Sustainable bioproduction of the blue pigment indigoidine ...
INTRODUCING FLEXIBLE MANUFACTURING INTO THE...
Transcript of INTRODUCING FLEXIBLE MANUFACTURING INTO THE...
Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
EXECUTIVE DIRECTOR, GLOBAL OPERATIONS LEADER
CHRISTOPHER K. CROWELL, PH.D.
INTRODUCING FLEXIBLE MANUFACTURING INTO THE WORLD OF BIOTECHNOLOGY: CONSTRUCTING THE HIGHLY RECONFIGURABLE FACILITIES OF THE FUTURE
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
OUR MISSIONTo Serve Patients
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
AMGEN IS LEADING THE WAY IN TRANSFORMING THE MANUFACTURING OF TOMORROW
Today • TomorrowYesterday
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
Cost, speed and flexibility have become key differentiators
OUR FOCUS IS TO ENSURE SUPPLY; BUT NEW CHALLENGES OFFER OPPORTUNITIES TO IMPROVE
• Low competition, high margin environment
• Creating capability to produce sufficient biological product was greatest challenge
• Maturing capabilities in manufacturing and process development platforms
• Ready access to biomanufacturing capabilities through CMOs
• Biosimilars, new modalities • International expansion, patient experience• Increasing cost pressure from patients and
payers
• Increasing competition with downward cost pressures
• Drug product capabilities progressively more differentiating
Past Present
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
NEXT GENERATION BIOMANUFACTURING ENABLES FAST AND FLEXIBLE OPERATIONS TO MEET CHANGING NEEDS
Conventional Flexible Key Enabling Technologies
• High titer processes
• Single-use systems
• Modular design and construction
• Connected processing
• Online / At-line analytics
• Real-time remote monitoring
• Raw material variation control
Source of illustrations: Next-Generation Facilities for Monoclonal Antibody Production, N. Guldager, Pharmaceutical Technology (July 2009)
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
WE ARE ADDING FLEXIBILITY TO OUR MANUFACTURING OPERATIONS WITH THE INVESTMENT IN AMGEN SINGAPORE
RT-MSPM technology is improving our process understanding and enabling holistic proactive monitoring
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Providence Business News “Innovation of the
Year in Healthcare”
2010 Award
Real-time monitoring deployed as a visual factory on the mfg floor
Single-use technologiesModular with
Connected ProcessingReal-time Remote
Monitoring
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
• This investment will enable us to dramatically increase our “bulk” production
capabilities vs conventional alternatives– 1/4 of the capital cost; 1/2 of the construction time; 1/3 of the operating expense
• Benefits:– Added flexibility in establishing manufacturing sites– Estimated cost reduction of 60% or more per gram of protein– Achieves savings of hundreds of millions of dollars vs conventional technology
WE ARE ON TRACK TO LAUNCH OUR NEXT GENERATION BIOMANUFACTURING TECHNOLOGIES IN 2017
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
• Less water for heating, cooling, and cleaning of equipment• Smaller facility and HVAC design
DESIGN AND TECHNOLOGIES SIGNIFICANTLY REDUCE AMGEN’S ENVIRONMENTAL IMPACT
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ConventionalFacility
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Energy Use (Gigajoules per kg
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
Regulatory filings FDA, EMA, CH, CA, TGA Completed!
PROCESS PERFORMANCE QUALIFICATION COMPLETED 29 MONTHS AFTER LAND ACQUISITION
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
• High cell culture productivity in small bioreactors– Significantly reduces facility footprint
• High utilization of single-use equipment– 95% of product contact surface is single-use
• Connected purification processing– Eliminates product pools between unit operations
• Integrated manufacturing layout– Smaller facility impact to process and equipment changes
AMGEN’S RECONFIGURABLE MANUFACTURING SYSTEM IS CENTRAL TO BASIS OF DESIGN
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
• Closed operations– Aseptic connectors or aseptic tube welds– Gamma-irradiated components and tubing– No process transfer piping
• Single-use equipment– No process transfer piping– No stainless steel hold tanks or reactors in central suite– 95% reduction in surface area requiring cleaning
FACILITY DESIGN AND OPERATION MITIGATES RISK OF PRODUCT CONTAMINATION
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
RELIANCE ON NEW TECHNOLOGIES AND SUPPLY CHAIN(S) REQUIRES A FOCUSED EFFORT TO ENSURE QUALITY
SRM
SRE
• All raw material suppliers• Performance monitored and
through scorecards• Periodic Operating reviews
Supplier Relationship Management is not a new concept but aspects of our program are new to this industry
• Strategic relationships
• Continuous intense engagement
• Shared investment and value
• Open two way feedback
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
AMGEN APPROACH TO MITIGATING RAW MATERIAL RISK—FOCUS ON THREE KEY AREAS: PEOPLE, PROCESS, AND TOOLS
Organization Process Technology
