FOCUSING ON THE
FUTURE OF
BIOLOGICS
MANUFACTURING
Jeff Odum, CPIP
Biotechnology Lead
Director of Operations
Integrated Project Services
The Tale of…
Speed Racer published by Digital Magna Publishing
Image of “Bigfoot” from National
Geographic Files
Background
3
Process Development/Pilot Plant
Process Development / Pilot Plant
Product
Function
Regulatory:
Description
Operational Scale
Facility Size, sq ft
Cell Culture Trains
Bioreactor Size, L
Capture Column Size, m
Wastewater Generation, Gal/Day
Electrical Power Consumption, kWh/day
Construction Cost, $MM
Project Schedule (weeks) (1)
Design
Construction
Commissioning
Total (yr)
Personnel
Lab
Manufacturing
Clerical, Admin., Mgt
Other (Warehouse, Validation, etc)
Total Personnel
Recombinant protein
expressed in
bacterial or
mammalian cell line.
Technology transfer
from lab to production
environment. Limited
production of drug
substance for early
stage clinical trials
"GMP-like"
Manufacturing
Estimates
Low
High
15,000
1
500
0.3
15,000
5,000
10
35,000
3
2,000
0.5
45,000
10,000
25
15
25
12
1
25
35
20
2
15
10
8
15
48
40
20
15
18
93
Factors
Construction Cost
Land Area, Acres
Regional / Municipal Factors
Land Cost
Labor Cost
Highly Trained Labor Force
Proximity to University Research Centers
Proximity to Gov't R&D and Reg. Centers
Proximity to Airports
Proximity to other Biotech Companies
Proximity of Support Businesses (2)
Public Services Infrastructure (4)
$18MM
5
$40MM
10
Relevance (3)
Low
Low
High
High
Moderate
Moderate
High
High
Moderate
GMP Production Facility
Process Development / Pilot Plant
Product
Recombinant protein
expressed in
bacterial or
mammalian cell line.
Function
Technology transfer
from lab to production
environment. Limited
production of drug
substance for early
stage clinical trials
Regulatory:
"GMP-like"
Manufacturing
Estimates
Low
High
Description
Operational Scale
Facility Size, sq ft
Cell Culture Trains
Bioreactor Size, L
Capture Column Size, m
Wastewater Generation, Gal/Day
Electrical Power Consumption, kWh/day
Construction Cost, $MM
Project Schedule (weeks) (1)
Design
Construction
Commissioning
Total (yr)
Personnel
Lab
Manufacturing
Clerical, Admin., Mgt
Other (Warehouse, Validation, etc)
Total Personnel
15,000
1
500
0.3
15,000
5,000
10
35,000
3
2,000
0.5
45,000
10,000
25
15
25
12
1
25
35
20
2
15
10
8
15
48
40
20
15
18
93
Factors
Construction Cost
Land Area, Acres
Regional / Municipal Factors
Land Cost
Labor Cost
Highly Trained Labor Force
Proximity to University Research Centers
Proximity to Gov't R&D and Reg. Centers
Proximity to Airports
Proximity to other Biotech Companies
Proximity of Support Businesses (2)
Public Services Infrastructure (4)
Large slide view is available in the back of this tab.
