fast trak customer case study

Imagination at work

Case studies on using manufacturing platforms for mAbs, recombinant proteins, and vaccinesPatrick GuertinGlobal Technical Manager Biomanufacturing Services, GE HealthcarePresented at BPI East, October 6, 2016

Fast Trak your molecule to market

Fast Trak services: rapid market access with total transparency

Cell culture media & supplements

Upstream PD

Downstream PD

Clinical manufacturing

Analytical development/quality control

Process transfer

Training & education

• Medium and feed development and optimization • Rapid Response Production prototypes• Spent medium analysis

• Full upstream process development • Conversion from stainless to single-use cequipment • Scale-up and proof of concept • Bioreactor process optimization • Design of experiments (DoE)

• Full downstream process development • Conversion: stainless to single-use • High-throughput process development • Resin CIP studies • Resin lifetime studies • Design of experiments (DoE) • Viral clearance studies • Scale-up and proof of concept

• Phase I & II manufacturing: 10–2000 L • BSL2 production: 10–500 L • cGMP solution and buffer preparation • cGMP document preparation • Environmental monitoring • cGMP inspection, sampling, release of materials • Quality assurance guidance and oversight

• Method developments• Method transfers • Method qualifications • Reference standard characterization • Stability studies • cGMP lot release testing

• Incoming and outgoing process transfer at any stage • Customer process training • Process documentation • Process gap analysis (site and equipment) • Person in plant (PiP) support • Test methods • Bill of materials

• Standard & custom courses in biologic drug development and manufacturing • Customer on-site access and transparency during all production batches • Hands-on training and education • Process documentation • PiP support

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PD- process developmentCIP- cleaning in placeBSL2- biosafety level 2cGMP- current good manufacturing

Fast Trak experience

> 300 years of collective industry experience (Biomanufacturing Leadership Team)> 100 production campaigns completed> 17 different expression systems utilized> 17 virus clearance studies completed

All projects were converted from conventional to single-use technologies.

Monoclonal antibodies Viruses

Virus -like particles

Fusion proteins Hormones Enzymes

3

In the pursuit of developing innovative therapeutics, biopharmaceutical companies are challenged with:

Risk reduction Drive for cost reduction Aggressive timelines Speed to market

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Case study 1: Biosimilar mAbs, an emerging marketCustomer success through working with global service and technology provider focused on:

Building strong relationships Streamlining technology transfer strategies Single-use technologies Flexible and deployable manufacturing platforms

29230903AA I October 2016

Customer success storySupport of a biopharma customer in reducing risk and increasing speed to market of their target molecules, while working under aggressive timelines

CUSTOMER NEEDS• Design scope of work• Convert from conventional to single-use technologies• Scale-up from 10 L to 200 L, with ultimate target of

2000 L, bioreactor for two biosimilar mAb molecules• Deploy a global, flexible, scalable, cost-effective

biosimilar manufacturing platform under aggressive timelines

• Be first to market in emerging regions• Process transfer to customer’s site in emerging region

CUSTOMER CONCERNS• Aggressive timelines: completion of work in less than

six months• Molecule biosimilarity comparison after process

transfer to single-use technology• Process and equipment design• Protection of customers intellectual property (IP) • Communication with and alignment of global teams• Real-time scope/process changes and definition

phase progressed


Project scope of work

4 × 10 L runs Process

transfer Generation of• protocols• solution

records• bill of materials

Initial scope Another set of 10

L runs were performed

Process transfer Generation of• protocols• solution records• bill of materials

Process confirmation

Scale-up 4 × 200 L runs Generation of• protocols• solution records• bill of materials

Proof of concept

Process scaled from a vial to complete purification of two biosimilar mAb molecules

with the goal to manufacture at 2000 L scale


Technical transfer and conversion to single-use equipment

Upstream process Downstream process

Critical parameters:Seed train, agitation rates, pH, dissolved O2 , sparge pore size, feed, gassing, and bioreactor control strategies.

Critical parameters:Velocities, resin binding capacities, collection criteria, flux rates, temperatures, pressures, pH, conductivity, hold times, storage conditions.


Product A & B: upstream process resultsProduct A 10 L confirmation

run200 L run 1 200 L run 2

Maximum cell density

17× 106 M cells/mL 24 × 106 M Cells/mL 20 × 106 M Cells/mL

Product titer 2.4 mg/mL 3.3 mg/mL 3.2 mg/mLComparable to client data

Low but acceptable Yes Yes

Product biosimilarity confirmation

Confirmed by client Confirmed by client Confirmed by client

Product B 10 L confirmation run

200 L run 1 200 L run 2

Maximum cell density

11 ×106 M cells/mL 10 × 106 M cells/mL 11 × 106 M cells/mL

Product titer 3.4 mg/mL 3.4 mg/mL 3.9 mg/mLComparable to client data

Yes Yes Yes

Product biosimilarity confirmation


929230903AA I October 2016

Product A: downstream process results

Product A 10 L confirmation run

Step recovery

200 L run 1Step recovery


Clarification 86% 88% 88%Protein A +VI 93% 102% 91%Anion exchange 89% 86% 99%UFDF 95% 98% 97%Total process recovery

68% 76% 73%

Comparable to client data

Yes Yes Yes

Product biosimilarity comparison


10UFDF = ultrafiltration/diafiltration29230903AA I October 2016

Product B: downstream process results

Product B 10 L confirmation run

Step recovery



Clarification 84% 85% 93%Protein A +VI 114% 98% 95%Anion exchange 93% 86% 93%Cation exchange 73% 78% 79%UFDF 95% 94% 96%Total process recovery

62% 53% 65%

Comparable to client data

Yes Yes Yes

Product biosimilarity comparison


11UFDF = ultrafiltration/diafiltration29230903 AA I October 2016

Process transfer to customer siteLocal Fast Trak services teams support process transfer to emerging regions, sourcing of local raw materials, and understand local government and regulatory requirements

FlexFactory™ platformKUBio™ facilityContract manufacturerCustomer facility

At GE

FAST TRAK MANUFACTURING SERVICES

Process developmentAnalytical developmentScale-up

Documentation preparationcGMP manufacturingTrain/educate customer team

TransPlant

PROCESS DOCUMENTATION TRAINING START-UPANALYTICAL

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cGMP = current good manufacturing practices

Process transfer to customer siteFast Trak Asia and US teams collaborating/training during the 200 L

production batches

Marlborough, MA, U.S.A.

