With the biopharma industry focus on producing biologic and protein based therapies the manufacturing paradigm is requiring a shift from dedicated high volume manufacturing strategy to one that requires flexibility to produce low volumes of high value products in multiple delivery systems. Technologies are emerging that provide not only a high degree of flexibility, but also provide a foundational manufacturing template that can be leveraged to reduce cost and risk. One of the key enabling technologies is the more recent introduction of ready-to-use vials and cartridges, which compliment well established pre-filled syringes options, allows manufacturers to adapt their current manufacturing mindset to one that is more affordable and responsive to current and future pipelines. This presentation will discuss the key market trends associated with the manufacture of biotherapies, automated aseptic processing of pre-sterilized ready-to-use (RTU) containers (e.g. vials, syringes, and cartridges) on a modular manufacturing platform for these products, and experiential based recommendations for implementation of RTU formats in aseptic processes.

1. Adapting Drug Product Manufacturing
Strategy & Processes for Ready-To-
Use Vials, Syringes & Cartridges
Josh Russell
Life Sciences Product Manager, AST
Exploring the Challenges in Parenterals and
Injectables: Manufacturing & Sustainability

2. Presentation Overview
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &
Changing Parenteral Market
Adaptive Manufacturing
Leveraging Ready-to-Use
Considerations & Implications
Summary

3. Parenteral Market Trends
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &

4. Parenteral Market Trends
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &

5. Parenteral Market Trends
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &

6. Pipeline Demands
High value therapies, niche products and biosimilars
are the products of the current and future focus
• Next generation oncology drugs
• Monoclonal antibodies (MABs)
• Therapeutic vaccines
• Gene therapies
• Orphan drugs
• Antigen specific immunotherapies
• Adapted dosages forms
• Recombinant proteins
• Drug combinations
• Cell therapies
Smaller
Batches
Higher Yield
Expectations
Increased
Potency
Market
Volatility
Higher Quality
Expectations
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &

7. New product demands require a
shift in thinking…
• High value / low volume batch production
requires us to take new approaches
– Lean approaches, adaptive “work cells” or “work
centers”
– Maximize utilization, minimize changeover
– Standard modular platforms with reduced lead times
and costs vs. traditional systems
– Easily transplanted to emerging markets
– Adaptive technologies that can be readily customized
to address unique product needs
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &

8. Traditional Approach
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &
 Dedicated brick and mortar productions sites
 Customized to meet immediate product needs with eye to the future
 Difficult to retrofit without disruption
 Dedicated machinery required for vial washing & depyrogenation
 Additional cleanroom space required to house the machinery
 No ability to expand container filling capability (ex. syringe  vial)
 High utility costs
 Container quality defects (e.g. glass breakage, bruising, etc.)
 Product quality risks (e.g. interventions, particulates, etc.)

9. Traditional Manufacturing Strategy
OR
EXPANSION
Fixed
FixedFixed
++
• WFI
• Depyro Tunnel
• Cleanroom
• Validation
• Maintenance
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &
WFI

10. Adaptive Approach
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &
 Modular & “Podular” construction for future adaptation or mobility
 Smaller, reproducible site design
 Adapt to future product portfolio requirements
 Minimizes equipment requirements to the bare essentials
 Equipment is process centric, not container focused (lean)
 Minimal cleanroom footprint
 Utility and labor savings
 Eliminates common quality risks (ex. glass particulation)
 Eliminates common intervention risks
 Enables products to be filled in multiple primary container options
 Adaptive to custom or unique portfolio needs

11. Adaptive Manufacturing Strategy
EXPANSION
Adaptive Adaptive Adaptive
+
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &
<494 Tons
CO2
<58%

12. Enabling Technologies
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &
• Ready-To-
Use (RTU)
• Isolator-barrier
technology
• Single use
materials
• Robotics
Adaptive Manufacturing leverages four proven
enabling technologies to provide a versatile
manufacturing platform

13. Ready-To-Use (RTU)
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &
• Pre-washed &
sterilized containers
– Vials, syringes &
cartridges
– <1 ETU per container
• Packaging eliminates
processing challenges
– Orientation
– Container separation

14. RTU Anatomy
Image courtesy of Ompi
Image courtesy of Schott
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &

15. RTU Minimizes Quality Risks
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &
Images courtesy of Ompi

16. Adaptive RTU Processing
• Small & nimble configured
manufacturing system
• Standard module options
for common processes
• Configure system using
standard modules
– Filling, capping, lyo, tub
opening, bag opening, etc.
– Can be reconfigured for new
requirements
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &

17. Adaptive RTU Processing
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &

18. Processing Considerations
• In-Process Checks (IPC)
– In nest vs. out of nest
• Accuracy & Repeatability
• Packaging
– Static  Particles
– Sterilization Process
• Effects on packaging
– Critical tolerances
– VPHP uptake
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &

19. Processing Considerations
• Container Handling
– In the nest vs. out of
the nest
– Capping
– Freeze drying
• Quality & Regulatory
– Annex 1
– Track & trace
– Interventions
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &

20. Summary
• Rethink traditional aseptic manufacturing options
to determine how well suited for current and future
product portfolios
• Adaptive manufacturing provides the nimbleness
to address immediate and future portfolio
requirements quickly
• Ready-to-use containers reduce total cost of
ownership and common product quality risks
• Partnering with knowledgeable experts is key to
RTU processing success
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &

21. Thank you for your attention!
Questions?
Josh Russell, Product Manager – Life Sciences
Automated Systems of Tacoma (AST)
4110 South Washington Street
Tacoma, WA 98409
(253) 475-0200
jrussell@ast-inc.com
Exploring the Challenges
in Parenterals and
Injectables:
Manufacturing &