Nordmark – Your Partner in Biological Drug Development and Production Welcome Benvenuto Bienvenue Bienvenido Willkommen bei Nordmark
Nordmark – Your Partner in Biological Drug Development and Production
Welcome Benvenuto Bienvenue Bienvenido
Willkommen bei Nordmark
Willkommen bei Nordmark
Nordmark – Family-owned Business with Long Tradition
Founded: > 1927
Headquartered in Uetersen: > near Hamburg, Germany
Solid revenue base: > EUR 90 m (2017)
Number of employees: > ~ 550
~ 40 long-standing international partners > in biotech and pharmaceutical industry
Fully integrated pharmaceutical company with proven track record
Nordmark at a Glance
> Leading service provider for development and manufacturing of biopharmaceutical APIs > Biological extracts > Non-recombinant proteins > Monoclonal antibodies (mAb) > Other recombinant proteins
> Entire value chain from development to marketed drugs
> Significant track record in process develop- ment and production
> State-of-the-art GMP-certified manufacturing facilities
> Highest standards in quality control
> Vast experience in international regulatory approval processes and programs
> Commercialization know-how based on own drugs
Tailor-made solutions to turn your innovation into marketed drugs
Nordmark Uetersen – Sufficient Room for Expansion
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| 1 Biocenter | 2 Administration | 3 Pharm. development | 4 Norbitec | 5 API production, Pancreatin, Extracts, Collagenase | 6 Quality control | 7 Process development (API) | 8 Pharm. production, Semi-solid drug forms | 9 Engineering and power station | 10 Analytical development | 11 Pharm. production, Solid drug forms | 12 Packaging | 13 Warehouse
1927Foundation Nordmark Werke
1928LaunchHepatrat
1930LaunchEnzynorm
1943Complete relocation to new manufacturingsite in Uetersen
1950Launch
Thrombophob
1969Launch
Panzynorm forte
1968Take-over by
BASF AG
1975BASF acquired
Knoll AG
1987Launch Panzytrat
(film-coated microtablet)
1993LaunchClivarin
2001MBO Nordmark
Independent
1996Launch Iruxol
2007Launch Silapo
and Collagenase NB11
2003Foundation
Norbitec2010Foun-
dationViprinex
2012Acquisition
BIBITEC
2015Launch Collage-
nase AF11
Nordmark History – More than 90 Years of Experience
Long tradition in biological APIs and finished drug products
1 Biochemical reagent, distributed exclusively via SERVA Electrophoresis GmbH until 2017
2018Take-over
biochemicals distribution
Nordmark – The Specialist for Biological APIs
Nordmark Development
Biologics from lab to market
Services> Process development> Cell line/strain development> Analytical development> Formulation, fill & finish> Regulatory support> Validation & GMP production
Areas of expertise> Extraction from biological materials> Microbial fermentation> Microbiome> Mammalian cell culture
Nordmark Biological APIs
Market leading manufacturer of biological APIs
Extraction from biological materials> Pancreatin> Pepsin> Tannin albuminate
Biotechnological production> Collagenase> Erythropoietin* (EPO)
Nordmark Pharma
Finished drug products based on biological APIs
Manufacturing of finished drug products for partners and Nordmark proprietary brands> Granulation and film-coating > Compression and encapsulation> Microtablets> Ointments and sterile ointments> Primary and secondary packaging
Nordmark Group
Combining development and manufacturing excellence with commercialization know-how
* Norbitec, JV with BIOCEUTICALS Arzneimittel AG 6
Nordmark Development – Biologics from Lab to Market
BIOTECH
Mammalian cell lines*/microbial strains> Screening and clone selection> Cell line and strain development> Manufacture of MCB/WCBs (GMP)> Scale-up and scale-down studies> Up- and down-stream processing> Process optimization> Virus studies
Processing techniques> Extraction> Purification> Filtration> Drying> Milling> Virus studies
From lab to production scale
EXTRACTS
* With partners
Nordmark Biological APIs – Market Leading Manufacturer of Biological APIs
