New technologies in cell therapy
manufacturing
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Dominic Wall PhD FFSc (RCPA)
Chief Scientific Officer
Cell Therapies Pty Ltd
Operations Director- Pathology & CBCT
Peter MacCallum Cancer Centre
Cell Therapies
• A commercial therapeutics manufacturer
• Majority owned/controlled by a cancer centre
• 4 x Manufacturing GMP licences
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149827 Stem Cells -2001
162398 Orthogen Australia- chondrocytes- 2003
MI-2009-LI-05411-3 Mesoblast- Mesenchymal
Precursor Cells- July 2010
Immunotherapy licence – Prima Biomed-February
2012
• Trial CMO and other commercial & academic
activity
• Consulting, trial and product approvals
• Product and process development
• Affiliates in Japan and Malaysia
• 14 TGA OMQ audits over 11 years
Product range
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MACI
MSC
◦ Allo MCB derived doses
◦ Auto marrow derived & purified and cultured
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Pancreatic Islets
ADME and cell tracking
Automation, robotics, material procurement
Immunotherapies
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CTL with artificial antigens
T with artificial receptor to TA
DC with lysate
DC with peptide
DC with protein/carbohydrate
Cell vaccines- tumour cell line MCBs
Inherent challenges for patient directed
products
Medicinals
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No collections/donors
Large lots
high throughput
term sterile
control of starting materiel
complex processes
Stable complex protocol
unknown recipient
Cells and Tissue
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Donors and collections
single product lots, high value batches
low throughput
Partial closed system, no term sterile
Traditionally labour intensive
limited control of starting materiel
Evolving research based protocols,
Known recipients
Why and when to automate?
• To reduce ultimate COGS?
– Minimise use of controlled environments
– Reduce high cost materials & reagents
– Reduce product release failures
– Minimise FTE investment
• To avoid fossilizing an inefficient process from early
product development history?
• To avoid repeating pre-clinicals/clinical studies due to
comparability issues?
• Based upon materials suitable for multiple markets and
for the product lifetime?
• To reduce inherent process variability?
Allo vs Auto
• How can we access the evident benefits of evidently
reduced Facility COGs with larger batches?
– 1,000 doses/yr = 49% of COGs
– 100,000 doses/yr = 15% of COGs 1
• How can we reduce cost of materials?
• x doses/year = x aseptic steps/day?
• How can be reduce product variability so that it can be
applied at multiple sites?
• How can we support the process to have a drug product
correctly formulated at the treatment site?
• Can automation address support directed products
1 Developing scalable bioproduction processes: Integrating
upstream and downstream processing and controlling cost of
goods; Rowley JA Cell Therapy Bioprocessing 2011
Quality by release certificate
or by PAT?
Day 6 (Pre)
Day 6 (Post)
Final Fill (Aliquoting)
Final Product
Mycoplasma:Local Regulatory Requirements (EMA, FDA or TGA): not
detected
FACS: Total Viable DC: ≥
Viability: ≥ 70%
%DC : Information only
Appearance:
Volume:
Container Label:
FACS:
Total Viable DC x%
Phenotype DC : Information only
% Non DC: in CD45+ cells: FIO
Sterility: As per Local Regulatory Requirements (EMA, FDA or TGA): No
bacterial or fungal contamination detected
Endotoxin: As per Local Regulatory Requirements (EMA, FDA or TGA)
Potency: Bioassay : Information only
Should you still be doing this by Phase 3?
Centre for Blood Cell Therapies
Prof Miles Prince
Prof David Ritchie
Dr Dominic Wall
Dr Kirsten Herbert
Dr Simon Harrison
Maureen Loudovaris
Peter Gambell
Alannah Evans
Kerrie Stokes
Elise Butler
Tanya Bianchi-Rossi
Lucy Kravets
Wendy Chung
Ayse Mouminoglu
Luiza Mints-Kotowska
Gianna O‘Donnell
Nicole McCarthy
Thu Lam
Dimitrios Tsavios
Javier Haurat
Tammy Esmaili
Martin Bleasdale
Jyoti Arora
Carmen Chong
Gabby Workman
Valerie Costa
SiChong Zhou
Ray Wood