Viral Products Expertise, Experience and Capability

Partners for LifeAdvancing tomorrow’s medicines

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Your CDMO partner for biologics and advanced therapies

Good science, experience and a quality driven approach

Cell Line/Strain Development

As your partner, we help expedite this process by bringing our years of experience and our expression platform technologies for microbial expression, pAVEway™; and platforms and solutions for mammalian expression, Saturn™ and Apollo™.

Process Development

At FUJIFILM Diosynth Biotechnologies our Process Development philosophy is driven by designing processes for a wide range of expression systems that result in having phase appropriate product controls that will result in successful process execution during cGMP manufacturing.

cGMP Contract Manufacturing

We offer our partners highly flexible clinical and commercial cGMP facilities for the production, by microbial fermentation and cell culture, of biologics and advanced therapies.

Quality

This is at the heart of everything we do. Quality drives the development and the successful production of your biologics and advanced therapy products from beginning to end, with propriety statistical design tools like RAPTA for Laboratory Process Characterization (LPC).

Pre-Clinical Commercial

Clinical Trial Production

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Flexible BioManufacturing Facility (up to BSL-2+, BSL-3 capable)

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*NCTM = National Center for Therapeutic Manufacturing

PhaseIII

PhaseII

PhaseI

Dedicated viral products facilitiesOur state-of-the-art facilities include:

• The National Center for Therapeutic Manufacturing which is designed for Process Development and Phase I/II GMP production of advanced therapies (Viral, Microbial, Plasmid)

• The Flexible BioManufacturing Facility which is designed for cGMP production of Viral products Phase I-III and Commercial

We are able to offer our partners over 120 years of combined experience in the field of vaccine production and virology.

Our team has a vast range of experience in both research and industry. Our aim is to develop processes based on solid science but with manufacturing scale up ability as the end point. This expert knowledge is the foundation of our Process Development capabilities.

Assets for every stage of product lifecycle

Our manufacturing assets will support your full product lifecycle - from pre-clinical development to commercial production.

Unique levels of expertise Upstream Development and GMP Capabilities

• The Process Development Group has extensive experience with multiple forms of scalable culture for both adherent and suspension cells. Capabilities include: • 1-5 L shake flask • Hyperstacks • Wave Bioreactors • Single-use Bioreactors for high throughput and segregation of suspension cells

• Development/Demo: • Single pass TFF • In line buffer exchange and concentration

• GMP Cell banking • Microbial • Mammalian • Viral

• Animal free/antibiotic free-media prep

• Cell Growth: • HYPERStack 36; Pall ICELLis™ Nano • CO2 incubators, DASGIP 1L reactors,

4 x 10L XDR bioreactors, 4 x 10L Eppendorf BioBLU bioreactors

• 50L XDR, 2 x 200L XDR (all dual purpose: microbial and mammalian)

• Spent Media Analysis for supplementation scheme (Cedex Bio, YSI, HPLC)

Downstream Development Capabilities

• The Process Development group has extensive downstream experience. Capabilities include: • Alternating Tangential Flow (ATF) for process intensity • Pall Micro-24 MicroReactor System

• Dissolvable microcarriers for adherent cells • Single pass TFF • In line buffer exchange and concentration

• Additional capabilities include: • Alternating Tangential Flow (ATF) for process intensity • Pall Micro-24 MicroReactor System • Dissolvable microcarriers for adherent cells

• Bulk Harvest Separations: • Batch & Continuous Centrifugation • TFF & HFF • Depth filtration

• Cell lysis: • Chemical • Homogenization • Osmotic Shock

• Virus sucrose gradient ultracentrifugation

• Debris separations: • UF/DF • Absorption • Depth filtration

• Chromatography platforms: • IEX • Affinity • Mixed Mode • HIC • SEC • EBC • Membrane chromatography

Vaccine AntigenExpression Systems

Virus Replication Platforms

Viruses and Vectors

E. coli Typical Hosts: Adenovirus

CHO HEK-293 Adeno-associated virus (AAV)

Pseudomonas Per.C6 Lentivirus (pDNA)

Yeasts Sf9/Sf21 Poxvirus

Other mammalian Cells CHO Baculovirus

EB66 Herpesvirus

Vero Picornaviruses

MDCK Flaviviruses

A549 Retroviruses

HeLa Influenza

(HEK-293, Vero, EB66)