FERMENTATION/CELL CULTURE
Microbial fermentation> Collagenase for wound debridement> Purified collagenase as biochemical for cell isolation (several grades)
CHO cell culture (Norbitec)> Erythropoietin for anaemia
Porcine origin> Pancreatin> Pepsin
Other origin> Tannin albuminate
BIOLOGICAL EXTRACTS
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Pancreatin> Capsules with pellets or microfilmtablets> Film-coated tablets
Collagenase> Ointment
Others> Sugar-coated tablets> Effervescent tablets
Nordmark Pharma – Finished Drug Products for Partners and Own Brand
FOR PARTNERS NORDMARK BRAND
Pancreatin> Pankreatan®
Heparin> Thrombophob®
Pepsin Ph. Eur. > Enzynorm® f
Fully Integrated Pharmaceutical Company
Nordmark provides the complete value chain to meet your drug development needs all the way through to commercialization
BIOPROCESS DEVELOPMENT(USP AND DSP)
GMP-COMPLIANTAPI PRODUCTION
FORMULATION FILL & FINISH
ANALYTICS AND QUALITY CONTROL
REGULATORY AFFAIRS
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Bioprocess Development – Upstream
* With partners
Strain Selection/Cell Line Development> Bacteria> Yeasts> CHO and others*> Hybridoma*
Genetic Engineering> Recombination> Codon usage> Mutagenesis
Expression Studies> Screening studies> Characterization> Clone selection> Research cell bank
Media Optimization> Screening studies> Multivariate (DoE) studies> Final host selection
Process Development> Multivariate (DoE) studies > Parallel bioreactor system> Up to 2 L scale (cell culture)> Up to 42 L scale (microbials)
MCB and WCB> cGMP conditions> Qualified and monitored storage
Scale Up> Up to 200 L scale (cell culture)> Up to 500 L scale (microbials)> Process adaptation
Process Transfer> In-house engineering> Process setup
Production at Pilot Scale> Up to 500 L> Clinical supply> cGMP conditions
Commercial Production> Supported production > cGMP conditions
Bioprocess Development – Downstream
Cell Removal> Filtration> Centrifugation
Purification> Development of purification and filtration steps> Process optimization > Evaluation of process robustness and reproducibility (Design Space)> Optimization of storage conditions
Analytical Development (IPKs)> Activity-assays> Aggregates (SEC)> Identity and purity (SDS-PAGE; HPLC/UPLC) > HCPs (ELISA); DNA (qPCR)> Protein A/L, leachables> Isoforms (CE)> Protein concentration (UV-Assay)
Virus Reduction> Nanofiltration> Chromatography> Physical treatment> Virus validation studies
Production: Pilot Scale> ÄKTA pilot systems> Bioprocess systems> Clinical trial supply> cGMP conditions
Scale Up> Up to 100 L batch scale> Process adaptation
Process Transfer> In-house engineering> Process setup> Process optimization> Trainings> Production support
Production: Full Scale> Up to > 1000 L scale> Market supply> cGMP conditions
cGMP SERVICES
Process development and validation for Biological APIs originating from:> Animal organs and fluids (e.g. snake venom)> Bacteria and yeasts (recombinant and non recombinant)> Mammalian cell cultures (mAbs and other recombinant proteins)
For clinical up to commercial supply
Certified cGMP Production
Tailor-made solutions to turn your innovation into marketed drugs
Clinical trial manufacturing> Stainless steel stirred bioreactors> Single use bioreactors
Commercial manufacturing> Stainless steel stirred bioreactors> Industrial chromatography systems> Lyophilization
cGMP PRODUCTION FACILITIES
Pharmaceutical Development
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Photo: © PAMASPhoto: © Bruker
Formulation Development> Protein-based liquid, semi- solid and solid formulations> Live biotherapeutic (micobiota) based formulations> DoE based studies
Primary packaging development
Scale up and technology transfer
Subvisible Particles in Solutions via Dynamic Light Scattering (DLS) > Particle size distribution in nm-range> Detection of soluble protein aggregatesSubvisible Particles in Solutions via Light Obscuration (LO)> Particle count in µm-range> Detection of insoluble protein aggregates> Pharmacopoeial method
