Cellca Technology Platform

Transcription

1 Cellca Technology Platform Custom Cell Line & Process Development April 2018

2 Overview: Cellca Technology Platform Cellca CMO/Client Cell Line Development Process Development Process Transfer GMP Production Downstream Processing Fill & Finish Host cell line Expression Vector Media System Upstream Process Design Host Cell Line: CHO DG44 growth in suspension, 18 h doubling time, long term stability Expression Vector: DHFR selection system, metabolic Selection, low DHFR expression, S/MAR elements, optimal signal peptide Media System: Optimized, chemically defined, free of animal components, proteins & peptones, high cell densities, viabilities & productivity Upstream Process Design: robust, easy to scale, proven performance in various bioreactor systems 2

3 Host Cell Line Features: CHO DG44 (DHFR-deficient) Suspension growth Chemically-defined medium 18 h doubling time Long-term stability Host cell line history report 3

4 Expression Vector Features: DHFR selection system Metabolic selection (HT-) MTX-free Monomeric and dimeric products Low DHFR levels: stringent selection S/MARs: enhanced and stable expression Signal peptides: enhanced secretion Freedom-to-operate 4

5 Media System Features: Optimized for CHO DG44 Completely chemically defined No animal components, proteins, peptones Commercially available Stock Culture Medium Cultivation and adaptation Production Medium Feed Medium A Feed Medium B Production in fed-batch culture 5

6 Fed-Batch Process Features Standard Fed-batch process: defined media & feeding No media and process optimization Good product yields and quality Reproducible and robust Low lactate levels Easy scalable ambr 15/250 5 L bioreactor 50/200/1000/2000 L bioreactor 6

7 Our Timelines: DNA to RCB in 4 Months Vector Cloning Transfection and Pool Generation Single Cell Cloning Clone Evaluation RCB Preparation From DNA to RCB in 4 From DNA to RCB within 4 months Slots available without reservation No need for media and process development 7

8 Viable cell concentration [10 5 cells/ml] Viability [%] Product Concentration [g/l] Scalability Time [days] VCC Univessel 5 L VCC STR 200 L VCC STR 2000 L Viability Univessel 5 L Viability STR 200 L Viability STR 2000 L Product Univessel 5 L Product STR 200 L Product STR 2000 L

9 concentration [ g/l ] Scalability and Robustness L stirred bioreactor L stirred bioreactor Time [ d ] 50 L wavemixed bioreactor Glucose - 50 L stirred bioreactor Glucose L stirred bioreactor Glucose - 50 L wave-mixed bioreactor Glucose L wave-mixed bioreactor Lactate - 50 L stirred bioreactor Lactate L stirred bioreactor Lactate - 50 L wave-mixed bioreactor Lactate L wave-mixed bioreactor 200 L wavemixed bioreactor 9

10 25 ml shake flask 5 L bioreactor 200 L bioreactor 1000 L bioreactor G1/G0 ratio G2/G0 ratio Fucosylation [%] Product Quality and Scalability G1/G0 ratio G2/G0 ratio Fucosylated forms [%] Product titer [g/l] 10

11 Performance - Quality Targeted modification of quality attributes (e.g. glycosylation pattern) Application for biosimilar projects Scalability of modifications 11

12 Performance Efficient cost reduction by achieving steadily productivities of 3g/L or more Cost reduced by 50% by omitting media and process optimization Cost of Goods /g 1000 Clone distribution Cellca*

13 Track Record (April 2018) Pre-clinic & Phase 1 2 g/l 3 g/l 4 g/l 5 g/l 6 g/l Phase Phase Monoclonal antibodies (IgG1, IgG4, IgG2) Bispecific antibodies Fc-fusion proteins Fab-related products Biosimilars 13

14 Project Management Detailed Discussions F2F, TCs Final proposal Kick Off PROPOSAL: Direct service and support by Product Management Team: Adelheid Burkhardt Dr. Lucia Rieger Brian Wendelburg Lisa Blaschke Birgit Schumacher (Head of Team) Service and License Agreement Data Packages Regular TCs Scope changes possible PROJECT: Committed project team & close contact with Customer Order Manager: Alexander Pietschmann Sharon Phillips Martina Frik Heike Mayer (Head of Team) Final report 14

15 Benefits of Cellca Technology Platform SPEED From DNA to high-titre RCB in 4 months. Save up to 3 months by omitting the need for scalability studies. SCALABILITY Processes can be easily transferred and scaled-up to a range of bioreactors up to 2000L. PERFORMANCE 95 % of our developed cell lines deliver protein titers exceeding 3 g/l in a day standard fed-batch process. TRACK RECORD More than 70 successfully completed projects using the Cellca CHO Expression Platform. CUSTOMER FOCUS Committed project teams and dedicated client manager s make it their purpose to deliver service excellence and meet our clients requirements. 15