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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OUR MISSIONTo Serve Patients

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AMGEN IS LEADING THE WAY IN TRANSFORMING THE MANUFACTURING OF TOMORROW

Today • TomorrowYesterday

http://10.216.221.128/gallery2/main.php?g2_itemId=11793&g2_imageViewsIndex=1

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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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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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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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• 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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• 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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100

200

300

400

500

600

ConventionalFacility

Singapore

Energy Use (Gigajoules per kg

produced)

0102030405060708090


Singapore

CO2 Emissions(Metric Tons per kg

produced)

0

50

100

150

200

250

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Singapore

Water use (1000 gallons per kg

produced)

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0.1

0.2

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AML6 Singapore

Solid Waste (Metric Tons per kg

produced)


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Regulatory filings FDA, EMA, CH, CA, TGA Completed!

PROCESS PERFORMANCE QUALIFICATION COMPLETED 29 MONTHS AFTER LAND ACQUISITION

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• 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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• 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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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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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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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

2 3

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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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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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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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5 73

6 85

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M O N T H 1 M O N T H 2 M O N T H 3 M O N T H 4 M O N T H 5 M O N T H 6 M O N T H 7 M O N T H 8 M O N T H 9 M O N T H 1 0 M O N T H 1 1 M O N T H 1 2

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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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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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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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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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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THANK YOU!

introducing flexible manufacturing into the...

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