Optimizing Apheresis Cellular Collections
Optimizing Apheresis Cellular Collections
Gaytha McPherson, MT(ASCP), CLS
HemaCare Corporation
(877) 397-3087 | bioresearchproducts@hemacare.com
Scott R. Burger, MD
Advanced Cell & Gene Therapy, LLC
(919) 969-1103 | celltherapy@ac-gt.com
Abstract
Human cells and tissue are critical raw materials for cell therapy and tissue-engineered products, as well as ex vivo gene therapy products. Quality of this living cellular raw material is a major determinant of final product characteristics, but inter-individual variability and biological heterogeneity are complicating factors. Controlled, qualified cell collection minimizes operational sources of variability, increasing likelihood of successful manufacturing. HemaCare, a long-standing supplier of human-derived blood components for novel biologic therapies and assays, medical devices, and clinical applications, established a program for controlling and qualifying its apheresis procedures and collection sites. This includes comprehensive staff training and qualification, documentation supporting cGMP operations, equipment and procedure validation, and monitoring in accordance with a rigorous quality system. Donor recruitment, screening and IRB-approved consents follow cGTP requirements. The quality program tracks and investigates deviations from process, complaints, and error rates in specific categories, representing donor screening and testing, collection, product preparation, testing, labeling, distribution, and cGMP/cGTP systems. As part of continuous process improvement, in 2011 HemaCare validated or re-validated 14 apheresis instruments for mononuclear cell (MNC) collections at 3 collection sites, using cGMP validation standards established for platelet collection, and validated a new automated cell analyzer, the Horiba Pentra XL80. HemaCare performed 69,658 cellular apheresis collection procedures in the last five years, including collection of patient and normal-donor peripheral blood MNCs, G-CSF-mobilized peripheral blood progenitor cells, and plateletpheresis products, supporting commercial cell therapy and clinical trials, preclinical research, and validation studies. Unmobilized apheresis products were appropriately MNC-rich with an overall average of 85.2% MNC ± 6.6% (mean ± 1 SD). Rigorous quality systems enable controlled, consistent cell collection, a critical factor for development and commercialization of novel cell-based products and technology.
Human Cells: Standardizing Living Biological Raw Material Through Quality Processes
- Human blood-derived cells are critical raw material for cell therapy, tissue-engineered products, and ex vivo gene therapy products
- Quality and consistency of cellular raw material is a major determinant of final product characteristics
- Controlling cell collection minimizes variability and increases likelihood of success in research and manufacturing
- Training and experience are critical
- Quality Systems standardize and control operations
HemaCare Expertise in Apheresis and Service
- Therapeutic apheresis
- Mobilized stem cell
- Collection
- Apheresis platelets
- Collection and processing for transfusion and research
- PBMC collection
- Assay development
- Device validation
- Clinical trials
- Research
- Cell-derived cancer vaccine therapy
- Licensing and accreditation
- State of California
- Biologics Production
- Clinical Lab
- Other states: Connecticut, New York, New Jersey
- FDA registered
- AABB accreditation
- Blood bank services
- Cellular product services
- CLIA
- FACT (in support of customer hospital stem cell programs)
- State of California
Apheresis Expertise in a Quality Framework
- Optimize cell collection by controlling and qualifying the apheresis processes based on cGMP and cGTP requirements
- Qualification of donors
- Qualification of vendors, equipment, supplies and sites
- Monitoring equipment, supplies and environment
- Development and maintenance of procedures
- Comprehensive staff training and qualification
- Documentation and records management
- Management of exceptions and deviations
- Monitoring quality indicators for process improvement
- Internal and external inspections
Cellular Apheresis Collection Procedures
Donors – The Critical Source
- All donors are qualified per regulations and protocol requirements, with IRB-approved informed consent
- HemaCare apheresis donor population
Repeat Platelet Donations |
Percent of HemaCare |
5 or more times |
85% |
20 – 24 times |
> 40% |
- Pedigreed donor database
- Qualification and testing performed with each donation
- Facilitates recruitment of donors with specific characteristics required by investigator
- Age, gender, height/weight, ethnicity
- Medical history – vaccinations, diet, social habits, family history
- HLA type, other specific laboratory test results
- Repeat donors further minimize variability
Equipment Management
- Equipment management processes ensure apheresis equipment operates efficiently and within process specifications throughout equipment lifecycle
- Equipment selection
- Equipment validation – IQ, OQ, PQ
- Preventive maintenance
- Corrective maintenance
- Equipment QC and performance tracking
- Apheresis platforms
- TRIMA Accel® Automated Collection System – Platelets
- COBE® Spectra Apheresis System - PBMCs, Stem Cells, TA
Controlled Procedures and Documentation
- All activities governed by written procedures and policies
- Developed using a standardized process
- Reviewed and approved by subject matter experts and QA
- Validated prior to release
- Incorporate regulations, manufacturer's requirements, research protocols and IRB requirements
- Controlled: Computerized document management system
- Proposed variances approved through Exception Management
- Documentation and record retention requirements met
- Traceability of each product collected
Staff Qualification and Training
- Recruitment, training, and proficiency are critical to a consistent product output
- Job descriptions outline licensure, qualifications, educational requirements, work experience
- Training program covers standardized procedures and equipment, and "soft skills"
- Training includes 6 months with preceptor and multiple competency assessments prior to release
- Quality indicators monitor staff performance
SPECTRA: Separation of Blood Components
MNC Collection
Quality Indicators
- Tracking and trending
- Donor reactions, deviations, exceptions, suppliers, risks, equipment performance, etc…
- Product and donor QC statistics
- Product
- Nucleated cell (WBC) content and subpopulations
- Mononuclear cell %
- HCT, product volume, etc…
- Donor
- Pre-procedure CBC
- WBC – 5 part differential
- Product
- Internal and external audits
Quality Indicators: Apheresis Product Quality: Mononuclear Cells
- Non-mobilized apheresis collections, n = 174
- 93.8% of products ≥ 75% mononuclear cells
- MNC-rich products overall, but occasional outliers for QA investigation, and process monitoring/optimization
Quality Indicators: MNC Product Quality: Hematocrit
- Hematocrit 1.8% ± 0.8% (mean ± 1 SD), range 0.0%-6.4%
- 91.3% of products ≤ 2.5% hematocrit
Quality Indicators: Repeat-Donor Products: % Mononuclear Cells
- 21 repeat donors, each representing 3-5 products
- Little or no relationship between % MNC of donor peripheral blood and apheresis product
- However, % MNC of apheresis products from an individual donor appears more uniform and predictable compared to apheresis products overall
- CV of % MNC averaged 3.5% for products from an individual donor
- CV of % MNC averaged 7.7% for all products
External Quality Indicators
Dendreon Supplier Scorecard
External Quality Indicators
Summary
- Collecting blood-based cellular products in a manner that minimizes variability brings a higher degree of reproducibility to the research project or manufacturing effort
- Quality-based controls such as standardized SOPs, staff training and competency assessments, equipment management, and monitoring of quality indicators reduce this variability
- Availability of repeat donors from a pedigreed donor base enhances the quality and value of this critical, living biological material
