COGS by Design: a systems approach to achieving commercially viable cellular therapy products. Tim Oldham 27 May 2016 ISCT 16 - Singapore

Transcription

1 COGS by Design: a systems approach to achieving commercially viable cellular therapy products Tim Oldham 27 May 2016 ISCT 16 - Singapore

2 Summary Identifying the total needle-to-needle cost of therapy to healthcare systems against its healthcare must be the starting point for intelligent product and process development (COGS by design) Understanding cost drivers, including the costs of quality, early in process development maximizes opportunities to achieve viable product costs Multiple process design and deployment choices are required to optimise COGS and the choices are different for autologous and allogeneic therapy 21 July 2016 Page 2

3 Target product profile (and hence COGS target and manufacturing strategy) is influenced by multiple stakeholders other than the scientist Regulator: how is product reproducibility, consistency and safety assured? Commercial access: how do I maximize patients who can be treated (and donations that can be accepted into production)? What manufacturing strategy? Payor: is the product cost effective relative to standard of care? Are the associated procedures funded? Logistics: what is incoming and outgoing product shelf-life? Is there are cryo-protected hold step? User: does this interrupt my current treatment/referral flows and revenue? Page 3

4 COGS improvement opportunity summary $ per patient Clinical site cost DISGUISED CLIENT EXAMPLE Transplant Apheresis Manual process at scale Logistics Vector Apheresis site management Next Gen processing Alternate CD34+ selection Sponsor cost QC assay cost QC assay reduction innovation Future Gen processing Eliminate 2nd apheresis Target process Processing Manual process at scale Apheresis site management Next Gen processing Alternate cell selection QC assay cost reduction QC assay innovation Eliminate 2nd apheresis Target process Source: Disguised client example Page 4

5 Sponsor s COGS drivers: multiple levers must be pulled Manufacturing costs: manual gene modified process at scale 100% = $50-90k QC/release assays 25% LVV 19% Achieving a notional target COGS <$30k requires 65% reduction Labour 20% Facilities 8% Materials and reagents 28% Release testing, reagents and consumables, and facility costs contribute approximately equally to total product costs Cost reduction solutions must address all three areas Source: Disguised client example Page 5

6 Apheresis variability drives manufacturing cost complexity Collection algorithms Manufacturable product range (taking into account process losses) Early indicators of quality risks Key attributes T-cells: collection efficiency then composition CD34+: collection efficiency then composition Monocytes for DC therapy: composition then collection efficiency Site monitoring and benchmarking Threshold to commence collection % Gran Page 6 Site remediation? Operator remediation? Max contamination for manufacturability EU-A US-B US-C APAC-D Site

7 Stage Start early: avoid locking in costly processes Foldexpansion Lab scale (static) Optimisation 1 Target Density (rel value) Volume (L) Density (rel value) DISGUISED CLIENT EXAMPLE Volume (L) Density (rel value) Volume (L) A B C D Final density Doses Cost/dose (reagents) $176k $22k $3k Drivers Stage D = 92% One growth factor = 57% Stage C = 72% All stages ~25% Stage D feasibility Stirred culture Page 7 Halve growth factor PD goals Perfusion culture Recombinant growth factor

8 Overarching goals for commercial manufacturing Process development and tech transfer goals Technology transfer approach (6-12m) Quality Maximize product AND process consistency, reliability and reproducibility Scalability Minimize process changes at each level of scale-up/out Maximize capital efficiency (modularity, staged investment, multi-use facilities and technologies) Sustainability Ability to drive continuous improvement Anticipate COMPARABILITY COGS Minimize COGS (total cost per patient across supply chain) Page 8

9 Autologous production for the future requires a systems approach Cost/10 6 cells infused Collection cost Processing cost Capital cost Operations cost Yield QC cost Process equipment Facility Process optimisation Process automation Facility optimisation Supply chain optimisation Information optimisation Delivery cost Enablement Page 9

10 Key design choices/philosophy Collection apheresis/biopsy Collection - cryopreservation Local Local Central Central Autologous Allogeneic Process automation Unit operations Entire process Process automation Off-the-shelf Bespoke Process closure Functionally closed Completely closed Equipment strategy Re-usable Disposable QC strategy Off-line In-line Facility scale Distributed Centralised Facility use Product specific Multi-product Capital investment One time Staged Page 10

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