QA:1.6
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Implementation date: 10/15/07 Obsolete date: QA Initials:
Review dates:
Revision dates: 01/16/0910/07/09
QUALITY ASSURANCE PROGRAM
PRINCIPLE:
The … Facility . performs various steps in the manufacture of human cells, tissue and tissue-based products (HCT/Ps)and maintains a detailed Quality Assurance Program (QA Program hereafter). The QA Program specifically focuses onFACT-JACIE International Standards for Cellular Therapy Product Collection, Processing and Administration and the FDA’s 21 CFR1271 (cGTP) guidelines. The overall goal of the QA Program is toprevent the introduction, transmission, or spread of communicable diseases through the manufacturing and use of HCT/Ps and to assure HCT/Ps have the required safety, purity, potency and effectiveness.
…’sQuality Plan identifies and monitors specific operational systems in the QA Program. The Program is an integral part of the BMTTotal Quality Management (TQM) Program. QA monitors implemented systems to ensure the goals and objectives are consistent with the Program as well as University. The QA Program ensuresintegration and participation with the BMT and all other contracted clientquality programs.
Facility Mission Statement:
Consistently provide high quality stem and progenitor cells for target disease treatmentsand novelcell-based therapies.
PURPOSE:
Outline the Quality Plan, including key personnel and procedures integral to Quality Assurance
SCOPE:
The QA Program is designed to encompass all aspects of operations. The Quality Manager, QA Supervisor,Technical Supervisor/Manager and Lab Director will ensure it’s adherence throughout all laboratory activities.
SPECIMEN REQUIREMENTS: N/A
REAGENTS, STANDARDS, MEDIA, AND SPECIAL SUPPLIES REQUIRED: N/A
INSTRUMENTATION:
Personal Computer loaded with Q-Pulse Quality Management System
FORMS, WORKSHEETS AND LABELS: N/A
CALIBRATION: N/A
CONTROLS: N/A
PROCEDURE:
- Quality Assurance Program-- The QA Program establishes and maintains ongoing, systematic monitoring for critical lab processes, procedures and equipment. It also identifies and resolves problems in a productive and timely manner. Program elements:
1.Organizational Structure – (see ATTACHMENT 1)
a.Organization chart indicates key personnel and the reporting structure
b.Processing/Collections Facility Director: Responsible for QA Program as it pertains to the facility
1)Director designates Quality Assurance Managerto establish and maintainthe QA Program
a)Manager works with QA department staff to perform all program aspects
(1)QA staff may not quality review their own tasks performed
b)QA Manager (with Technical Manager) assign QA responsibilities to ...staff as needed
c)QA compiles qualitydata and reports the results to...,all program BMT and (quarterly minimum)
2)Director and QA determinemonitored indicators requiring audits
3)Director, QA Manager and/or BMT Program Director work together on corrective/preventive action (CAPA) and follow up as needed
c.Designees assigned in the order listed:
1)Director
a)General: Technical Manager serves as designee when Director is not available
b)Infusion orders/medical orders/Urgent Medical Need: Technical Manager, Technical Supervisor, Apheresis Supervisor, Lead Stem Cell Technologist, QA Supervisor
c)QA Functions (Planned Deviations): QA Manager, QA Supervisor
2)Technical Manager
a)General: Technical Supervisor/Lead Stem Cell Technologist
b)Chart Review: Apheresis Supervisor, Technical Supervisor/Lead Stem Cell Technologist, QA Supervisor
3)QA Manager
a)General: QA Supervisor
4)Regenerative Medicine (RM) Project Development Manager
a)General: RM Supervisor, Lead RM Technologist
5)RM Supervisor
a)General: Lead RM Technologist
- Related SOPs/documents:
Job Descriptions for positions noted above
Annual Quality Indicator Review
Annual QA Summary
Organizational Chart
2.Personnel
a.Staff Training and Competency binder in the Program Coordinator’s office includes:
1)Current Job Description for all facility positions (also describes initial qualifications)
2)Orientation and initial facility training and re-training if applicable
a)Includes HIPPA training, covering donor and recipient confidentiality
3)Competency for all job duties performed (initial and annual)
4)Continuing education
b.Policy for personnel training and competency assessment
