Quality Medical and Laboratory Practice in Cellular Therapy

Quality Plans: Development and Implementation ISCT Annual Meeting May 24, 2010 Lizette Caballero, B.S., M.T.(ASCP) Laboratory Manager Florida Hospital Cellular Therapy Laboratory

Quality Plan: Development and Implementation Show hands How many attendees work for: Clinical Program Collection Facility Processing Facility

OBJECTIVES Discussion of quality management goals and structure. Share my experience on how we developed a quality plan. Describe deficiencies related to the quality management section and provide tools/ideas to avoid them.

Goals of Quality Management Ensure credibility of outcomes Improve patient safety and quality of processes Significantly reduce errors Quality Medical and Laboratory Practice in Cellular Therapy Emphasize measures to investigate, detect, assess, correct, and prevent errors Catherine Bollard, MD, FACT Quality Management Webinar

Quality Management Program The Quality Management Program can be related to the institutional program in several ways, including: Institutional Program Institutional SOPs Applicant QM Plan Institutional QM Program Program QM Program Applicant- Specific SOPs Nested within the Institutional QM Program Program Shared components QM with Program the Institutional QM Program Institutional QM Program Program QM Program Completely separate from the QM Program Catherine Bollard, MD, FACT Quality Management Webinar

QM Plan vs Policies vs Procedures Quality Management Plan Example: There is a system for detecting, evaluating, documenting, and reporting errors, accidents, suspected adverse events, biological product deviations and complaints. Policies All incidents, deviations, errors, and unusual occurrences in the transplant program that affect the quality of patient care should be reported, analyzed and corrected. Procedures 1. Document complaints or deviations from errors. 2. Investigate, track and analyze. 3. Determine corrective action and follow up.

Elements of a Quality Management Plan 1. Structural Requirements Responsibility for QM program, organizational chart, personnel requirements, process for development and implementation of processes, policies, and procedures. 2. Assessment and Reporting Outcome analysis, audits, validations, and qualifications, evaluation of competency and proficiency, management of cellular products with positive microbial results, system for detection, evaluation, and reporting of accidents, errors, and adverse events. 3. Information and Document Control Mechanism for document control, process for product tracking, mechanisms to ensure continuous operations when information technology fails. Catherine Bollard, MD, FACT Quality Management Webinar

Location Overview of Our Program Clinic and Cellular Therapy Lab CTL BMT Unit (3rd Floor)

Transplant Program Structure Out Patient Clinic (FCCT) Staffed by FPMG (Florida Physician Management Group) In Patient Unit (BMTU)- 16 Beds Staffed by Florida Hospital Cellular Therapy Laboratory (CTL) Staffed by Florida Hospital Collection Facility Outsourced to Florida s Blood Centers (FBC)

HOW WE DID IT!!

Quality Program Development: How we did it Team Quality Manager Processing Laboratory Manager Program Director Office Manager (Clinic) BMT Unit Nurse Manager Quality Plan developed following FACT standards D4. Quality Plan shared by Out Patient, In Patient Clinic and Processing Laboratory- 28 pages.

Hematopoietic Progenitor Cell Transplant Program 0816.v4 Orlando, Florida Title: Transplant Program Quality Management Plan 1. PRINCIPLE: 1.1. Quality improvement is driven by the requirements of regulatory and accrediting agencies. This quality system conforms to the requirements of the FDA, FACT, NMDP, CIBMTR, JCAHO, CAP, CLIA, ASHI, and other accrediting organizations. The policies of the quality system are described in greater detail within this document and within the departments comprising the Transplant Program. Departments of the Transplant Program include: Florida Center for Cellular Therapy (FCCT), Florida Hospital Cancer Institute Cellular Therapy Lab (CTL), and Florida Hospital BMT Unit. 2. PURPOSE: 2.1. The purpose of the Quality Management Program is to constantly verify and improve the quality of services. We promote effective and efficient utilization by focusing on the analysis of patterns and trends in performances as they relate to clinicians needs and patient outcomes. 3. SCOPE: 3.1. This Quality Management Program incorporates information from clinical and processing areas. The contracted apheresis collection facility s quality activities are reflected in their Quality Management Plan.

Quality Program Development: How we did it What to do when writing a Quality Plan: Summarize and reference policies and procedures. Example: D4.5.1 The Quality Management Plan shall include or summarize and reference, a system for document control.