Unrivalled capabilities and facilities

Virus Technology

• Experience with multiple viruses and virus vectors

• Attenuated, recombinant

• Generating RVB, MVB, WVB

• Virus titer or genome copy number and total particles determined by orthogonal methods

• Plaque purification

• Virus engineering: purification; inactivation; adaptation to cell lines

Cell Culture

• Adherent Cells • iCellis Nano, HYPERStack-36, CellSTACK

• Suspension Cells • 1-200L SUB

• Adaptation Adherent to Suspension • HEK293, Vero

• Adaptation Suspension to Adherent • SF9, EXPI293, EB66, A549

• Cell culture adaptation to serum free media

Recombinant Technologies

• Staff is experienced with rDNA technologies including: • Transfection • Cloning and gene insertion • Transduction

Vaccine Expression Systems

Stability and Formulation Development

• Methods available to examine virus titer, total virus particles and virus aggregation

• Upstream Processing (Expression and Harvest)

• Downstream Processing (Purification) • Processing Hold Steps • UF/DF (Buffer Exchange/Concentration)

• Drug Substance/API Formulation

• Short and Long Term Storage Conditions (Freeze/Thaw Cycles)

• Thermal Excursion

Additional Services

• Fill/Finish Processes (Filtration, Sterilization, Vialing - up to 1000 Vials)

• Custom Cryocycle Development (Cell Bank; Process Intermediate, BDS)

Centers of Excellence

• Viral Vaccines Center of Excellence • Live Attenuated, Inactivated Virus, and VLP

• Plasmid DNA Vaccines Center of Excellence

• Gene Therapy with Viral Vector Development Expertise • Adenovirus • AAV • Retroviral • Replicating/non-replicating

GMP Downstream Capabilities

• Harvest • Hollow Fiber and MF • Batch centrifugation: Beckman Coulter J26XP, • Depth filtration: Pall, Millipore, Sartorius systems

• Ultracentrifugation: (ALFA Wasserman P-KII) experience for flu vaccine development and manufacture)

• Purification • Chromatography (e.g., AAV), SEC, HIC, CHT, MMC

and IEX • GE Avant 25, 150 • GE Akta Explorer and Pure systems • GE Akta Pilot for scale up PD runs • TFF: Hollow Fiber and Cassette • Lab Scale (50cm2 to 2.5m2): Spectrum KrosFlo,

Sartorius Alpha, Akta Flux S • Production Scale Skids (0.5m2 to 200m2): • Membrane Filtration • Depth and clarification grades

Analytical

• Assays can be developed or revised to meet process or product needs

• Fluorescence Cytotoxicity Cell based Potency Assay

• PCR based Identity Testing: from designing primers to identify the viral infection carrying correct insert, or to identify the right correct viral peak in HPLC

• Vector Genome Concentration by Droplet Digital™ PCR or conventional qPCR

• Residual Host DNA by qPCR

• ELISA based Assay for Residuals: Kit Based

• ELISA-based Quantitation of Protein

• Total Protein by Bradford

• Plate-Based Absence of Intact Cell for Content

• HPLC

• HC DNA

• SDS-PAGE/Western Blot

• ELISA

• PCR/qPCR/ddPCR

• Restriction Analysis

• DLS particle counts (NanoSight)

• Biological Potency Assays

June 2017

Email: contactfdb@fujifilm.com www.fujifilmdiosynth.com

Apollo™ is a trademark and the property of FUJIFILM Diosynth Biotechnologies UK Limited. pAVEway™ is a trademark and the property of FUJIFILM Diosynth Biotechnologies UK Limited.Saturn™ is a trademark and the property of FUJIFILM Diosynth Biotechnologies UK Limited.© FUJIFILM Diosynth Biotechnologies UK Limited.

Belasis Avenue, Billingham TS23 1LH, United Kingdom

Tel: +44 (0) 1642 363511

101 J. Morris Commons Lane, Morrisville, North Carolina 27560, USA

Tel: +1 (919) 337 4477

100 Discovery Drive, Suite 200, College Station, Texas 77845, USA

Tel: +1 (979) 431 3500