Diosynth Biotechnology - FUJIFILM Diosynth Biotechnologies

Diosynth Biotechnology
Biopharmaceutical Contract
Manufacturing
Agenda
• Our Organization
• Experience
• Capabilities and Service
• Regulatory and Quality Compliance
• Collaborative approach
Pharma Business Units
€2.4 bn
Ethical
Pharmaceuticals
€1.1 bn
Active Pharmaceutical
Ingredients
World Wide Presence
Gisors, France
Oss, The Netherlands
RTP, USA
Diosynth Facilities & Locations
• RTP, NC, USA
– Process development labs
– cGMP small scale manufacturing (100-L)
– cGMP intermediate scale manufacturing (2,000-L)
• Oss, the Netherlands
– Process development labs
– cGMP large scale manufacturing (up to 14,000-L
ferm and 25,000-L cell culture)
– cGMP perfusion manufacturing (up to 500-L)
• Gisors, France
– Recombinant insulin downstream manufacturing
Vessel descriptions refer to total volumes throughout
Diosynth Biotechnology Vision
We go beyond the product
• Process development through commercial manufacturing
experience
• Unparalleled execution
• Reputation as a preferred and trusted CMO
• Technical excellence and collaborative approach to
project management
Agenda
• Our Organization
• Experience
• Capabilities and Service
• Regulatory and Quality Compliance
• Collaborative approach
Biotechnology Heritage
• Diosynth Biotechnology, Biologics CMO
– Active as a CMO since 1990
– Over 75 proteins produced under cGMP
– Commercial supply of 4 products
• Organon, Human pharmaceuticals
– 80+ years of experience
– Products in >100 countries
– rFSH
• Intervet, Veterinary pharmaceuticals
– 35+ years biological experience
– World’s 1st rec. vaccine in 1982 (swine dysentery produced in E. coli)
– Largest producer of animal vaccines
• Nobilon, Human vaccines
– Focused on the development, production and marketing of specific human
vaccines
Diosynth Biotechnology
Clinical Programs – Examples*
Process
Dev.
Analytical
Development
Preclinical
Manufacturing
Clinical
Phase I/II
Clinical
Phase III
Validation
Angiostatin - Entremed (P.pastoris)
Endostatin - Entremed (P.pastoris)
PEG-Alfacon - Intermune (DSP, PEGylation)
rNAP C2 – Nuvelo (P.pastoris)
Hsp E7 – Stressgen (E. coli)
huN901-DM1 – ImmunoGen (Mammalian cell)
MAb, HGS (NSO)
V10153 – Vernalis (Mammalian cell)
IL13-PE38 – NeoPharm (E. coli)
Provenge- Dendreon (Baculovirus)
* Publicly available information
Commercial Programs
Process
Dev.
Analytical
Development
Preclinical
Manufacturing
Clinical
Manufacturing
Validation
Commercial
Somavert – Pfizer (E. Coli, Periplasmic)
Puregon – Organon (CHO)
Retavase, PDL (E. coli, IBs)
recInsulin, Diosynth (E. coli, IBs)
Diosynth
rec-insulin
Development and Manufacturing Expertise – Protein
Classes
Y
Few CMOs can
claim a similar
range of diverse
projects
Hormones
MAbs
(link)
Cytokines
Toxins
Therapeutic Vaccines
Receptors
Transcription
factors
Enzymes
Fusion
Proteins
Antiangiogenics
Interferons
Anticoagulants
Expertise - Technology
Development and cGMP
manufacturing across
expression technologies
NS0
Sf21
CHO
Protein Recovery
• Inclusion bodies
• Secreted
• Periplasmic
• Intracellular
HEK
P. pastoris
E. coli
Post Translational
Modification
• PEGylation
• Glycosylation
• Sulfitolysis
Agenda
• Our Organization
• Experience
• Capabilities and Service
• Regulatory and Quality Compliance
• Collaborative approach
Development, Manufacturing and
Analytical Capabilities
• Self-supporting capabilities at both RTP and Oss
• Fermentation
– RTP: small- and intermediate- scales
– Oss: large-scale
• Cell Culture
– RTP: small- and intermediate- scale
– Oss: small-, intermediate-, and large-scales
• Commercial experience at both sites
Services Summary
Tech
Transfer
USP and DSP
Process
Development
Scale-up
cGMP Manufacturing
Stability
Stability
Testing
Testing
Cell Line
Development
Product
Product
Fill and
Finish
Sponsor
Sponsor
Analytical
Development
cGMP
cGMP
Testing
Testing
Process
Development
Preformulation
Development
Validation
Validation
Process Development USP
Cell Culture PD
•
•
•
•
Fed-Batch cell culture development and scale-up
Apply strategies using serum and protein-free media
Perfusion cell culture process development (Oss only)