Hematopoietic Progenitor Cell Transplant Program 0816.v4 Orlando, Florida Title: Transplant Program Quality Management Plan 1. RECORD REVIEW AND DOCUMENT CONTROL: There is a mechanism in place for document control and for regular review of records relating to cellular therapy product processing, storage, release, transportation, transplantation, and product infusion. 1.1. The following is the current list of all critical documents that adhere to document control system requirements: 1.1.1. SOPs 1.1.2. Forms 1.1.3. Worksheets 1.1.4. Validation Plans 1.1.5. Consent Forms 1.1.6. Standing Orders 1.2. Refer to FH/FCCT SOP #0800 Instructions for Preparing, Implementing, and Reviewing Standard Operating Policies and/or Procedures and Associated Forms for the Clinical Program and CTL SOP #193.416 Policy for Preparing, Implementing and Reviewing SOPs and Associated Forms require the following elements: 1.2.1. A numeric or alphanumeric identifier is assigned to each documented within the system. 1.2.2. Signature of the Approving Individual, the Approval Date, and the Effective Date. 1.2.3. Protection to prevent documents undergoing accidental or unauthorized modification. 1.2.4. Documentation of training associated with each SOP release and revision.

Quality Program Development: How we do it Working with an outsource service (Collection Facility). How do we maintain communication and follow standards? Written agreement including role and responsibilities. Communication between Collection/Clinic/CTL. Packet with donor eligibility, current H&P, signed consents, verification of line placement, vein assessment, lab work and apheresis order is given to collection staff on the first day of collection.

Quality Program Development: How we do it Communication (Cont d) A report is generated and sent to FBC with data from each collection. The report is reviewed and signed by the FBC medical director and a copy is faxed back to CTL.

Donor Name: MRI# Recipient Weight (Kg): CD 34 Cell Dose (Total) Requested (X10 6 /kg): Machine Serial Number: Peripheral Blood WBC (X10 6 /ml) Hgb% Platelet (X10 6 /ml) CD34% CD34/uL Date: Date: Date: Date: Date: Day Number Day Number Day Number Day Number Day Number Pre Post Pre Post Pre Post Pre Post Pre Post Product Information Unique Identifier Product Volume (mls) WBC (X10 6 /ml) HCT% Gran% MNC% CD34% CD34 Dose(X10 6 /kg) CD34 Collection Efficiency (%) QC Information Day Number Was Efficiency Yield greater than 20% each day? Was total CD34 dose obtained? Product(s) Satisfactory for infusion (pending microbiology results) Day Number Day Number Day Number YES YES NO NO Day Number YES NO If NO Identify Product and give reason: Review Information: Processing Facility Collection Facility Lab Director/Designee Signature Date Medical Director/Designee Signature Date Print Name Please Fax back to the CTL after review 407-303-2441 Print Name Form 193.488Av.1(10/24/2008) FBC Colelction Data Sheet Page 1 of 1

Quality Program Development: How we do it Communication (Cont d) Collection Facility staff attend weekly meetings where upcoming collections are discussed. Collection Facility Medical Director attends monthly QA meetings. Positive Culture report is sent to collection facility medical director for review and signature.

Quality Program Function Outline Process improvement team: Monthly QA/QI Meetings (Collection and Lab representative present) Policy review committees Daily Inpatient Unit rounds. Weekly Patient Management Meeting (upcoming transplants). Weekly outpatient clinic patient review. Weekly Cellular Therapy Lab meeting with Medical Director. Bi-weekly Multi-disciplinary Tumor board meeting. Monthly FBC/FCCT Directors Meeting.

Processing Citations D10 7% D6 10% Other D8 4% 5% D4 28% Quality Management Section D5 10% D9 10% D7 12% D2 14% FACT Quality Management Webinar

Quality Management Citations in Processing Inspections Positive microbial culture results (D4.9) Include, or summarize and reference, such results in the QM Plan Be sure all required elements are addressed Be specific If treated as a variance: The procedures must specify this All required elements in D4.9 must be included Perform procedure adequately Superficial investigation, documentation, and reporting does not address the problem

