Manufacturing Cell Based Therapies

using Modular Facilities

Mike KatsisG-CON Manufacturing Inc.

2

The Current Scenario

The Needs

The Possibilities

The Examples

Conclusion

Agenda

3

The Current Scenario

Expression rates go up, therapies are changing, which results in lower volume, smaller footprint, higher flexibility site needs

Multi-product, multi-purpose sites are required to serve the biosimilar area. This also leads to more robust single-use process technologies and cleanroom segregation

Regulatory view is changing and supporting agile, efficient and flexible manufacturing platforms

Traditional sites cannot accommodate new therapy processing needs, which require:

• Fast deployment, scaling and mobility

• Robust containment and segregation

• Decontamination possibilities, in conjunction with appropriate cleanroom construction materials

4

The Current Scenario

“Until now, modular facilities have reproduced traditional architecture with regard to embedding utilities piping and HVAC ducts in the interspace between the physical module limits and the suspended ceiling making refurbishment, if required, extremely complicated.

The new approach is to segregate pre-assembled modules into laboratory and utility modules, which are designed such that they permit even simpler and faster construction, qualification, validation and maintenance, respectively….” Alan Pralong (2013)

sameinflexibility

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The Current Scenario, cont.

• High CAPEX/higher OPEX

• Long time-to-run (2-4 years)

• Large volume, product dedicated

• Scalable only with disruption of running processes and re-qualification

• Extensive qualification needs

• Difficult containment, lack of segregation due to interconnected ductwork

• Difficult to sanitize

• Difficult to clone, since materials and labor change every time

• Immobile w/o option to relocate

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Regenerative/personalized medicines require specific processing systems in accordance with any possible logistic hurdles and robust containment needs

The Current Situation – Questions

Courtesy of GSK (2016)

Courtesy of Novartis (2015)

Questions prevail:How to produce ? Where to produce ? How to release ?

How to control ? How to multiply ?How to ship ?

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The Needs

Changing Therapies require Changing Mind-sets in Processing & Facilities & Logistics

10,000L – 15,000L mL – 50L

Terminal sterilization by filtration Potentially only processed in closed aseptic process

Large patient population Individual patient based

Long development & planning cycle Rapid deployment

Inventories Patient based immediate supply

Time for release studies Immediate, rapid release

to name just a few differences….

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Centralized or Decentralized ?!?

The question of centralized or decentralized (hospital, cancer center, local based, logistics hub, airport location) is still debated (needle to needle logistics for example)

Centralized (hub)

Decentralized (hospital or cancer center)

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Start Centralized and Check…

If the facility allows to start Centralized and after the initial investigation to Decentralize, the investment needs can be delayed or the structures can be leased

Centralized (hub)Decentralized (hospital or cancer center)

Take apart

Re-assemble

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The Needs – Scaling w/o Interruption

Flexible scalability, utilizing mobile autonomous cleanroom units reduces interruption of existing processes and can delay investment decisions

*simplistic schematic

Shell Building

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The Needs – Cloning (globally & locally)

Cloning of Facility Platforms means Faster Deployment & Time-to-Run

24’ x 30’

Learning from the 1st built

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Prefabricated Possibilities

Individual or clusters of prefabricated units are available Benefits:• Rapidly deployable

• Mobile

• Repurposable

• VHP sanitizable

• Robust containment

• Segregated

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Existing Future Facility Examples

Prefabricated OSD Site Prefabricated Aseptic Filling Site

Courtesy: Pfizer Courtesy: University of Tennessee

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Conclusion

Current, prevalent facility/process designs become outdated and strain to meet pressing industry requirements and application needs

Facilities require to adopt mobility in case of processing and location decision delays

”Platinum standard” aseptic processing requires to be accommodated within robust and strict containment options

Multi-product/multi-purpose facilities become a prevalent request to gain capacity utilization

Facility deployment requires much faster (< 1 year built), mobile and possibly clonable

Thank you !

“The arrogance of success is to think that what you did yesterday will be sufficient for tomorrow” William Pollard

mkatsis@gconbio.com