Transcript cGMP Manufacturing of Naturally Derived Products

A Unique Manufacturing &
Development Partner
Capabilities Update: 2012
Corporate Profile
BioVectra Inc.
• Privately held Canadian
corporation
• 42 year track record
• 175 employees
• BioVectra is focused on
Pharma and Biotech clients
• Successful FDA audit history
Corporate Milestones
Established in 1970 as
Diagnostic Chemicals
Limited
Opened DCL USA in
1983
Received ISO
certification in 1996
First FDA inspection
was in 2003.
Subsequent inspections
2005, 2007, and 2010
Designed, built, and
commissioned API
facility from 2001 –
2003
Transitioned to GMPs in
2000 as we began to
market our division as
BioVectra DCL
Sale of Diagnostic
division to Genzyme in
December 2007
Expansion of API facility
ongoing during 2010 2013
Our Services
• cGMP custom API synthesis
• cGMP fermentation
• Bioextractions & purifications
• Bioconjugation and MPEG reagents
• Taxane semi-synthesis
• Specialty biochemicals & enzymes
“Bridging Chemistry and Biotechnology”
Ways to Work Together
• cGMP raw material long term supply
• Client-exclusive manufacturing
– 9 of 10 top Major Pharma
– 7 of 10 top Major Biotech
– Mid-sized, Emerging Pharma
• Development partnerships
– Generic co-development
– NCE development & manufacturing technology
cGMP API Manufacturing
• 3 FDA inspected manufacturing
facilities (totaling 85,000 sq. ft.)
• Diverse project scope: research,
clinical, commercial
• History of cGMP manufacturing and
documentation
API Manufacturing Quality History
Food and Drug
Administration
Inspections
• July 2003
• April 2005
• November 2007
• August 2010
Health Canada
Inspections
• January 2008
• September 2008
• March 2011
European Medicines
Agency
• Audit Pending
Japanese Ministry of
Health, Labour and
Welfare
• Audit Pending
Regulatory Support Experience
• 8 DMF Filings
• 1 ANDA
• 2 VMF Filings
• CMC Sections for BLA or NDA
• IND Filing
• Stability Programs
• Method Qualification, Validations, Transfer to 3rd Parties
cGMP API Custom Synthesis
• Pilot equipment from 20L-800L (500g to 10kg)
• Large-scale equipment, 2 x 4,000L (50kg to 300kg)
• Depth of experience in diverse synthetic chemistry
• Experience in producing MPEGs and high-purity
polymers
• Can perform post-fermentation or extraction
chemistry, within a single facility
Analytical Capabilities
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HPLC (RI, UV/VIS, Diode Array Detection, ELSD)
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GLC (FID, TC, Head Space Analysis)
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FT-IR
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NMR (400MHz) - Multinuclear (H, C, Si, etc.)
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UV/VIS Spectroscopy
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Titration (Karl Fischer)
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Wet methods
Melting point
Polarimetry
Coulometric Karl Fischer
Total Organic Carbon
Thermal Gravimetric Analysis
Differential Scanning Calorimetry
Protein Analytical Testing Capabilities
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SDS-Experion
Host Cell Protein
Micro-Lowry (other protein
methods by plate reader)
Enzymatic rate assays
Endotoxin (LAL – Endosafe)
Size Exclusion Chromatography
RP-HPLC
RP-UPLC
Residual solvents
Host cell DNA
Total DNA by Picogreen
BioBurden
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Sterility
Peptide mapping
Protein sequencing
ELISA
PCR
Isoelectric Focusing
cGMP Fermentation
Range of Microbes
• Native and Recombinant
• Marine Based
• Fungal
Types of Drug Products
• Proteins
• Peptides
• Antibodies
• Small Molecules
• High Potency/Cytotoxic
APIs
Project Track Record
• Commercial API product for several major pharmaceutical clients
• Supply of pre-clinical, Phase I, and Phase II material to multiple drug
development companies
• US FDA pre-approval inspection specifically for commercial fermentation
cGMP API Fermentation – Facility
Quality Assurance and Support
• Support projects from preclinical to
commercial scale
• FDA approved facility
• Large range of analytical validation
capabilities
• Full support of CMC, IND, and DMF filings
• In-house stability chambers
• cGMP handling of Master Cell Bank and
Working Cell Bank
cGMP API Fermentation – Facility
Fermentation Equipment - Suite 1
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1 x 20 L and 2 x 30 L
1 x 500 L, 1 x 1,000 L, and 1 x 1,500 L
1 x 10,000 L and 1 x 15,000 L
Schenk centrifugal discharge filter
Alfa Laval BTPX205 centrifuge
Sharples AS26 centrifuge
1 x 500 L and 1 x 10,000 L media tank
1 x 16,000 L filtrate tank
1 x 10,000 L process tank
Dedicated Utilities: clean steam, sterile air, chiller loop, highly
purified water, HVAC (bag in/out)
• Sartorius Hydrosart UF/DF (0.6 m2 to 6 m2)