Design of Experiments software
Fermentation PD
• Fermenters available to test the widest array of process
parameters
• Strategies to maximize yield via high-pressure homogenization or
chemical extraction
• Design of Experiments software
Whether fermentation or cell culture, we offer a seamless transition to
cGMP production and the development of efficient recovery processes
Process Development DSP
Recovery, Downstream, Modifications
•
•
•
•
•
•
•
Variety of filtration methods
Chromatography – Full complement of experience with different media
Purification scale compatible with cell culture and fermentation
Scaled-down models to support viral validation studies
Expertise in protein PEGylation PD and analytics
Inclusion bodies refolding
Design of Experiments software
Technology Transfer Process
• Protocol driven technology transfer
• Conform to regulatory guidance for CMOs (Q7a)
16.12:
– Initiated under contract or formal agreement
– cGMP and quality responsibilities defined
• Successfully implemented our tried-and-true
approach to many projects
– Defined objectives, activities and deliverables for technology
transfer and manufacturing
Choice of Scale - cGMP Manufacturing*
Fermentation
Cell Culture
Oss
14,000L
7,500L
Oss
25,000L
7,500L
650L Perfusion
130L
RTP
1 x 2,000L
2 x 2,000L
1 x 140L
RTP
1 x 2,000L
2 x 110L
*total volume
Downstream
Appropriate
scale
DSP Capabilities
• Full range of chromatographic methods
• HPLC capability
• UF/DF skids
• Explosion proof production rooms
Analytical and Formulation Capabilities
• Full onsite laboratories
• Method development (or transfer)
– Release, In-process, Stability
• Method qualification and validation
• Protein characterization
• Raw material assays
• Formulation development
• Reference standard
characterization
Agenda
• Our Organization
• Experience
• Capabilities and Service
• Regulatory
and Quality Compliance
• Collaborative approach
Compliance Track Record
Examples of Inspections and Audits at RTP Facility:
• EMEA – Product Inspection
08/2006
• CBER – Bi-annual inspection
02/2006
• CBER – Product pre-approval
03/2003
• CDER – Product pre-approval
05/2001 & 11/2002
• Health Canada – On-site
05/2004
• EMEA – Product Approval
10/2002
• >60 Customer Audits
Compliance Track Records
Examples of Inspections and Audits at the Oss Facility:
• DHCI – Routine Inspection
03/2007
• DHCI – Routine inspection
02/2004
• HCAN – Site evaluation
03/2004
• CDER – Product pre-approval
07/2003
• FDA – Product Approval (NCE)
08/2001
cGMP Quality Systems
• Quality Control
–
–
–
–
–
Full on-site laboratories
Raw material and environmental testing
Microbiology testing
Stability testing
In-process control, bulk drug substance and final vialed product
testing
• Validation
– Prepare Process Validation Master Plan
– Perform:
– method validation
– process validation
– cleaning validation
cGMP Quality Systems
• Quality Assurance
–
–
–
–
–
Issue and maintain controlled documents
Certificates of Analysis / Compliance
Disposition of cGMP material
Review and approval of production and environmental control records
Regulatory PAI support
• Regulatory and Compliance
– Prepare CMC sections and support filings (e.g. IND, BLA/NDA)
– Review of client-prepared submissions
– Hosting client audits and inspections by regulatory agencies
Agenda
• Our Organization
• Experience
• Capabilities and Service
• Regulatory and Quality Compliance
• Collaborative approach
Focus On - Project Management
PD/MFG
QC
QA
Sponsor
Sponsor
Product
Product
Engineering
Analytical
Development
CPL LEADS
CORE TEAM
MEMBERS
Project Management
•
Customer Project Leader (CPL) leads Core
Team with representation from each functional
area
•
•
•
Alignment of Client and Diosynth expectations
•
Regularly scheduled communication through
teleconference, meetings and written reports
Joint development of Scope of Work
Overall responsibility for activities, timeline and
budget as defined in the Scope of Work
What is the Business Process?
Select
DB as
CMO
LOI
Sign
Contract
• Core team established
• TT Package
• Scope Development
• Quality Agreement
Initiate
Project
PROCESS TO PROTEIN
EXPERIENCE FULLY EXPRESSED™