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