1)Includes trainer qualifications with a uniform staff training plan
c.Sufficient personnel with adequate education, experience and training to competently perform duties/services required while achieving the highest product quality
d.Sufficient staffing to ensure compliance with regulatory agencies
- Related SOPs/documents:
GP: 3Personnel Training, Competency and Proficiency Testing
3.Protocol Development and Review – Process for protocol development, validation, approval, implementation, review, revision and archiving
a.Established and maintained protocols/procedures describing all operational aspects
b.Procedures designed to prevent the risk of introduction, transmission or spread of communicable diseases through the use of HCT/Ps
c.Critical procedures are validated and/or verified prior to implementation
d.The Director reviews and approves all SOPs before implementation,and annually thereafter
1)Medical Director reviews and approves collection SOPs before implementation
e.Procedures are readily available to personnel in operational areas to which they relate, or in a nearby area if such availability is impractical
f.A defined improvement plan is in place to allow recognition, investigation and CAPA when deficiencies arise in existing processes
- Related SOPs/documents:
GP:2Standard Operating Procedures Preparation
QA:8Documenting Deviations, Addendums, Complaints and Accidents
QA:9Validation Procedures
4.Document Control --System for document control and records review relating to processing, storage, release and transportation
a.Any requirement for documentation requires that a record be created
b.Document Control system includes:
1)Current listing of all critical documents in the control system
- Standard Operating Procedures (SOPs)
- Worksheets – Process documents (i.e. Daily QC, apheresis collection, processing, etc.)
- Forms -- Consents, orders, tracking, distribution, notification, eligibility, and adverse events/reactions
- Labels used to identify and track products from collection to distribution
2)Unique alpha/numeric identifier for each document regulated within the system
3)A procedure for document approval, including the date and signature of approving individuals (SOPs) and the effective date of the document
4)A method to ensure that documents cannot undergo accidental or unauthorized modification
5)For SOPs, training documentation associated with initial activation and subsequent revisions
6)A method for document change control
- Includes change description, approving individuals signature (SOPs) and effective date
7)A method for obsolete document retraction to prevent unintended use
8)A method for record creation, assembly, storage, archival and retrieval
c.Q-Pulse
1)Document control activities are managed by Q-Pulse Quality Management software
d.General Document/Record Attributes
1)Accurate, indelible, and legible, written in blue or black ink
2)Identify the person performing the work and date completed
3)Documentation errors are corrected by a single horizontal line through the error, recording the correct entry with date/initials next to the correction
4)Records provide a complete history before product distribution
5)Records pertinent to HCT/P manufacture (labeling/packaging procedures and equipment logs, etc) are also maintained and organized under the record management system
6)The record management system allows prompt document identification, location and retrieval if maintained in more than one location
7)Records are maintainedelectronically, inoriginal hard copy, and/or photocopies
8)Equipment necessary to obtainlegible records (i.e. computers) are readily available
9)Electronic records are backed up daily
10)All records are maintained for 10 years after their creation, unless stated otherwise
11)A contracts list, with names and addresses, including responsibilities, is also maintained
- Related SOPs/documents:
GP:13Patient Chart Preparation and Review
CP:14Product Labeling
GP:2Standard Operating Procedures Preparation Policy
QA:2Quality Control Procedures, Cleaning and Maintenance
QA:12Worksheet, Form and Label Preparation
5.Written Agreements
a.The QA Program incorporates policies and procedures for the establishment and maintenance of written agreements with third parties whose services impact ...’s products
1)A third party facility must comply with applicable laws, regulations and standards equal to ...