$120MM
20
$400MM
50
Relevance (3)
Moderate / High
High
Moderate
Moderate
Low / Moderate
Moderate
Moderate / High
High
High
Times, they are changing…
•
•
•
Business Drivers
Impacting Technologies
Greater Demands on Development
•
•
•
Higher Titers
Greater Efficiency
Higher Utilization
Evolution of Biomanufacturing Technologies for
Mammalian Cells
Hybrid Infrastructure:
Stainless Steel (SS) High Throughput
& Flexible (FVM)
Fixed Single Product
Facilities
FDA Guidance
Multi-Prod MFG
Intro of 15KL “6 pack” plants
Fixed Multi- Product Facilities
Flexible
Manufacturing
Intro of Disposable Tech
Next Generation
Bioprocessing
Emerging Contract Manufacturers
1980
1985
1990
1995
2000
2005
2010
2015
0.01 g/L
0.5 g/L
5 g/L
10 g/L
$10,000/g
$1000/g
$300/g
$100/g
Titers
A: 2 g/L
B: 5 g/L
7
Modern Enablers
•
More Productive Processes
•
•
•
•
•
High Cell Culture Yields
Skid Enabled
Continuous Processes
Fewer Downstream Unit Operations
More Efficient Downstream Processes

•
Single Use Systems
•
•
•
Simulated Moving Bed Chromatography
Lower Cleaning & Validation Requirements
Quick Area Turnover
Advanced Infrastructure Strategies
•
•
Process Validation (Design Space)
Quality By Design – Solve Future Problems Early
Biomanufacturing Tomorrow
Vision
Develop flexible manufacturing capacity based on disposable
technology that can provide bulk drug product for human use
breaking with traditional fixed investment paradigm.
A fully closed flow path from dispensary to the final Drug
Substance container that:
–
Concept
–
–
–
MFG
Network
Can be operated in an open space with no segregation and
reduced overall environmental control, requiring minimized
fixed assets
Is portable
Is accompanied by phase appropriate quality systems
Provide a low capital cost option for early clinical
manufacturing that can graduate to commercial use.
Enable a hybrid manufacturing network of traditional fixed SS
and disposable single use bags that can strategically be located
across the globe to optimize flexibility and cost structure for:
– Commercial, Late Stage, Early Stage, Biosimilars,
External/Internal Products
9
Manufacturing Challenges/Opportunities
•
Multiphase Opportunities
‒
−
More Products
•
Biosimilars
•
Therapeutic Families
•
ADM Business Models
Faster, Faster
•
Faster Product Lifecycles
•
Advances in Clinical Designs
•
Less “Tech Transfer”
Manufacturing StrategyLess Capital Intensive & Faster Delivery
Capital Investments Comparison
CapEX ($M)
Greenfield
Expansion
Disposable (2x 1KL + 2P)
4.4x
1
Fixed (3x 2KL + 1P)
5.6x
3.4x
Fixed (6x 15KL + 1P)
15.6x
10.6x
Design Features of “Speed Racer”
•
•
•
•
•
•
Closed system processing
Controlled non-classified space
(CNC)
Non-segregation of operations
Upgradable in future for classified
space and dedicated filling area
Fully disposable
Integration with existing facility
operations (hybrid)
Large Operating Spaces
•
Opportunities
•
•
•
Resilience
•
•
Interactions
Reliability
•
•
SUS Problems
Throughput
•
•
Multi-product
Multi-phase?
Failure Interaction
Efficiency
Matrix Operating Spaces
•
Opportunities
•
•
•
Resilience
•
•
Independence
Reliability
•
•
SUS Problems
Throughput
•
•
Multi-product
Multi-phase
Failure Separation
Efficiency
Closed System Operations
‘Closed’ System
Can be described as ‘a system that when operated under normal
conditions prevents the ingress or egress of adventitious agents’
•
This could be met in several ways to ensure microbial control
from production environment
• Aseptic welding
• Aseptic connectors
• Pre-sterilized components / equipment
• Pre-sanitization with acid or base
• Pre-assembly in ‘classified’ area
•
Reduces / eliminates the need for expensive ‘controlled and
classified’ cleanroom environments.
•
Closed system verification was successfully completed
• Use of vendor qualification data in conjunction with
• Assembly of closed system, sanitization and controlled transfer
of growth promoting media for each unit operation
The Future
Some Lessons for Speed Racer…
•
•
•
•
•
•
•
•
•
•
•
Dual source of suppliers for all components whenever possible
Compatibility of components
Supplier relationship and previous experience critical
Get the supply chain folks involved early; they need to understand
the challenges/issues
Get the validation/quality folks involved early; they have to be on
the same page
Qualify additional vendors
Biggest companies are not necessary the best
 Vendor A bag with Vendor B connectors
Use suppliers with local support or local presence
Tube Management
Dealing with the waste
Training
Thank you for your attention
jodum@ipsdb.com