cGMP Fermentation - Downstream
Fermentation Equipment - Suite 2
• 1,500 L ABEC automated system
• 130 L New Brunswick Scientific automated bioflow system
• Primary fermentors within Class 100,000 area
• Downstream Class 10,000 processing area
• Class 100 biocontainment hood
• Class 100 laminar flow benchtop
cGMP API Fermentation – Downstream
Downstream Processing
• Dedicated project team to optimize end
product yields and quality
• Large scale and diverse chromatographic
capabilities
• Ultrafiltration capabilities
• 4 x Class 100,000 rooms that can be
retrofitted to Class 10,000
• 2 x 4,000 L reactors to perform chemical
modifications on isolated product
• Ability to perform conjugation chemistries
cGMP API Extractions
cGMP Manufacturing of Naturally Derived Products
• H.P. Acthar® bulk (API) – Questcor Pharmaceuticals, Inc.1
• Extraction of 9-DHB, 10-DAB and Paclitaxel
• Proprietary controlled substance API
1As
released publicly by joint press release on June 29, 2005 (released publicly by QuestCor)
API Process Scale Extractions
• 1 x 800 L Littleford DVT Polyphase extractor
• Extract, filter, and dry in same vessel
• Same utilities as a reactor
• 50, 27, and 5 sq. ft. evaporators
• 4000 L fractional still
• 2 x 400 L columns for silicas and
macroporous resins
• 400 L and 800 L 316L SS accessory reactors
cGMP API Purification
Column Sizes:
• Up to 400 L
Separation media experience:
• Normal phase silica
• Reverse phase silica
• Hydrophobic interaction
• Ion exchange media
Application of our expertise to both
natural products and synthetic
purifications
Animal Extraction Facility
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Facility designed for animal biomass extractions – API Injectables
4000 ft2 of total space
Refrigeration/freezer storage
Air-lock separation from primary processing and finishing suites
Extraction throughput up to 300 kg/biomass/day
Lyophilization (40 ft2 shelf space)
Flexible utilities for added equipment
Dedicated to single product processing
Technology Applications
42 years experience providing:
• Protein/peptide processing chemistries
• Plant and animal derived enzymes and
substrates
• Synthetically derived biochemicals
Expanding with product
marketing partnerships
Technology Applications
Taxane Extraction and Semi-Synthesis
• Docetaxel and paclitaxel synthesized from 10deacetylbaccatin III produced from a sustainable
natural resource
• In partnership with Taxolog Inc. of Fairfield, NJ
• Utilizing the IP of Dr. Robert Holton, et al. of Florida
State University
• Docetaxel - U.S. marketing partnership with Sandoz
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AcO
O
O
NH
H3C
CH3
CH3
CH3
O
OH
OH
Paclitaxel
(USP)
O
HO
CH3
CH3
O
O
CH3
H3C
CH3
O
H OAc
OBz
H3C
O
CH3
NH
CH3
CH3
O
OH
OH
Docetaxel
O
H OAc
OBz
Technology Applications
PEGylation of Large and Small Molecules
• Development of novel PEGylation technologies
• Developed unique PEG delivery solutions for
insoluble small molecule drugs
• Manufacturer of custom cGMP MPEG
derivatives tailored to your specifications
Our products are used by numerous biotech
companies for commercial projects
Vectra MPEG Derivatives
O
O
H3C O
CH 2 CH 2O
CH 2 CH 2
n
Vectra MPEG Propionaldehyde
10K, 20K, 30K
H3C O
H
CH 2 CH 2O
CH 2 CH 2
NH2
H3C O
CH 2 CH 2O
CH 2 CH 2
n
n
Vectra MPEG Amine
10K, 20K, 30K
Vectra MPEG Maleimide
10K, 20K, 30K
N
O
Innovative Technologies
BioVectra and Quanta BioDesign Announce Cooperation
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Quanta BioDesign develops and commercializes an extensive line of
proprietary low MW discrete polyethylene glycol (dPEG®) products.
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Quanta’s single MW dPEG® products can eliminate issues with
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aggregation
non-specific interactions
poor solubility
poor delivery
short half-life
toxicity
antigenicity
Expanding partnership provides our clients with low MW dPEG® and novel
linking chemistries for antibody drug conjugates.
Capital Expansions
During 2011-2013, BioVectra has 3 expansions completed or planned:
• New fermentation suite
• New synthetic drug substance wing
• New API production facility for a dedicated customer base
Capital Expansions
Fermentation
capacity is
doubled for
clinical
projects
Operations
will grow in
these
ways
Staff will grow
from 150-250
at project
completion
Synthetic
capacity is
quadrupled
Why BioVectra?
Long term
view as
strategic
supplier and
partner
Bridging
biotech and
classic
pharma
project needs
Proven experience
in specialized
technological
applications
Contact Information
BioVectra Inc.
11 Aviation Avenue
Charlottetown, PE
C1E 0A1
Tel:
Toll Free:
Fax:
www.biovectra.com
(902) 566-9116
(866) 883-2872
(902) 628-2045
[email protected]