Sourcing Human Blood-Derived Raw Material: Optimization, Qualification and Control

 

 

 

Pete van der Wal; Anna Stock

HemaCare Corporation

(877) 397-3087  •  astock@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 material for cell therapy, tissue-engineered, and ex vivo gene therapy products. Quality of this cellular raw material is a major determinant of final product characteristics, but is complicated by the inherent heterogeneity and inter-individual variability of living biologics. Inconsistent collection procedures amplify this variability, adversely affecting the manufacturing process from the outset. Controlling and qualifying the cell collection step is essential to minimizing operational variability, and greatly increases the likelihood of success in manufacturing. HemaCare’s core competency is apheresis collection, and, building on 34 years of experience, has addressed this need for optimized cell collection with a program for controlling and qualifying its apheresis procedures and collection sites, to supply human-derived blood components for development and qualification of novel cell and gene therapies, assays, and medical devices. HemaCare’s apheresis program includes comprehensive staff qualification and training, documentation that supports its cGMP environment and programs to monitor effectiveness of equipment and procedures in accordance with an established quality system. Donor recruitment, screening and IRB-approved consents follow the requirements of Good Tissue Practices (GTPs). From 2006-2010, 55,262 apheresis procedures were performed, including collection of patient and normal-donor peripheral blood mononuclear cells, mobilized peripheral blood progenitor cells, and plateletpheresis products, to support clinical studies spanning Phase I-Phase III, preclinical research, and, for the first time, commercial cell therapy applications. This reflects the evolution of cellular therapies.

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
  • Inconsistent collection techniques amplify inter-individual variability, adversely affecting manufacturing processes
• Quality systems standardize and control operations
• Training and experience are critical

Apheresis Expertise in a Quality Framework

• Optimize cell collection by controlling and qualifying the apheresis process, based on cGMP and cGTP principles
  • Development and maintenance of technical procedures
  • Comprehensive staff training and qualification
  • Monitoring apheresis equipment in accordance with an established quality program
  • Internal and external inspections
  • Monitoring quality indicators for process improvement
  • Qualification of donor/subject under IRB approval and in compliance with cGTPs

HemaCare Apheresis Products

• Customized apheresis products
  • Specific donor characteristics, cellular composition, collection/handling parameters
• Mononuclear cell (MNC) collection
• Platelet and plasma collection
• Support R&D, clinical trials and licensed products, transfusion, device validation, assay development

Controlled Procedures and Documentation

• All activities governed by written procedures
  • Developed using standardized process, reviewed and approved by subject matter experts and QA
  • Procedures validated prior to release
  • Proposed variances reviewed through exception management
• Incorporate research protocols, regulations, manufacturer’s input, IRB requirements
• Master Control - validated, computerized document management system

Staff Qualification and Training

• Recruitment, training, and proficiency are critical to a consistent product output
• Job descriptions outline qualifications, educational requirements, work experience, capacity to provide compassionate care
• Training program covers procedures, equipment, “soft skills”

• Training includes competency assessment prior to release
• Staff performance is monitored through quality indicators

 

Equipment Management

• Apheresis platform - COBE Spectra Apheresis System
• Equipment management system ensures apheresis equipment operates efficiently and within specifications
• Equipment validation - IQ, OQ, PQ
• Equipment monitoring logs and performance tracking
• Preventive maintenance program to assure optimal performance
  • When necessary, equipment is removed from service, repaired, and validated prior to return to service

Deviation Management

• Deviation: A variation from SOPs, cGMP, cGTP standards or specifications; may affect product quality or donor safety
• Capturing deviations
  • All staff report deviations when noted
  • Immediate actions are performed
• Corrective and Preventive Action (CAPA)
  • Root cause analysis
  • Develop and carry out corrective/preventive actions
• Track/trend deviations for process improvement
• Managing and preventing deviations maintains product consistency and reduces final product variability

Internal Quality Indicators

• Deviation management summary reports
• Equipment performance monitoring and tracking
• Staff competency assessment
• Product characteristics, statistical evaluation
  • Nucleated cell (WBC) content and subpopulations
  • Mononuclear cell % and total content
  • Immunophenotype, if needed
  • Volume, hematocrit, other

Product Characteristics, Quality Indicators

External Quality Indicators

• Feedback from customers and patients is critical

External Quality Indicators

• High level of satisfaction led to request for expanded services at additional sites

Donors – the Critical Source

• All donors/subjects are qualified per cGTPs and protocol requirements, with IRB-approved informed consent
• Pedigreed donor database
  • Further minimizes variability, facilitates recruitment of donors with specific characteristics required by investigator
• Age, gender, ethnicity, height/weight
• HLA type, other specific laboratory test results
• Medical history – vaccinations, diet, social habits, family history
• Repeat donors

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 qualification and training, equipment management, and monitoring of quality indicators reduce this variability
• Availability of repeat donors from a pedigree database enhance the quality and value of this critical, living biological material