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Transcript of Changing the Paradigm: How Biogen tech transfers processes into our disposable manufacturing...
Changing the Paradigm: How Biogen tech transfers processes into our disposable manufacturing facility
Marcelo Anderson
Manufacturing Sciences
Biogen
Agenda
Technology Transfer Defined Scope & Thesis Technology Business Processes Technology Transfer Possible Next Steps Questions
Disposable Equipment
Flexible Facility
Understand Your Asset
Facility SchedulingTeam Structure
Streamlined Processes
Simplify
Information
Decision Making
Process Technology Transfer
Transfer all the knowledge needed to perform a given biotech process from a Transferring Site to a Receiving Site- ISPE 10 September 2009, Herwig Kapeller, Novartis
Pharmaceuticals Corp.
Also includes - Responsible for the successful production, disposition, stability and product comparability from transferring site to receiving site.- Biogen Global Technology Transfer
Scope & Thesis
Scope – early clinical (FIH/I/II) production of recombinant biotherapeutics with mammalian cells
Thesis – the right technology+ business systems+ Tech Transfer allows for transformational performance -> >75% improvement
Technologies: Strategy
5
Fully compliant for phase Keep it simple Keep it flexible Make equipment identical to pilot plant Innovate – within and piloting Make it differentiated
- Capability- Capacity
Technologies: Applied
Disposable Equipment• Disposable• Adaptable - on and off platform• Closed
Flexible Facility• Stand alone• Small footprint• Innovation space• Clinical: Pre FIH, Phases 1 to 2
Understand Your Asset• Understand advantages• Differentiate• Innovate
Understand Your AssetFVM vs SSM (Titer – 4 g/L)
Breakeven point ~ 8 kg
Disposable Equipment
A.Shukla et Al (2012), Vertical Integration of Disposables in Biopharmaceutical Drug Substance Manufacturing. BioProcess International 10(6)
1,000L
Detergent Viral Inactivation
Low pH Viral Inactivation
Flexible Facility (FVM)
Four clinical campaigns completed successfully demonstrating proof of concept ISPE Facility of the Year Award 2013
- 10,000 square foot facility in RTP utilizing upstream and downstream single-use technologies
- Closed process from inoculum prep through final drug substance bagging.
- Approach designed for speed and adaptability which enable transformational improvement
Business System: Strategy
10
Change Control Rigidity
Commercial cGMP
Development Pilot Plant
Tox MaterialTraditional SS Clinical
?FVM
Fully compliant Keep it simple Use original sources of data Innovate
FVM
Business Systems: Applied
Facility Approach and Scheduling• Adaptability/$ to failure• On demand production• Organized like pilot plant
Team Structure• Self directed team & independent • Commitment/expertise on the floor• Increases equipment flexibility
Streamlined Processes• Standard document templates• Alignment between groups• Optimized tech transfers
FVM Facility Thought Processand Scheduling
R to D Transition
IND Filing IMPD’s
Q1 Q2 Q3 Q4 Q5 Q6Process Development
Raw Material Procurement/ TT Bulk Mfg
DS Release
DP Fill
DP Release
Stability
Pack / Release
Tox Study + FIH ProtocolTox-pilot F/RNon-GMP
GMP
Industry Standard: Approximate Timeline from Cell Line Selection to IND: 18-24 months
IND Filing IMPD’s
Q1 Q2 Q3 Q4 Q5 Q6
Process Dev
RM Procurement
Bulk Mfg
DS / DP Release
Stability
Tox Study
Pack / Release
DP Fill
GMP
FVM Thinking: Approximate Timeline from Cell Line Selection to IND: 10 months
Non-GMP
Bulk Mfg
DP Fill
FIH Protocol
DS / DP ReleasePack / Release
FVM Team Structure -Integrated Operations Unit (IOU)
Common GoalRapid Supply of Clinical Material
Leadership•Drive Vision
•Develop Business
Quality•Compliance
•QA Sys.
