Automating Fermentation

INTERPHEX2007
April 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

INTERPHEX2007
April 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

INTERPHEX2007
April 24-26, 2007

The NIMO Project Timeline

2000

2002

2004

2006

2008

NIMO Engineering Kick-Off

Engineering and Design
Procurement
Construction
Commissioning
Validation
BLA Enabling Runs
BLA Submission
FDA Review
BLA Approval

INTERPHEX2007
April 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

INTERPHEX2007
April 24-26, 2007

The Fermentation Process Overview

Feed Vessel (for Large Fermenters)
Inoculation

CIP/SIP
Pressure Control
Media

Additive

Sparge
Sampling
Base

INTERPHEX2007
April 24-26, 2007

S88 Control Modules

Identify the common modules and instances.
Examples:
Motors
Valves

INTERPHEX2007
April 24-26, 2007

S88 Equipment Modules

Added some area-specific
module templates
Fermentation Agitator Control
Fermentation Pressure Control
Fermentation Temperature
Control
pH Control
Dissolved Oxygen Control
Foam Control

Used some project-wide

module templates
Sampling System
Sparger Control

Added unique (one-time

use) equipment modules
Transfer Panels
Valve Assembly (VA) Control

INTERPHEX2007
April 24-26, 2007

Transfer Panel

INTERPHEX2007
April 24-26, 2007

S88 Units
Identify classes and instances based on..
Physical similarity
Phases that they use

Batch Media
Inoculate
Ferment
Etc.

INTERPHEX2007
April 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

INTERPHEX2007
April 24-26, 2007

Pre-SIP Pressure Test

Seed Fermenter
Pre-SIP Pressure Test
Production Fermenter
Pre-SIP Setup
SIP Sample Line
SIP Production
Fermenter
SIP Inoculation Line

Recipes
1) Group Phases into
Operations
2) Group Operations into
Unit Procedures
3) Group Unit Procedures
into Procedures

INTERPHEX2007
April 24-26, 2007

Vessel to Vessel Communication

Are you ready to receive?
Here comes the transfer.

SEED
FERMENTER

XV
015
XV
016
XV
047
XV
048

XV
019

TP

XV
150

XV
154

XV
152

Yes. Bring it on.

XV
151

T
XV
148

I got it.

XV
070

T
MV
071

PRODUCTION
FERMENTER

XV
015
XV
016
XV
047
XV
048

INTERPHEX2007
April 24-26, 2007

XV
019

Manufacturing Procedures
Material Management
Container Management
Filter Management
Sampling
INTERPHEX2007
April 24-26, 2007

MAT 2.
200 GR

Testing
Emerson and Genentech
worked together closely on
requirements
Emerson performed modulelevel and integrationlevel
testing
Emerson and Genentech ran a
full Customer Acceptance Test
(CAT) prior to delivery

INTERPHEX2007
April 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.
INTERPHEX2007
April 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.

INTERPHEX2007
April 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.
INTERPHEX2007
April 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.
INTERPHEX2007
April 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.
INTERPHEX2007
April 24-26, 2007

Right-Size

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

INTERPHEX2007
April 24-26, 2007