Logan, UT, U.S.A.

Uppsala, Sweden

Istanbul, Turkey Seoul, S. KoreaShanghai,

ChinaTokyo, Japan

Singapore

Bangalore, India

Project outcomes

Conversion from conventional to single-use technology and scale-up from 10 L to 200 L

Project completed in 5 months (incl. completion of 6 × 10 L batches, 4 × 200 L batches, generation of > 50 process documents, and 4 complete bills of materials.

Customer internal timeline for similar scope of work was estimated to 18 months.

Black box approach to protect customer’s intellectual property (IP) (initially, culture media and feeds, several process solutions, and biosimilarity analytics were unknown).

Succeeded in titer requirement of 3–4 g/L.

Product met biosimilarity requirements.14

KUBio™ manufacturing facilityThe KUBio facility is our turnkey cGMP-compliant process solution for mAbproduction. The modular units are factory-built, final assembly on customer site. Because different parts are developed concurrently, your KUBio facility is fully operational in just 18 to 24 months.

Assembled on brown or greenfield site

Built, assembled, qualified, and ready-to-run within 18 to 24 months

Includes FlexFactory™ single-use platform

2 × 500 L to 4 × 2000 L facilities Segregated up- and downstream

operations, including gowning

15cGMP = current good manufacturing practices

GE Healthcare’s Fast Trak services enable customer outcomes

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Expe

rtis

e

Single-use technologyProcess developmentAnalytical developmentProcess scale-upcGMP manufacturingProject managementTraining & education

Tim

eExperience and expertise to get it right the first timeCross- functional teamsProven technical transfer and quality systems

Flex

ibili

ty

End-to-end services to choose fromTransplant services to customer site with full support

Risk

re

duct

ion

Guidance and oversight from experienced teams

Tran

spar

enc y

Full customer transparencyCustomer actively involved in projectCustomer access to development space

Glo

bal

reac

h

GE’s facilities located all over the worldReach into product and equipment specialistsReach into GE’s global operations

cGMP = current good manufacturing practices


GE, Imagination at work, GE monogram, HyClone, KUBio, FlexFactory, ÄKTA, BioProcess, Cytodex, ReadyCircuit, ReadyMate, ReadyToProcess, ReadyToProcess WAVE, and Xcellerex are trademarks of General Electric Company. ReadyMate is covered by US patent number 6,679,529 B2 owned by Johnson and Boley Holdings, LLC and licensed to GE Healthcare companies. OptiPRO is a trademark of Life Technologies. All other third party trademarks are the property of their respective owners.© 2016 General Electric Company. First published Oct. 2016.GE Healthcare UK Ltd., Amersham Place, Little Chalfont, Buckinghamshire, HP7 9NA, UKGE Healthcare Europe GmbH, Munzinger Strasse 5, D-79111 Freiburg, GermanyGE Healthcare Bio-Sciences Corp., 100 Results Way, Marlborough, MA 01752, USAGE Healthcare Dharmacon Inc., 2650 Crescent Dr, Lafayette, CO 80026, USAHyClone Laboratories Inc., 925 W 1800 S, Logan, UT 84321, USAGE Healthcare Japan Corp., Sanken Bldg., 3-25-1, Hyakunincho Shinjuku-ku, Tokyo 169-0073, JapanAll goods and services are sold subject to the terms and conditions of sale of the company within GE Healthcare which supplies them. A copy of these terms and conditions is available on request. Contact your local GE Healthcare representative for the most current information.For local office contact information, visit www.gelifesciences.com/contact www.gelifesciences.com

GE Healthcare Bio-Sciences ABBjörkgatan 30751 84 UppsalaSweden


http://www.gelifesciences.com/

29230903 AA I October 2016

Medium preparation: XcellerexTM XDUO 100 to 2500 L mixers, HyCloneTM cell culture media

Buffer preparation: Xcellerex XDUO 100 to 2500 L mixers, HyClone buffers and process liquids

Cell culture seed train ReadyToProcess WAVETM 25 systemXcellerex XDR 200 L bioreactorXcellerex XDR 500 L bioreactor

Cell culture production Xcellerex XDR 2000 L bioreactorReadyToProcessTM filter for CFF

Harvestoperations FlexFactoryTM harvestBioProcessTM NFF Pump System

Virus reduction Xcellerex XDUO mixers

Purification operations ÄKTATM ready systemReadyToProcess chromatography columnReadyToProcess filter for CFF

Virus filtration FlexFactory viral clearanceBioProcess NFF Pump System

Bulk formulation and sterile filtration Bulk fill equipment

Fluid management ReadyToProcess portfolioReadyCircuitTM bag and filter assembliesReadyToProcess bins and ReadyCircuit bagsReadyMateTM aseptic connectors

Fast Trak Services Process developmentBridge Manufacturing ServicesTraining and education

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