicine) 9

10 FDA 21 CFR Part : You must establish and maintain a quality program intended to prevent the introduction, transmission, or spread of communicable diseases through the manufacture and use of HCT/Ps. The quality program must address all core CGTP requirements listed in Sec (b). Facilities Environmental control Processing and process controls Receipt, pre-distribution shipment, and distribution Donor eligibility determinations, screening, and testing Equipment Labeling controls Supplies and reagents Storage Recovery 10

11 AABB 1.2.2: The facility shall establish and maintain a quality system to ensure that activities related to donor and patient care as well as the procurement, processing, storage, testing, distribution, administration, and post-administration monitoring of cellular therapies conform to specified requirements. Organization Resources Equipment Agreements Process control Documents and records Deviations, nonconforming products or services, and adverse events Internal and external assessments Process improvement Safety and facilities 11

12 FACT: The Clinical Program (B4.2) / Collection Facility (C4.2) / Processing Facility (D4.2) shall establish and maintain a written Quality Management Plan that addresses, at a minimum: Organizational structure Audits Personnel qualifications, training, and competency Product tracking Document control Interrupted facility operations Agreements Outcome analysis Validation of procedures Management of cellular therapy products with positive microbial culture results Detection and reporting of errors, accidents, and adverse events Qualification of reagents, supplies, equipment, manufacturers, vendors, and facilities 12

13 ISO Quality Management Principles FDA AABB FACT QMP 1 Customer focus 1. Donor eligibility determinations, screening, and testing QMP 2 Leadership Organization Organizational structure QMP 3 Engagement of people Resources Personnel QMP 4 Process approach 1. Processing and process controls 2. Supplies and reagents 3. Equipment 4. Recovery 5. Receipt, pre-distribution shipment, and distribution 6. Labeling controls 7. Storage 8. Facilities 9. Environmental control 1. Process control 2. Documents and records 3. Equipment 4. Safety and facilities QMP 5 Improvement 1. Deviations, nonconforming products or services, and adverse events 2. Internal and external assessments 3. Process improvement QMP 6 Evidence-based decision making QMP 7 Relationship management Agreements Agreements 1. Document control Product tracking 2. Validation of procedures 3. Qualification of reagents, supplies, equipment, manufacturers, vendors, and facilities 4. Interrupted facility operations 1. Detection and reporting of errors, accidents, and adverse events 2. Management of cellular therapy products with positive microbial culture results 3. Audits Outcome analysis 13

14 Thank you! 14