2)The agreement will define the roles and responsibilities for critical tasks
3)... ensures compliance
a)Confirmed by vendor qualification and/or audits as needed
- Related SOPs/documents:
QA:11Vendor Qualification
6.Outcomes Analysis -- Process for documentation and review of product efficacy following administration
a.BMT program coordinator offices (…) provide engraftment data as it becomes available
1)QA Supervisor inputs data into Sigma Plot™ and graphs data based on a product type
a)All data is analyzed based on the product type mean ±2 standard deviations
b)Graphs consist of a minimum three months of data for tracking and trending purposes
2)If delayed engraftment is evident, outside standard deviation range, a process for cause analysis and CAPA is documented, if applicable
3)Data is reported to the Facility Director and respective BMT programs quarterly
b.Criteria for non-HPC product efficacy is determined and reviewed at regular intervals as needed
- Related SOPs/documents:
... QA Reports
7.Quality Audits–...conducts independent quality audits and indicator reviews to confirm compliance with regulatory, FACT or institutional requirements
a.Audit performed by staff with expertise in the process but not solely responsible for its performance
b.Results used to recognize problems, detect trends and improve processes
1)Reportedat leastquarterlyto the Lab Director
NOTE: Audit results which identify the potentialforintroduction, transmission, or spread of communicable diseasesor harm to the donor or recipientare discussed immediately when discovered
c.Deviationsare managed per SOP QA:8
d.CAPAcompleted, tracked and documented as needed
e.Documentation maintained and permanently archived
1)Audit results are used to illuminate problems, identify trends and implement improvement
f.Indicators and audits include the following:
1)Indicator Reviews (Frequency)
a)Unit number (Monthly): All unit numbers are accounted for
(1)Each product, upon receipt, is assigned a unique unitnumber which relates any component to its donor, the donor’s medical record, and all records describinghandling and final component disposition
b)Donor infectious diseasemarker–Monthly (ID marker test/timely completion):
(1)HPC(apheresis, BM, Cord Blood): 30 days before collection
(2)Therapeutic cells/DLI (apheresis or whole blood): 7 days of collection
c)Microbiology Testing (Monthly): Confirm no positive cultures observed
(1)Positive tests are investigated for root cause
d)Processing Logs (Monthly): Product related logs/worksheets (workload, sign-in, distribution,flow cytometry, etc.) are accurate, legible, complete and initialed by responsible tech
e)QC (Monthly): Review all QC logs and forms for completeness, accuracy and tech initials
(1)Also confirm aberrant results were investigated, corrected and re-validated as required by QA Manager or Director
f)Freezerworks (Monthly): Ensure product inventory software is correct and up to date with current patient chart information
g)Engraftment (quarterly): See 6 above
2)Audits
a)Internal Focus Audits(Frequency)
(1)QA Manager/Lab Director Discretion
(2)Based on identified trends and/or deviations
(3)Indicators, frequency and duration determined according to specific situational needs
(4)Initial duration will usually be one year.
b)Electronic documents not validated
(1)Infusion Orders- created on excel spreadsheet which performs automatic calculations
(a)Calculations manually completed by Stem Cell Technologist prior to product release
(b)These documents are also reviewed by the Facility Director and Technical Manager
(2)Summary Sheets- created on excel spreadsheet which performs automatic calculations
(a)All data input is based off of worksheets in which calculations have all been performed manually and checked by a secondary technologist.
(b)Values on this sheet are compared with those values on the worksheets
3)External Audits
a)CFT allows facility , protocol, document, QC, adverse reaction and deviation auditsfrom 3rdparties for whom ... provides services or their representativeauditors
b)FACT(Foundation for the Accreditation of Cellular Therapy)
(1)Tri-annual inspection, entire university BMT program involved
(2)Lab is responsible for specific standards
(3)FACT audit results are documented and reviewed by ... staff
(a)Corrective action is implemented (as applicable) and documented
(b)The corrective action report is archived
c)College of American Pathologists (CAP) Audits
(1)Pre-inspection -- Internal audit a few months prior to the scheduled CAP inspection
(2)CAP non-inspections year- Bi-annual internal audit to assess CAP compliance(continuing accreditation terms)
(3)CAP audit results are documented and reviewed by ... staff
(a)Corrective action is implemented (as applicable) and documented
(b)The corrective action report is archived
- Related SOPs/documents/systems:
Q-Pulse Quality Management Software
QA:2Quality Control Procedures, Cleaning and Maintenance
QA:8Documenting Deviations, Addendums, Complaints and Accidents
Quality Indicator Audit Summaries
... QA Reports
GP:13 Patient Chart Prep and Review
8.Products with Positive Microbial Culture Results
a.When positive culture results are received, the following are notified:
1)Recipient physician, collection facility, or other processing facility as applicable
a)Clinical staff follows up with the donor/recipient according to their protocols
