Viral Products Expertise, Experience and Capability

Transcription

1 Viral Products Expertise, Experience and Capability Partners for Life Advancing tomorrow s medicines

2 w Dedicated viral products facilities Your CDMO partner for biologics and advanced therapies Our state-of-the-art facilities include: The National Center for Therapeutic Manufacturing which is designed for Process Development and I/II GMP production of advanced therapies (Viral, Microbial, Plasmid) The Flexible BioManufacturing Facility which is designed for cgmp production of Viral products 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. 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). Assets for every stage of product lifecycle Our manufacturing assets will support your full product lifecycle - from pre-clinical development to commercial production. Volume Requirements 1L..10 s..100 s of L Pre-Clinical Clinical Trial Production I Launch Commercial Flexible BioManufacturing Facility (up to BSL-2+, BSL-3 capable) NCTM* (up to BSL-2) II III *NCTM = National Center for Therapeutic Manufacturing

3 Unrivalled capabilities and facilities Unique levels of expertise Upstream Development and GMP Capabilities Virus Technology Cell Culture Recombinant Technologies E xperience with multiple viruses and virus vectors A ttenuated, recombinant Adherent Cells icellis Nano, HYPERStack-36, CellSTACK Generating RVB, MVB, WVB Suspension Cells 1-200L SUB V irus titer or genome copy number and total particles determined by orthogonal methods Plaque purification V irus engineering: purification; inactivation; adaptation to cell lines Staff is experienced with rdna technologies including: Transfection Cloning and gene insertion Transduction Adaptation Adherent to Suspension HEK293, Vero 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 Adaptation Suspension to Adherent SF9, EXPI293, EB66, A549 Cell culture adaptation to serum free media Vaccine Expression Systems MP Cell banking G Microbial Mammalian Viral Animal free/antibiotic free-media prep Vaccine Antigen Expression 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 (HEK-293, Vero, EB66) CHO Baculovirus EB66 Herpesvirus Vero Picornaviruses MDCK Flaviviruses A549 Retroviruses HeLa Influenza C ell 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 S ingle 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 ulk Harvest Separations: B Batch & Continuous Centrifugation TFF & HFF Depth filtration ell lysis: C Chemical Homogenization Osmotic Shock Virus sucrose gradient ultracentrifugation ebris separations: D UF/DF Absorption Depth filtration Chromatography platforms: IEX Affinity Mixed Mode HIC SEC EBC Membrane chromatography

4 Stability and Formulation Development Additional Services Methods available to examine virus titer, total virus particles and virus aggregation Fill/Finish Processes (Filtration, Sterilization, Vialing - up to 1000 Vials) 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 (50cm 2 to 2.5m 2 ): Spectrum KrosFlo, Sartorius Alpha, Akta Flux S Production Scale Skids (0.5m 2 to 200m 2 ): 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 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 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 ELISA PCR/qPCR/ddPCR Restriction Analysis DLS particle counts (NanoSight) Biological Potency Assays

5 Belasis Avenue, Billingham TS23 1LH, United Kingdom Tel: +44 (0) J. Morris Commons Lane, Morrisville, North Carolina 27560, USA Tel: +1 (919) Discovery Drive, Suite 200, College Station, Texas 77845, USA Tel: +1 (979) 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. June 2017