Post on 01-Dec-2015
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
Automating FermentationAutomating Fermentation
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
Presenters
Todd Ham– Automation Engineer
Emerson Process Management, Life Sciences, Food, and Beverage
Todd Edgington– Automation Engineer
Genentech
NIMO Facility, Oceanside, CA
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
The NIMO Project Overview
• NIMO is a large scale, multi-product biopharmaceutical complex.
• Fermentation/Recovery process– Fermentation– Centrifuges, Chromatography, UF/DF, …– CIP/SIP
• Fully automated– Recipe-level batch control– Warehouse management– Electronic signatures– Electronic records
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
The NIMO Project Timeline
NIMO Engineering Kick-Off
Procurement
Construction
Commissioning
Validation
BLA Enabling Runs
BLA Submission
FDA Review
BLA Approval
Engineering and Design
2000 2002 2004 2006 2008
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
NIMO Philosophy• Fully automated
• Paperless, dock-to-dock
– Electronic record
– Handheld units for plant operations
– Barcode scanning for material additions, filters
• Consistency for operator / Use of industry standards
– Bus technologies
– S88 / S95
• Fermentation was integral to entire project
– Project philosophy impacted fermentation
– Fermentation impacted project philosophy
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
The Fermentation Process Overview
Vent through
roof
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InoculationPressure Control
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Base
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INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
S88 Control Modules
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CMB 3/3/03
CIPR
• Identify the “common” modules and instances.
Examples: Motors Valves
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
S88 Equipment Modules
• Used some project-wide module templates– Sampling System– Sparger Control
• Added some area-specific module templates– Fermentation Agitator Control– Fermentation Pressure Control– Fermentation Temperature
Control– pH Control– Dissolved Oxygen Control– Foam Control
• Added unique (one-time use) equipment modules– Transfer Panels– Valve Assembly (VA) Control
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INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
S88 Units
• Identify classes and instances based on..– Physical similarity– Phases that they use
• Batch Media
• Inoculate
• Ferment
• Etc.Unit Class: Production Fermenter
TP A TP B
Unit Class: Seed FermenterUnit Class: Inoc Fermenter
VAUnit Class: Feed Vessel
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
Phase Control
• Batch Feed Vessel• Batch Fermenter• Pre-inoculation Prep• Inoculate• Ferment• Sample• Add Additive• Add Base• Add Feed Media• Transfer• Pressure Test
• The following CIP Phases for Feed Vessel, Production Fermenter, Seed Fermenter, Discharge Line, and Media Line
– CIP Setup– CIP Circuit– CIP Complete
• Pre-SIP Pressure Test Seed Fermenter
• Pre-SIP Pressure Test Production Fermenter
• Pre-SIP Setup• SIP Sample Line• SIP Production
Fermenter• SIP Inoculation Line
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
Recipes BatchFermenter
Pre-Inoculation Prepare
SIP Inoculum Line
Inoculation
Fermentation
Feed Media Addition
Transfer
Prompt Operator to Run:
Feed Vessel Fill Procedure
Production Fermenter Procedure
To HarvestHARVEST VESSEL
HARVEST
Vessel/Transfer Line WFI Flush
Vessel/Transfer Line WFI Flush
Base Addition
From MediaMEDIA TRANSFER
From Seed Fermenter
TRANSFER
From MediaVESSEL/TRANSFER LINE
WFI FLUSH
From MediaVESSEL/TRANSFER
LINE WFI FLUSH
Additive Addition
Prompt Operator to Run:
Media Feed CIP/SIP Procedure
Feed Addition
From MediaMEDIA TRANSFER
Wait Until Feed Vessel Fill Procedure Completes
Wait Until Media Feed CIP/SIP
Procedure Completes
1) Group Phases into Operations
2) Group Operations into Unit Procedures
3) Group Unit Procedures into Procedures
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
Vessel to Vessel Communication
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PRODUCTIONFERMENTER
TP
Are you ready to receive?
Yes. Bring it on.
Here comes the transfer.
I got it.
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
Manufacturing Procedures
• Material Management
• Container Management
• Filter Management
• Sampling
MAT 2.200 GR
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
Testing
• Emerson and Genentech worked together closely on requirements
• Emerson performed module-level and integration–level testing
• Emerson and Genentech ran a full Customer Acceptance Test (CAT) prior to delivery
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
Lessons Learned – Modularity
• As much as possible, keep process units the same.
• With similar units, make sure operations are as uniform as possible as well!
• Beware of alias over-load.
• Enforcement of classes can be a negative thing.
Unit Class: Seed Fermenter
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
Lessons Learned – Level of Automation
• High levels of automation are a double edged sword.
• With high levels of automation and modularity, documents can become very numerous.
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
Lessons Learned – Up-Front Testing
• Time spent upfront saves on back end effort.
• Easier to fix problems off-site when you are in control of the software.
• Risk based software validation works.
• No level of testing will capture all mistakes or prevent changes.
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
Lessons Learned – Raw Material Handling and other Manufacturing Procedures
• Make sure everyone is on the same page from the start.
• Make sure everyone uses the same language.
• Get operators time on the equipment.
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
Conclusion
• Leverage the S88 model as much as possible.
• Take as much time as possible upfront.
• Prepare for an effort commensurate with your level of automation.
Right-SizeRight-Size
INTERPHEX2007INTERPHEX2007April 24-26, 2007April 24-26, 2007
Acknowledgements
Genentech• Johannes Roebers• Christoph Lebl• Dave Stewart• Sean Stephan• Debi Marshall• Christopher Birnie• Leonidas Castaneda• Jim Merrit• Dirk Ellison
Emerson• Christie Deitz• Craig Bieda• Brian Crandall• Molly Firkins• Dick Seeman• Chen Yang• Shelley Richards• Ajay Savargaonkar• Ketaki Raste