2)...Facility Director, Technical Manager/Supervisor, Apheresis Supervisor, and QA
b.Notification is recorded on Notification of Pending Results to Physician form and placed in the patient’s chart
c.The product is relabeled and relocated to appropriate storage location per SOP
d.All necessary documents are changed
e.QA performs investigation and a deviation report is initiated if applicable
1)If no deviation, a staff note documenting investigation results will be placed in the patient’s chart
f.Product may be released by authorized personnel after release criteria are met
g.QA will report the incident to regulatory agencies if applicable
- Related SOPs/documents:
GP:26 Positive Sterility Culture Product Handling
QA:8Documenting Deviations, Addendums, Complaints and Accidents
9.Detecting and Reporting Errors, Accidents, Adverse Events and Complaints:
a.Deviations from SOP are investigated and documented, to include root cause analysis and CAPA
1)Planned deviations are pre-approved by the QA Manager and ... Director(BMT Medical Director notified as deemed necessary by Director)
b.Adverse reactions (donor or recipient)and subsequent CAare reviewed by ... and Medical Directors
1)Adverse reaction written evaluation is included in the patient file and available to the patient/donor’s physician
2)Where applicable, the adverse eventsare reported to appropriate local, state and federal regulatory agencies
a)When an adverse reaction is caused by a collection procedure or infused cell component, the written report generated by ...isforwarded to and maintained by the collection and/or transplant facilities, as requested
IMPORTANT:ANY adverse reaction involving communicable disease related to an HCT/P made available for distribution MUST be investigated and reported if:
- fatal
- life-threatening
- results in permanent body function impairment/permanent body structure damage; or
- necessitates medical/surgical intervention, including hospitalization
If a deviation causes an increased risk of contamination or communicable disease transmission of a collected product, documentation and follow-up is required
Follow FDA reporting guidelines outlined in 21 CFR 1271.350
c.Complaints are communicated to the Technical Manager, QA and Director immediately
1)Management will investigate the issue with all involved parties and document findings in Q-Pulse to facilitate CAPA and tracking
d.All deviations, adverse reactions and complaintsare presented in ...staff meeting as soon as possible for information and input
1)Additional CAPA may be defined and implemented as needed
e.QA will determine deviation or event reporting in BMT QA meetings as well as regulatory reporting
1)QA will be responsible for reporting with Director input as needed
f.Employee concerns about quality and safety may be communicated during staff meetings open discussion
1)Concerns and follow-up are recorded in the meeting minutes
2)Other methods in which staff can communicate their concerns which will then be discussed in the next staff meeting:
a)Q-Pulse
b)All management, to include QA, Technical Manager and Lab Director
g.Process Improvement
1)Anyone who sees improvement opportunities, whether in a process (SOP), form or worksheet input a Change Request (CR) into Q-Pulse on the applicable document Record
2)CRs are sent by Q-Pulse to the document owner and author for review
a)They decide whether the change is high impact, warranting immediate revision, or can wait until the next annual review
b)CRs will be discussed with staff
c)Reasons for not implementing a CR will be reviewed with the submitter
- Related SOPs/documents:
QA:8Documenting Deviations, Addendums, Complaints and Accidents
GP:5Progenitor Cell Infusion Reaction Workup
CC:7Management of Adverse Reactions in HPC Donors
QA:12Form, Label and Worksheet Preparation
GP:2Standard Operating Procedures Preparation Policy
10.Product Tracking --The QA Program includes product tracking from donor to recipient/final distribution and visa versa
a.Each HCT/P is assigned and labeled with a unique identification
1)The unique IDfacilitates HCT/P tracking from the donor to the recipient and back
2)All HCT/P records contain the unique ID
3)The unique ID does not include name, social security number or medical record number (MRN)
b.Another unique ID may be adopted by another manufacturing facility
1)The new ID will be documented in the patient record to relate to the old ID
c.SOP dictates to recordand document the unique ID code, HCT/P type and disposition when distributed to a consignee to enable tracking
d.Consignee is informed in writing of these requirements and the product distributiontracking system
- Related SOPs/documents:
CP:14Product Labeling
GP:4Issue, Release and Return of Products Intended for Transplant
GP:7Receipt and Handling of HPCProducts
GP:8HPC/T Transfer and Transport
GP:19Product Release for Research or Disposal
11.Continuous operations when electronic systems are inoperable
a.Immediately notify the appropriate electronic system personnel and proceed as listed below until the system is fixed
b.Electronic systems used in daily ... activities are backed during operational down times as follows:
1)Freezerworks – Product Inventory Software
a)Hard inventory location copies and disposition in each patient file
b)QA Supervisorprints a list of available freezer space every week
c)All electronic files are automatically backed up daily
2)REES – Environmental Monitoring System