Cell line development: Reducing timelines and increasing titres by identification of host cell lines with improved characteristics. To develop a mammalian expression platform which rapidly leads to efficient, robust and high quality biomanufacturing processes

1. FUJIFILM Diosynth Biotechnologies Introduces:
For more information, visit: www.FujifilmDiosynth.com/Apollo

2. Who is Fujifilm Diosynth Biotechnologies?
Fujifilm Diosynth Biotechnologies is a leading global Biologics Contract Development and Manufacturing Organization
We have locations in Billingham, UK and Research Triangle Park, NC, USA.
We have industry leading experience with Over 230 Development and Manufacturing Projects.
We are licensed to manufacture five (5) commercial products.

3. Regulatory
Approval
Launch
Phase III
Phase I
Phase II
Preclinical
Gene Expression &
Strain / Cell Line Development
Process Invention
Pre-clinical
Manufacture
Process Development & Optimization Analytical Development Formulation Development (DS, DP) cGMP Manufacture
Process
Characterization
Process Validation
cGMP Manufacture
cGMP Stability (DP, DS)
Commercial
Production
Post-approval
Activities
A long-term Partner through Product Lifecycle

4. Full Service Cell Culture Offering
•
Proprietary host cell line
•
Proprietary vector
•
Media/Feed Platform
•
CLD Process
Process and
Analytical
platform
cGMP
Manufacturing
platform
•
mAb DSP Platform
•
Platform mAb analytics
•
cGMP cell banking
•
160-2000L SS cGMP plant (US)
•
200-2000L SU cGMP plant (US & UK)

5. What is the Apollo™ platform?
•
Apollo™ is a mammalian expression platform developed by FUJIFILM Diosynth Biotechnologies’ scientists.
•Apollo™ was created with manufacturability as an end- goal.
•Apollo™ will deliver a high quality recombinant cell line to take your biopharmaceutical from pre-clinical through to commercial production.
Apollo™, a cell line for life.

6. Components of the Apollo™ mammalian expression system

7. Summary of FDB Mammalian Cell Line Development and Upstream Process Development R & D Services
Vector design and construction
Transfection
Expansion and selection
Cloning
Expansion and selection
RCB
Cell line stability study
Process establishment
Process demonstration
Process development / optimization
cGMP MCB / WCB
cGMP manufacturing
Process characterization
Cell Line Development
Process Development

8. Apollo™ Components: Host Cell Line
Adapted to CD media
Host cell line
CHO DG44 derived
Fully characterized cGMP cell bank of host cell line with maximum traceability
Developed using a directed evolution approach
Selected for superior growth characteristics and expression capability
Adapted to chemically defined medium and suspension culture

9. Apollo™ Components: Vector
Adapted to CD media
DHFR based selection system
High productivities achieved without the need for amplification
Vector
Double gene vector for mAbs
Proprietary leader sequence developed for efficient secretion
Codon optimization utilised

10. Adapted to CD media
Animal component-free media and reagents throughout cell line development
Up to 3 g/L typically seen pre-optimization
Pooled transfection and / or clonal cell line development
State-of-the-art screening strategies
Process
Robust cloning strategy: high probability of monoclonality
Apollo™ Components: Process

11. •
From preclinical to market
•
Regulatory friendly
•
Rapid Clinical material
•
Early representative material
•Attractive terms
What are the Benefits?
Speed
Business friendly

12. 2) First screening & cloning step: ClonePix™ 2
1) Transfection & selection
3) Expansion, first 96-well plate screen & first shaken, fed-batch multi- well plate screen
4) Second cloning step: ACF limiting dilution cloning
Our Cell Line Development Approach
6) ambr15™ Screen
7) Research cell bank
5) Expansion, second 96- well plate screen & second shaken, fed-batch multi-well plate screen
Transfection to RCB of clonal cell line = ~25 weeks
Possible program break point
Generation of material from transfectant pools
Stability study, Process Development, etc.

13. Apollo™ Timeline
Time (weeks)
1 . . . 5 . . . .10 . . . . 15 . . . . 20 . . . . 25
Vector construction
Cell
line
Representative material (transfectant pools)
Pre-clonal cell line
for DSP &
early supply
RCB of
clonal
cell line

14. Summary: The Apollo™ System
Key aspects of the expression system are:
•
DHFR based selection system
−
High productivities achieved without the need for amplification
•
DG44 derived host cell line
−
Adapted to chemically-defined medium and suspension culture
−
Selected for superior growth characteristics and expression capability
−
Fully characterized cGMP cell bank of host cell line with maximum traceability
•
Optimised cell line development process
−
Animal component-free media and reagents for the complete cell line development process
−
High probability of monoclonality (experimental and statistical evidence to support approach)
−
Inclusion of state-of-the-art screening technologies, allowing improved prediction of the ‘best’ cell lines to progress: ClonePix™; fed-batch, shaken multi-well plate system; Ambr15™
•
Product concentrations up to 3 g/L typically seen pre-optimisation
−
FUJIFILM process development strategy available for further optimization

15. www.fujifilmdiosynth.com/Apollo