Hematopoietic Progenitor Cell Transplant Program 0816.v4 Orlando, Florida Title: Transplant Program Quality Management Plan 1.1.1. leadership to be monitored, such as blood transfusions, falls, patient satisfaction, chemotherapy administration, and pain management. 2. MANAGEMENT OF CELLULAR THERAPY PRODUCTS WITH POSITIVE MICROBIAL CULTURE RESULTS: 2.1. All bacterial and fungal contamination of HPC-A, HPC-M, and TC-T products is monitored and documented. Microbiology reports and contamination documentation is kept in the CTL patients file. Contaminated products are reviewed quarterly by the QA/QI Committee. Trends are identified and an action plan formulated. The Manager of the Cellular Therapy Laboratory presents a report for review and discussion quarterly, or sooner, as applicable. Refer to CTL SOP #193.431 Guidelines for the Management of Culture Positive Component 2.2. Documentation and product labeling Refer to CTL SOP #193.463 Labeling of HPC 2.3. Release of the product from the distribution facility, including identification of authorized individuals and criteria for produce release. Refer to CTL SOP #193.491 Product Release Criteria 2.4. Investigation of cause- Refer to CTL SOP #193.454 Errors/Unusual Occurrence Reporting and Management 2.5. Notification of transplant physician, collection facility and/or Cell Process Facility as applicable- Refer to CTL SOP #193.431 Guidelines for the Management of Culture Positive Component 2.6. Notification of the recipient prior to infusion Refer to FH/FCCT SOP #0810 Allogeneic Hematopoietic Progenitor Cell (HPC) Recipient Evaluation and SOP #0813 Autologous Hematopoietic Progenitor Cell (HPC) Recipient Evaluation and Selection. 2.7. Recipient follow-up and outcome analysis Refer to FH/FCCT SOP #0810 Allogeneic Hematopoietic Progenitor Cell (HPC) Recipient Evaluation and Selection and SOP #0813 Autologous Hematopoietic Progenitor Cell (HPC) Recipient Evaluation and Selection.

Quality Management Citations in Processing Inspections Validation Must be included, or summarized or referenced, in the QM Plan. Even if a procedure has been in use for years, it still needs to be validated and/or verified. Documentation must be available to the inspector. Review and acceptance of validation studies must be documented by appropriate individual from Quality Management.

Hematopoietic Progenitor Cell Transplant Program 0816.v4 Orlando, Florida Title: Transplant Program Quality Management Plan 1.1.1. specifications. Results of all such test and procedures become part of the permanent records of the product processed. 1.1.2. Communicable disease testing is performed using FDA approved tests in an FDA registered laboratory that is accredited and licensed in accordance with applicable governmental regulations. 1.1.3. All other tests, not performed by the Processing Facility, are performed by a laboratory certified by CLIA. 1.1.4. For tests performed within the Processing Facility, there is documentation of ongoing proficiency testing as designated by the Processing Facility Director. The results are reviewed by the Processing Facility Director or designee and outcomes reviewed with the staff. 1.1.5. Cellular therapy products that do not meet release or donor-eligibility requirements are distributed only if there is documented urgent medical need for the product. Documentation includes, at a minimum, the approval of the recipient s physician and the Processing Facility Medical Director or other designated physician. 1.1.5.1. Notification of the recipient s physician of testing and screening results for ineligible donors is documented. 2. VALIDATION AND QUALIFICATION OF CRITICAL REAGENTS, EQUIPMENT, AND PROCEDURES: 2.1. There is a process in use for validating and verifying all reagents, equipment, and procedures refer to CTL SOP# 193.493 Validation Equipment, Process or Procedure. 2.1.1. The Program Director and the Quality Assurance Manager review and approve all validation studies. 2.1.2. Changes to a process are verified or validated to ensure that they do not create an adverse impact anywhere in the operation.

FHCI Cellular Therapy Laboratory 2501 North Orange Ave. Suite 786 Orlando, FL 32804 Validation Plan VALIDATION TITLE: Retrospective Analysis of Allogeneic Bone Marrow Collections Validation of: Equipment Process Product (Check all that apply) Type: (IQ) Installation Qualification (OQ) Operation Qualification (PQ) Performance Qualification I. PURPOSE OF VALIDATION This validation will provide a retrospective review of the allogeneic bone marrow collections performed by the bone marrow collection facility at Florida Hospital to establish acceptable ranges for MNC, TNC, sterility, and viability based on the data collected. II. SYSTEM DESCRIPTION Allogeneic bone marrow harvests performed by the physicians and physician s assistants (P.A.) of the bone marrow collection facility at Florida Hospital will be evaluated for total MNC, total TNC, MNC/kg (recipient), TNC/kg (recipient), sterility, volume (ml/kg recipient) and viability of the product collected. Engraftment data will be analyzed to determine successful outcome. This retrospective analysis will be used to establish acceptable ranges for future allogeneic bone marrow harvests. III. RESPONSIBILITY ASSIGNMENT- Document name in table (Signatures follow plan and results). Validation Plan written by (manager): Validation Plan reviewed by (facility director): Validation Plan approved by (medical director): Susan Ingersoll, Ph.D./Lizette Caballero, MT (ASCP) John R. Edwards, M.D. Vijay Reddy, M.D., Ph.D. Validation performed by (staff): Validation Results evaluated by (manager): Validation Results reviewed by (facility director): Validation Results approved by (medical director): Susan Ingersoll, Anginett Batista, Lizette Caballero Susan Ingersoll, Ph.D./Lizette Caballero, MT (ASCP) John R. Edwards, M.D. Vijay Reddy, M.D., Ph.D. IV. VALIDATION PLAN A. List SOPs, personnel, equipment, and supplies required.