Increased understanding of total supply chain
Leverage best practices from other industries to develop premier solutions for the pharmaceutical/device industry
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
Complete transparency and synchronization of supply
chain
Outputs • Line of sight• Lot definition• Optimized inventory• Reliable supply• Reduced Waste
Supply ChainOptimization
Mutual technical understanding of key raw
materials, their manufacture, use, and interactions
Outputs• Raw material and process
characterization• Clear, critical attributes and
specifications• Improved in-process controls• Aligned Quality systems
Intense Technical Engagement
PROCESS—SRE FRAMEWORK IS DESIGNED TO IMPROVE QUALITY, INCREASE RELIABILITY, AND DECREASE VARIABILITY
Collaboration with well defined teams and continued focus at the executive level
Outputs• Joint goals• Regular executive reviews• Clear communication channels• Two way feedback• Sharing of benefits
RobustRelationships
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Multi-Tier Transparency
ITCV and MVA Supplier Lot Genealogy Total Cost of Ownership
Operational Excellence is pursued in all three elements to create value
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
PROCESS—MAINTAINING SUPPLY CHAIN SECURITY THROUGH QUALITY SYSTEMS
Supplier Audits
Supplier Quality
Agreements
Supplier Approval
Supplier Status
Supplier Selection and Approval
Material Qualification and Approval
Monitoring and Continuous Improvement
Specification Development
Material Classification
Material Qualification
Material Commerciali-
zation
Supplier Change
Notifications
Supplier Performance Monitoring
Supplier Investigations
Supplier Relationship
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
A LARGE PART OF TECHNICAL ENGAGEMENT INVOLVES ITCV (IDENTIFY, TRACK AND CONTROL VARIATION)
Identify CriticalRMs and Attributes
Exchange and Trend Critical Information
Correlate with Amgen process
(if possible)
Understand how to Control
Variation
Identify and Implement
Improvements
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
WE EMPLOY A RISK BASED APPROACH WHEN QUALIFYING SINGE-USE EQUIPMENT
Ding, Weibing: Determination of Extractables and Leachables from Single-Use Systems, ©2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Chemie Ingenieur Technik 2013, 85, No. 1–2,186–196
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
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WE TRACK SUS DEFECTS RATE BY SUPPLIER OVER TIME – THIS HELPS IDENTIFY AREAS OF FOCUS
Total Used + Defects 282 1063 1232 219 5 46 376 915 798 758 1025 1009
Total Defects 23 14 21 5 0 4 12 32 11 8 17 12
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
EXAMPLE: A PROJECT TO IMPROVE THE PACKAGING DESIGN FOR THE 2K SUB
A project is underway to redesign and qualify 2K SUB packaging in order to:
• Optimize box size to reduce bag damage during packing process
• Improve packing procedures to minimize variability• Develop understanding of temperature requirements for
shipping & storage
• Improve box strength
• Improved ease of removal for impeller base packaging
• Maintain on carrier sterilization
Status:• Packaging and sterilization qualification testing has
been conducted• Supplier change notification received for implementation
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
EXAMPLE: REDUCE RISK AND MITIGATE FAILURES OF 2K SUB A MULTI-YEAR EFFORT
Goal: Mitigate failure modes in 2K SUB through design changes to the film, tri-seam angle, hanger cutouts, and spargeT design
Year 1 Year 2 Year 3
D J F M A M J J A S O N D J F M A M
Kaizen & Technical Redesign
V&V for film, angle, hanger & sparge T
Amgen integrity, E/L, & kLa testing
Order, Build, and Deliver Bags
Live cell culture runs
Amgen Technical Reports
Specification and site change controls
Use in GMP production
Change Notification
Key Accomplishments for this Reporting Period:• Implementation of new design bag
Next Steps:• Implementation at our clinical site
Current 2K SUB Bag Failure ModesDetached Sparge TTri-seam Failure
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
AMGEN’S RAW MATERIAL TRANSPARENCY FOCUS IS ON TOTAL UNDERSTANDING OF OUR SUPPLY CHAIN
Definitions
“Tier 1” suppliers Direct supplier of goods or services to Amgen
“T2,3,X” suppliers Provides goods or services to Tier 1 suppliers or their suppliers
Node Each supplier’s site associated with a given supplier 1 supplier can have multiple sites (nodes) associated with the materials provided
TX T3 T2 T1
Total Supply Chain Knowledge
Challenge - Introducing this new concept is new to the BioPharma Industry
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
SERVING PATIENTS IS A PRIVILEGE
• This privilege comes with significant responsibilities including providing safe, quality medicines in a robust and reliable manner
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Provided December, 2016, as part of an oral presentation and is qualified by such, contains forward-looking statements, actual results may vary materially; Amgen disclaims any duty to update.
THANK YOU!