optimizing biomanufacturing operations; a study in single-use implementation
TRANSCRIPT
Optimizing Biomanufacturing Operations; A Study in Single-use
Implementation Jeff Odum, CPIP
Biotech SME
What is “Optimization of Biomanufacturing”?
• Use of disposable/single-use devices (68.6%) • Improved process control (67.5%) • Improved analytical testing & product release
(66.3%) • Better process development (63.9%)
12th Annual Survey of Biomanufacturing Capacity & Production, BioPlan Associates, April 2015
The top areas of focus for biomanufacturing organizations optimizing around the implementation of single-use technology
SUS Implementation… • …need not be “all or nothing” (where it makes sense)
• …cost drivers are more than capital costs • …risks include both schedule and logistics
• …may be outside of the QA Group’s box • ……Vendor selection/partnership becomes critical
The things Mom didn’t tell you… Do you really know the drivers/goals of Innovation?
Pluses Neutral Minuses Low capital investment Rely on vendors
No cleaning validation Higher consumables cost
Leachables/Extractables
Inventory storage
Decreased process times Lot /material tracking
Fewer FTE’s Vendor initiated change controls
Easier to transfer/move process
Pro’s & Con’s of Single Use
Where should we Focus?
• Innovation • Efficiency & utilization • Flexibility • Risk
Innovation Radical transformation of manufacturing technology
Technologies enabling end to end continuous processing
Full process understanding and building in quality
Lead times of weeks instead of months
Smaller footprint and increased overall asset effectiveness
Move towards process control instead of end product testing
70%
7 | Manfred Maeder, Markus Krumme | April 2014 | Continuous Manufacturing
Graphic courtesy of MIT
Manufacturing Enterprise
Utilization & Faster Development
8
Flexibility Capability Reliability
Efficiency
Resiliency
Losses
Opportunities Throughput
Achieving Flexibility: Decoupling
9
F
P I
Future
P I
Current
F
Operational Philosophy
• Manual vs. Automated • Time and Motion • The CMO Approach
– Multi-product – Multi-platform
“Knowing” the Knowns and Unknowns
• Process material balance • Multi-product/phase approach • Final equipment vendors • Biosafety considerations • Staff capabilities/roles • User requirements • Raw materials • Storage requirements
A tale of two processes
IN THIS CASE STUDY A BATCH PROCESS IS DEFINED AS GROWTH STRATEGY IN WHICH VESSELS FOR CELL GROWTH ARE CHARGED WITH MEDIA AND THROUGH OPERATION ENSURE ADEQUATE OXYGEN TRANSFER AND MEDIA DIFFUSION WITHOUT A CONTINUOUS MEDIA FEED AND WASTE OR PRODUCT REMOVAL.
IN THIS CASE STUDY A PERFUSION PROCESS IS DEFINED AS A GROWTH STRATEGY IN WHICH VESSELS FOR CELL GROWTH ARE CHARGED WITH MEDIA AND THROUGHOUT OPERATION ENSURE ADEQUATE OXYGEN TRANSFER AND MEDIA DIFFUSION WITH CONTINUOUS MEDIA FEED AND WASTE REMOVAL.
• POTENTIAL OPERATING PROBLEMS WITH TECHNOLOGIES INCLUDING STACK MANIPULATIONS, FLOW MANAGEMENT AND LEAKS
• OPERATOR AND EQUIPMENT SCHEDULING • LOW CELL GROWTH • INCUBATOR FAILURES • HIGH AMOUNT OF SOLID WASTE DUE TO SINGLE
USE MATERIALS • FAILURES DURING ASEPTIC FILLING
• HIGH AMOUNT OF SOLID WASTE DUE TO SINGLE USE MATERIALS
• TIGHT TIME CONSTRAINTS. • EQUIPMENT AND SYSTEM FAILURES • FAILURES DURING ASEPTIC FILLING • POTENTIAL OPERATING PROBLEMS WITH
TECHNOLOGIES INCLUDING CELL CUBE MANIPULATIONS, FLOW MANAGEMENT AND LEAKS
A tale of two processes
A tale of two processes
ANALYSIS FROM A CLINICAL SCALE TO COMMERCIAL SCALE AT ~ 84 LOTS OF 5000 VIALS PER YEAR: (1.35E12 CELLS PER YEAR) • PROTECTED MONOCULTURE CELL LINE THROUGH
USE OF ASEPTIC SINGLE USE EQUIPMENT TO OBTAIN CLOSED SYSTEM AS WELL AS A CONTROLLED CLEAN ROOM ENVIRONMENT.
• FACILITY COSTS ( $22 - 27 MILLION) ~ 25% LESS THAN BATCH CASE STUDY FACILITY
• FACILITY COST DISTRIBUTED ACROSS TOTAL CELLS PRODUCED PER YEAR IS 2.3X MORE THAN BATCH CASE STUDY.
ANALYSIS FROM A CLINICAL SCALE TO COMMERCIAL SCALE AT ~ 20 LOTS PER YEAR: (4.1E12 CELLS PER YEAR)
• EQUIPMENT AND PROCESS OPTIMIZATION TO REDUCE OPERATING
STAFF FROM FROM 20 TO 10 FTES • REDUCE THE HANDLING OF OVER 900 INDIVIDUAL SINGLE USE
COMPONENTS IN A GRADE C ENVIRONMENT TO ~300 INDIVIDUAL SINGLE USE COMPONENTS BY SUGGESTING A BATCH POOLING METHOD
• UNDERSTAND CLIENTS MARKET PROJECTIONS AND ENSURE FUTURE FACILITY BUILDOUT WITH NO INTERRUPTION TO OPERATIONS
• FACILITY COSTS ( $28 – 35 MILLION)~ 25% MORE THAN PERFUSION CASE STUDY FACILITY
• FACILITY COSTS DISTRIBUTED ACROSS TOTAL CELLS PRODUCED PER YEAR IS 2.3X LESS THAN THE PERFUSION CASE STUDY.
A tale of two processes
