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Innovative Design & Fast Track Project Implementation

Jan Lilja Director

ISPE Nordic

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Agenda

n Case Study: Turn-Key supply of a Modular Aseptic Manufacturing Facility in 17 months n Conclusions

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The Modular Concept An Enabling Technology

n Modular design and fabrication
The term Modular is a wide-ranging concept. In this case it means turn-key supply of complete facilities including all installations, designed, built and IQ:ed off site.

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The Modular Concept An Enabling Technology

n The modular approach is today used for fast track, flexible and predictable turn-key project delivery
- Global process-oriented design solutions (cGMP) - Customized standardization - Integrated validation approach from start of conceptual design

- Off-site construction with higher productivity and predictability - Fabrication takes place in parallel with permitting and groundbreaking work - Same experienced fabrication team independent of final location - Allows for full installation and testing off-site
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The Value of Fast Project Implementation

Same Start with Earlier Completion Date
Fast Track Project Convent ional Project

Faster-to-Market Earlier return on investment Less use of resources Defined/known process

Same Completion Date with Later Start

Less risk at decision point
- Clinical trials results - More info about market conditions - Better developed process
Fast Track Project Convent ional Project

Efficient use of financial resources

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The Modular Concept A Flexible Technology

n Future expansion Phased investment with minimal down-time (Baxter) n Technology Transfer From Center of Excellence to local market Product transfer between identical facilities n Moving the facility Re-sale (Sweden to Grindeks, Latvia), (Vagos, Estonia to BMS, Moscow) Re-location (twice within Sweden, Astra Zeneca) Installation of long lead equipment at vendor s workshop (Astra Zeneca, Genentech)

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Moving the facility

n Cost of relocation
Estimated cost for relocation is about 10-15% of the initial investment (manufacturing building including process, clean utility and HVAC equipment and systems)

n Time schedule for relocation

Estimated time required for relocation is about 4-8 months including disassembly, transport, reassembly and requalification (IQ/OQ)

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Case Study: Turn-key supply of a Modular Aseptic Manufacturing Facility

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The Companys Project Requirements

n The investment should relieve demands on existing facilities and avoid potential delays/shutdown of operations n Design to higher seismic importance (2,5 in California, San Francisco) n Design for 1 batch fill every 24 hours n Install and start 1 pc 28 sqm lyo, prepare for addition of a second n Clean utility generation included in new facility, other utilities from existing site infrastructure

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The Companys Guiding Principles

n Minimize distraction on current projects and Operations Deliver the project using off-site modular facility technology with an integrated project approach Utilize off-site installation of long lead equipment n Utilize vendor standards (engineering, construction and documentation) n Small team that is empowered to make decisions and have access to senior level management Clear and prompt decision making Decisions made within 24 hours n Leverage vendor validation capabilities Risk assessment based approach to validation
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Client Project Objectives

n Deliver a manufacturing facility
Cost to be equal to conventional alternative Speed is a critical success factor On time, through tailor-made, flexible approach Licensed (Fda) in 28 months for $65 M Licensed for 1 liquid product Licensable for full product portfolio Prepared for future expansion
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Project Scope
Size of facility 3,200 sqm, including process areas, mechanical areas for clean utilities and HVAC, lockers,cafeteria, goods receiving area with cold storage - Water pre-treatment equipment (outside of modular building) - 1 WFI still - 1 Clean Steam Generator - 1 Vial washer and sterilizing tunnel - 1 Vial filler - 2 vial cappers - 1 lyophilizer - 2 bulk-prep stations (including glycol cooling) - 1 CIP/SIP station for movable tanks - 6 air handling systems (including automation) - Information management system (batch data collection) GAMP
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17 months from start Detailed Design to OQ complete

ID 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Task Name Revised Plan Project Budget Set Board approval Basic Design Detail Design Fabrication Fill Line testing Pack and ship Support area Pack and ship process area 1st module arrivse on site Permitting Foundation and Site Work Erect modules Re-assembly and start up Qualification through OQ PQ Media Fills Qaul Lots Stability FDA review and approval 1/9 10/17 2005 2006 2007 Oct Nov Dec Jan Feb Mar Apr May Jun JulAug Sep Oct Nov Dec Jan Feb Mar Apr May Jun JulAug Sep Oct Nov Dec Jan Feb Mar Apr May Jun JulAug 2/1 2/8

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Batch division of design and fabrication

n Define and focus on critical areas of the facility n Building separated in support area and process area to allow for simplified access n Building divided into 7 batches n The lyophilization area treated as a separate batch to allow for early dispatch of modules to the supplier of the lyophilizer

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Divide building for simplified access

Process Area

Support Area

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Pre-assembled facility at modular suppliers workshop

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Facility required to blend in with surroundings

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Start-up at the modular suppliers workshop

n The facility was assembled at the workshop (except lyo) n Start-up and FAT of the following systems:
Filling line WFI system CIP system BAS system IMS system

n Tests documented according to GDP to use for validation n Building and Fire official inspections
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Installation of the vial washer

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Start-up of the filling machine

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Testing of the filling line

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Disassembly and preparation for shipment

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Innovative approach
n Move (part of) the facility to the vendor
Use experienced vendor resources Use workshop facilities Use commissioning capabilities (temporary utilities, etc.) Do a thorough debugging and start-up at vendor Make IQ and part of OQ tests in final installation at vendor

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Lyo in a box
To shorten the time schedule and minimize risk and testing, a part of the building was sent to BOC Edwards. The complete lyophilizer system (chamber, condensor and Compressor skid) was installed directly into the modules and all testing was performed in their work shop. Meanwhile the rest of the building was already on it s way to the client s site.

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Project Delivery Geography

Tonawanda

Sweden Holland

San Francisco

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Modules at lyo suppliers workshop

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Modules stacked up with lyo installed

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Facility on final site ready for docking of the lyo modules

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Filling line on site

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FDA approved facility in 27 months

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Achievements
n Able to absorb 3 months schedule delay in permits n Modular building including all process and clean utility equipment designed, fabricated and tested in 10 months n Substantial start up, commissioning and testing completed in the workshops of Pharmadule and BOC Edwards n Training executed and operational documentation completed before shipment to site

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Conclusions
The Modular concept allows for different kinds of FLEXIBILITY
OWNER: - Early finish or deferred start - Allocation period of capital expenditure optimized - Much faster depreciation possibilities of the facility (not fixed asset) DESIGN & FABRICATION: - Customized solution, standardized approach (20/80) - Off-site construction in several locations (executor, vendors) - Batch approach to fabrication (independent blocks) - Independent site preparation work (not on critical path) - Less disturbances for ongoing work on site
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Conclusions
The Modular concept allows for different kinds of FLEXIBILITY
PROJECT TEAM - Less client resources required

- Focus on core competences

* Pharmadule (design, execution, validation) * Vendors (installation & testing) * Client (URS, process, PQ, manufacturing start-up)

FUTURE - Built in flexibility for new equipment/processes

- Ease of expansion with minimal down-time - Re-location at existing or to new site

Result: FLEXIBLE & FAST(ER) PROJECT Implementation

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Thank you for the attention! Questions?

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