The document discusses essential considerations for the successful development and commercialization of life science products, emphasizing business, cell line, process development, regulatory, and technology factors. It outlines the importance of speed to market, process efficiency, and patient safety, while recommending strategies for effective decision-making throughout the drug development process. Ultimately, it highlights that a focus on product quality and scalability is crucial for achieving success in clinical development.

1. Guillaume Plane
December 2017
Breaking Down Roadblocks to Commercial Success

2. 2 A Molecule's Journey Webinar | December 5, 2017
The life science business of
Merck KGaA, Darmstadt, Germany
operates as MilliporeSigma
in the U.S. and Canada.

3. A long Journey from decisions to success
Key decisions Expected success
 Business considerations
 Cell line considerations
 Process development considerations
 Regulatory considerations
 Technology considerations
A Molecule's Journey Webinar | December 5, 20173

5. 5 A Molecule's Journey Webinar | December 5, 2017
Business considerations
Speed to Clinic
No revenues before approval
Time is money…
Key decisions to make over the process
Outsource manufacturing to accelerate development?
Out-license a molecule to generate revenues before approval?
Or internalize 100% to keep the value?

6. 6 A Molecule's Journey Webinar | December 5, 2017
Business considerations
Process Efficiency over Speed
No revenues before approval
Time is money…
Speed is key but Process efficiency has to be addressed early
A poorly developed process can backfire in the later stage
Inefficiency can make the drug too expensive to produce
Choosing the right partner is key

8. 8 A Molecule's Journey Webinar | December 5, 2017
Business considerations
Filing Strategy
Filing can be either global or local
Ease of conducting clinical trials
Largest patient populations
Time to obtain approval
Engage Authorities throughout Development

9. 9 A Molecule's Journey Webinar | December 5, 2017
Cell line considerations
Choose the right host

10. 10 A Molecule's Journey Webinar | December 5, 2017
Cell line considerations
Choose the right clone
 Clonality is a requirement for regulations (ICH Q5D)
 Protein quality is clone related
 Robustness is clone related
 Genetic stability is clone related (60 generations)
*Shuangping Shi et al. 2011
Ensure monoclonality thanks
to a Clone Select Imager
To fit with ICH Q5D

11. 11 A Molecule's Journey Webinar | December 5, 2017
Cell line considerations
Bank your Clone
 A Cell Bank ensures robustness over development
 Cell bank establishment takes 28-30 days
 Safety testing is a regulatory requirement
 Cell banking is the first GMP activity

12. 12 A Molecule's Journey Webinar | December 5, 2017
Process development considerations
Efficiency and Viability
 Reliable and reproducible through scale-up
 Reliable and reproducible through scale-down
 Reliable and reproducible through tech transfer
 Consider ease of scalability
 Consider regulatory issues
 Consider commercial issues

13. 13 A Molecule's Journey Webinar | December 5, 2017
Process development considerations
Financial viability over Productivity
Consider the end-product and its expected cost
Cost of raw-materials
Upstream titer
Downstream efficiency
Dose per patient
Medical needs
Determine the optimal yield of your process
Outsource to a trusted partner? Key question

14. 14 A Molecule's Journey Webinar | December 5, 2017
Regulatory considerations
Patient safety
The main driver is to ensure patient safety
Prevent safety issues during clinical development
Assess product effectiveness
Track product isoforms as early as possible
Prevent cross-contaminations

15. 15 A Molecule's Journey Webinar | December 5, 2017
Regulatory considerations
Quality and robustness
Product
quality
Process
robustness
Analytics
Process and
Analytical
Development
HMW
Monomer
LMW
Example: Size Exclusion HPLC

16. 16 A Molecule's Journey Webinar | December 5, 2017
Technology considerations
Flexibility is key
RUN
RUN
Preparation / Parameter setting
Media conditioning
CIP and Storage
Preparation
Preparation / Parameter setting
Preparation
RUN
Stainless Steel Bioreactors
Single-use Bioreactors
Preparation
RUN
Single-use as the new Gold standard
Elimination of clean-in-place
Reduced energy requirement
Reduced time requirement
 Equipment mobility
 Pre-sterilized assemblies
 In-process aseptic connections

17. 17 A Molecule's Journey Webinar | December 5, 2017
Technology considerations
Scalability is key
The use of a bioreactor with proven
scalability is a way to ensure success
through clinical development

18. 18 A Molecule's Journey Webinar | December 5, 2017
Conclusion
1. Critical considerations
 Patient safety
 Product quality
 Process efficiency
2. Key considerations
 Speed to clinic
 Cost of production

19. The life science business of Merck KGaA, Darmstadt, Germany operates as
MilliporeSigma in the U.S. and Canada.
MilliporeSigma and the vibrant M are trademarks of Merck KGaA,
Darmstadt, Germany. Copyright © 2017 EMD Millipore Corporation. All
Rights Reserved. BioReliance is a registered trademark of Sigma Aldrich
Co LLC. BioReliance is an affiliate of Merck KGaA, Darmstadt, Germany.