Systems•Documentation
•Knowledge Management
Operations•Production•Concept
Deployment
Planning•Schedule• Inventory
Technical•Process Expertise
•Single Use Sys.
RTP MFG
13
Rotation
• All members co-located on the production floor
• Diverse skillset• Senior Mfg. Associates• Engineers• Scientists• Junior staff with high potential
• Team is empowered to make decisions / create new business processes
On the Floor
Team Structure - Applied
MFGMSTD
Ex. Brx Inoculation & BPR Review
QATech (MS)
Systems (Doc) MFG
Ex. BPR Issuance & Review
Rotation
On-the-floor Issuance
Local Inventory
Real-Time Transactions Production
BPR Review
Hours
Real World Examples – Not Staged
15
FROM TO
Conventional tech transfer Seamless knowledge transfer
“Line function centric” approach
Nimble “product centric” approach
Multiple hand-offs Minimal hand-offs
Application of commercial- centric systems for all programs
Adopting flexible/simplified system for clinical programs
a new operating model, where an accelerated approach for early phase drug development is realized. Our clinical supply chain is optimized so that cGMP compliance lives comfortably alongside the flexibility required to enable rapid delivery of clinical supplies.
It is a model that dissolves the existing functional operating boundaries in the transition of clinical programs. Success means, every individual’s contribution increases the opportunity to advance more drug candidates.
Tech Transfer Process: Strategy
From “Clinical Supply Transformation New Business Model” September 2011Kasra Kasraian, Rhonda Sundberg, Steven Doares, Adam Sheriff, Tom Holmes, Ian Rosenblum, Rick Shansky, Andre Walker
Tech Transfer: Applied
Simplify• Focus on the critical / eliminate unnecessary• Minimize membership• Same equipment throughout
Information• Centralized information done once• Automatic record creation• Information ownership clarity & empowerment
Decision Making• Reframing Risk• Transfer decisions / ownership• Team of 4
Simplify
Traditional Transfer Characterize platform & Process
screening Lab work to manage differences Confirm at pilot & full scale Ensure comparability Rapid deployment Minimize risk to ensure schedule Product stability + phase 1/2
material Typical transfer 12+ months &
>$2.5MM Team – dozen+
FVM Transfer 3L only
Take the risk FVM is full scale Nothing to compare to Minimize deployment Schedule adjust to success +Tox
4 weeks & $50K
Team - 4
Information
Template batch records decouple process description from operational instruction Minimizes resource burden responsible for documentation development Minimizes timelines (non-iterative development & independent review process)
Template batch records adapt to unpredictably of an early clinical processes Provide increased flexibility at expense of being less prescriptive Requires knowledgeable staff to execute (ex. normalized values)
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PFD Development
PFD Approval
Record Development
Record Approval
Record Issuance
Process Description Revision CycleBatch Production Record
PFDRecord
Unit Op Instruction
Materials Table
Clinical Comments
Source for operational parameters Empowers staff with process
knowledge
Modular, semi-chronological form Serves as activity log Flexibility for real-time change
Decision Making
19 http://teams/sites/FVM
Empowered team of 4- Representation- Similar to development
Notes- Communication ease- Empowered for decisions- Readies team for decisions- Need right personalities
Summary
Disposable Equipment
Flexible Facility
Understand Your Asset
Facility Scheduling
Team Structure
Streamlined Processes
Simplify
Information
Decision Making
Possible Next Steps
Velocity- R to MFG, no passing D- 6 month supply chain - +DP/LP- Throughput - Multiple purification areas- Disposable continuous chromatography
Scheduling- On-demand- Disposable buffer concentrates
Simplicity- Replace depth filtration- 60cm disposable column
Acknowledgements
Rich Guerra Mark Chen Shane McCarroll Chad Cooper Matt Haines Chris Antoniou Jack Kane Venkatesh Natarajan Scott Keetch
Matt Westoby Phil Vilmorin Devin McCann Diana Brown Mike Rogers Lynn Conley Sanaa Elouafiq