Manufacturing Resources

• Quality flowchart and checklist, European Medicines Agency (EMA)   
• Gene therapy manufacturing process map, Biophorum (CGT)
• Cell therapy manufacturing process map, Biophorum (CGT)
  • contains detailed process maps for multiple types of cell therapies.  
• Manufacturing and Preparation Toolkit, The Advanced Therapy Treatment Centres (ATTC)
  • case studies coming soon
• Manufacturing process development of ATMPs within a regulatory framework for EU clinical trial & marketing authorisation applications 
• Manufacturing genetically modified T cells for clinical trials  
  • regulatory part is USA (FDA) perspective 
  • contains: 1) flow chart for processes involved in manufacturing genetically modified T cells using the transposon, retroviral and lentiviral methods. 2) table for release criteria: manufacturing procedure must be validated to meet pre-established specifications (release criteria) to provide evidence for cell identity, potency, purity and safety. 
• Cell-based therapy technology classifications and translational challenges 
• Concise Review: Guidance in Developing Commercializable Autologous/Patient-Specific Cell Therapy Manufacturing 
  • provides guidance to small academic or biotech researchers in developing commercialisable autologous and patient-specific manufacturing strategies from the perspective of process development
• Global Manufacturing of CAR T Cell Therapy  
• Commercial Scale Manufacturing of Allogeneic Cell Therapy
• Analytical considerations for cellular therapy manufacturing

Manufacturing Authorisation

This section is in development.

Good Manufacturing Practice

• GMP requirements and Q&A, European Medicines Agency (EMA)
• Preparing for commercial GMP manufacture; areas for consideration, Cell and Gene Therapy Catapult (CGT Catapult)
• Viral Vectors: what are the solutions to current supply challenges, Cell and Gene Therapy Catapult (CGT Catapult)
  • see page 12 for a summary of analytics used for viral vectors
• GMP checklist for ATMP manufacture, ATMP Sweden
• Pluripotent stem cell differentiation to Megakaryocytes process flow chart and process analysis 
• Review: A guide to manufacturing CAR T cell therapies 
• Clinical manufacturing of CAR T cells: foundation of a promising therapy 
• GMP CAR-T cell production
  • review paper on manufacturing infrastructure, the regulatory environment, practical aspects of production, and the costs involved. Contain a flow chart for CART-T manufacturing process, a comparison table for vectors used for transfection.
  • regulatory part is USA perspective 

Selection of GMP cell line

Process validation

• Cell and gene therapy validation challenges, Biophorum Cell and Gene Therapy (CGT)

Generation of master and working cell banks

• Framework for master cell bank (MCB) testing and release, Biophorum Cell and Gene Therapy (CGT)  
• Development and production of good manufacturing practice grade human embryonic stem cell lines as source material for clinical application 
• Quality control guidelines for clinical-grade human induced pluripotent stem cell lines
• Special issue in pluripotent stem cell banking

Development of Standard Operating Procedures (SOPs)

GMP Training – Validation and Execution

CMC (Chemistry, Manufacturing, and Controls)

• Project A-Gene,  Alliance for Regenerative Medicine (ARM)
• Manufacturing genetically modified T cells for clinical trials  
• Validation overview of bio-analytical methods
  • Overview on the various regulatory considerations required when validating an assay procedure in compliance with GLP (Good Laboratory Practice) and cGMP (current Good Manufacturing Practice). Also, few bio-analytical methods, PCR, enzyme-linked immunospot (ELISPOT) assay, Microarrays and Limulus Amebocyte Lysate (LAL) test, have been selected for discussion. 

Release Testing

• The role of a Qualified Person (QP) within ATMPs, Advanced Therapies Treatment Centres (ATTC)  
• Manufacturing genetically modified T cells for clinical trials
  • manufacturing procedure must be validated to meet pre-established specifications (release criteria) to provide evidence for cell identity, potency, purity and safety 
• Clinical manufacturing of CAR T cells: foundation of a promising therapy 

European Pharmacopeia

• European Pharmacopoeia, The European Directorate for the Quality of Medicines & HealthCare (EDQM)
  • provides a legal and scientific basis for quality control during the development, production and marketing processes
• Knowledge database, The European Directorate for the Quality of Medicines & HealthCare (EDQM)
  • provides information on a given substance or general method of analysis 
• Collection of Guides to quality and safety for tissues, cells, and organ transplantation, The European Directorate for the Quality of Medicines & HealthCare (EDQM)
• Good Practice Guidelines for blood establishments, The European Directorate for the Quality of Medicines & HealthCare (EDQM)
  • see other related topics in blood transfusion section such as: Blood guide, Blood Proficiency Testing Scheme (B-PTS), Quality Management System (QMS)

Investigational Medicinal Products Dossier

This section is in development.

Capability

This section is in development.

Scalability

This section is in development.

Packaging and Labeling

• Supply chain challenges for manufacturing scale up, Advanced Therapies Treatment Centres (ATTC)
• Information on medicinal products, European Patients’ Academy on Therapeutic Innovation (EUPATI) 
  • four required types of information on labels: 
    • Labelling on package (immediate and carton) 
    • Summary of Product Characteristics (SmPC) directed towards healthcare professionals 
    • Package Leaflet (PL) directed towards the patient 
    • European Public Assessment Report (EPAR)