Quality Management Citations in Processing Inspections The Quality management Plan shall include, or summarize and reference, policies and procedures and a timetable for conducting and reviewing audits of the processing Facility s activities Results of the audits shall be used to recognize problems, detect trends and identify improvement opportunities.

Audit of Product Processing, Distribution & Infusion Records FHCI Cellular Therapy Lab, 2501 North Orange Ave. Ste. 786 Orlando, FL 32804 Recipient Name Donor Name Product Name Recipient ID Donor Patient ID Collection Date Instructions: Review the forms listed below that may be completed in association with product processing or infusion for accuracy and/or completeness, then mark as Acceptable or Unacceptable. If Unacceptable, please list comment # and comment. Write N/A if not applicable. PROCESSING DOCUMENTATION Donor Infec Dx Mark testing 30 days of HPC or 7days of TC-T collect or labeled w/ Warning labels Donor History Questionnaire completed and signed by donor and person obtaining consent Consent for Mobilization and Collection & Storage and Discard of HPC signed Consent for Treatment signed Donor Eligibility Form completed with test results and signed by Medical Director and Transplant physician Final Declaration of Donor Eligibility completed and signed by Medical Director and Transplant Physician HPC Processing Order Form signed by the requesting MD Collection Data Sheet from day of collection (from FBC) in the chart Daily QC performed on each day of processing Do the product modifications ordered on the HPC Processing Order form was performed? Component Control Record completed for each product Daily Cell counts Printouts Donor/recipient collection date ABO/Rh compared to previous typing for consistency (daily) Audit Tool Accurate Y or N Complete Y or N Acceptable Check Unacceptable Check Comment Number

FHCI Cellular Therapy Laboratory 2501 North Orange Ave. Suite 786 Orlando, FL 32804 Audit Results Audit TITLE: Audit of Product Processing, Distribution and Infusion Records Audit NUMBER:A010 Audit of: Equipment X Process Product Label Form I. PURPOSE OF AUDIT Forms and records associated with product processing or infusion will be checked for accuracy and/or completeness. II. SYSTEM DESCRIPTION Patient s chart will be reviewed following checklist form 193.470B. Unacceptable finding will be described in the comments section. Ach audit will be reviewed by the Quality Assurance Representative and Medical Director. III. RESPONSIBILITY ASSIGNMENT- Document name in table (Signatures follow plan and results). Audited by: Audit Results evaluated by: Audit Results reviewed by: Quality Management review by: A. Establish the number of test samples required. 3 patient s charts Audit Report B. Describe Audit Results (if no corrective action/process improvement is required proceed to step VI). 3 out of 3 records were completed and accurate. C. Determine data/records to be collected to fix findings (if applicable). D. Establish corrective actions or process improvement to be made as a result of this audit. IV. Establish expected date of completion of the corrective action V. Establish expected date to re-audit to verify that the corrective actions were effective. VI. CONCLUSION A. Determination of acceptance for audit/corrective action findings: B. The following department(s) and personnel were informed of findings: VIII. AUDIT RESULTS AND FOLLOW UP (IF APPLICABLE) SIGNATURES Laboratory Supervisor: Medical Director: Quality Assurance: Date: Date: Date: Corrective Action Results approved: N/A YES NO (if not approved, attach revised plan.)

HOW THE TEAM FELT!

Roadblocks to Success Poor Communication Difficulties trying to get the team together. Too many meetings. Lack of Understanding What is a Quality Plan? Why we need one? Why we need SOPs? I know we do it; why do I need to document? Minimal or Non Staff Engagement Think, talk, look for quality in everything you do. Non-clinical personnel. Resistance to Change in Culture Non punitive to process improvement mentality. Encouragement to report mistakes and close calls.

Acknowledgement Cellular Therapy Laboratory Anginett Batista Joanne Sullivan Teshia Wright FACT

Q & A Session Collection How do centers avoid ineligible donors due to pending testing? How do centers come up with release criteria for their products? Collection Facility Processing Facility What is required to be qualified as a trainer at your institution? Give examples of audits at your institution? How often? What is the process for analysis of audits and identification of areas for improvement? Processing Who was part of the team during the development of your QMP? How do you communicate with other departments when something fails? Release criteria not achieved, adverse reaction, etc. How do you document this communication?