Changing the Paradigm: How Biogen tech transfers processes into our disposable manufacturing...

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Changing the Paradigm: How Biogen tech transfers processes into our disposable manufacturing facility Marcelo Anderson Manufacturing Sciences Biogen

Transcript of Changing the Paradigm: How Biogen tech transfers processes into our disposable manufacturing...

Page 1: Changing the Paradigm: How Biogen tech transfers processes into our disposable manufacturing facility Marcelo Anderson Manufacturing Sciences Biogen.

Changing the Paradigm:  How Biogen tech transfers processes into our disposable manufacturing facility

Marcelo Anderson

Manufacturing Sciences

Biogen

Page 2: 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

Page 3: Changing the Paradigm: How Biogen tech transfers processes into our disposable manufacturing facility Marcelo Anderson Manufacturing Sciences Biogen.

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

Page 4: Changing the Paradigm: How Biogen tech transfers processes into our disposable manufacturing facility Marcelo Anderson Manufacturing Sciences Biogen.

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

Page 5: Changing the Paradigm: How Biogen tech transfers processes into our disposable manufacturing facility Marcelo Anderson Manufacturing Sciences Biogen.

Technologies: Strategy

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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

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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

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Understand Your AssetFVM vs SSM (Titer – 4 g/L)

Breakeven point ~ 8 kg

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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

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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

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Business System: Strategy

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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Summary

Disposable Equipment

Flexible Facility

Understand Your Asset

Facility Scheduling

Team Structure

Streamlined Processes

Simplify

Information

Decision Making

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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

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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