Protein UnfoldingTemperature (Tm) via µDSC> High-trough-put screening of liquid formulations> High-trough-put prediction of storage stabilityProtein Secondary Structure via FT-IR (ATR)> Evaluation of liquid and solid formulations> Determination of changes in protein structure
DEVELOPMENT PROTEIN STRUCTURE PROTEIN AGGREGATION
Photo: © Wyatt Technology CorpPhoto: © TA Instruments
Solids> Granulation and film-coating> Compression and encapsulation> Micro-tablets
Semi-solids> Ointments and sterile ointments
Liquids> Oral and parenteral*
Manufacture of Clinical and Commercial Supplies
Solids> Bottles and blisters
Semi-solids> Sterile and standard tube
Liquids> Oral and parenteral*> Glass & blow-fill-seal vials*
Secondary packaging> Art works, cartons and PLI> Commercial and clinical trial medication
* With partners
MANUFACTURE FILL & FINISH
Characterization and method development> Biological activity assays> Cell culture based assays> ELISA> Glycostructure analysis> Mass spectrometry> Chromatography (TLC/HPLC/UPLC/GC)> GLP-compliant studies
Cutting Edge Analytics and Quality Control
According to international guidelines > ICH (Int’l Conference on Harmonization of technical requirements for registration of pharmaceuticals for human use)> EMA (Europ. Medicines Agency)> WHO (World Health Organization)
In-process control> Expression system> Fermentation
Release testing according to USP and Ph. Eur.> Protein identification, purity and content
Adventitious agents> Viral safety, impurities
Nordmark’s cutting-edge analytics guarantee consistently high quality of your products
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PROTEIN ANALY TICS QUALIT Y CONTROL STABILIT Y TESTING
Wealth of Regulatory Experience
Based on our experience we can contribute to your success in drug product development
> Preparation of registration documentation
> Support of registration processes (worldwide)
> Regulatory consulting services from early development to registration
> Strategic advice
> Project management
> Lifecycle management/maintenance for existing products
Customer support through all stages of approval process up to registration
BfArM Health Canada
KFDAJMHLW
FDAMEB
LaSD Schleswig Holstein
EMAANVISA
MPA Ministerio da Saude
Proven Expertise in Bioprocess Development
Track record, selected projects:
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Partner Timeline Projekt Product Process
advanceCor 2011-2014 Process development, GMP-production of preclinical and clinical material PH I
Recombinant fusion protein
CHO cell line
Ticeba 2013 Purification process development, GMP production Monoclonal antibody
Hybridoma technology
Greenovation 2015/16 Technology transfer, GMP production of clinical material PH I
Enzyme Moss cultivation (P. patens)
MATHIASConsortium
2017 Process development, GMP production Monoclonal antibody
CHO cell line
HelmholtzZentrum
2017/18 Process development, GMP-production of preclinical and clinical material PH I
Fab antibody fragment
CHO cell line
US partner ongoing Microbiome Live Biothera-peutic Product
Microbials
Nordmarkproprietary
ongoing Process development, GMP production, formulation, pri-mary packaging development
Several non- recombinant proteins
Microbial fermentation
Nordmarkproprietary
ongoing Process development, GMP production, formulation, pri-mary packaging development
Ancrod, non- recombinant protein
Extraction from snake venom
Successful Project Development & Technology Transfer
With our expertise we bring products to market
Process development clinical Phase III
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
Example: Industrial manufacturing of Erythropoietin (EPOzeta)
Establishment of new production site
EMEA approval EPOzeta
Process development industrial scale
Market supply EU (Silapo®, Retacrit®, EPOBEL®)
Start of approval process USA (Hospira)
Joint Venture with BIOCEUTICALS Arzneimittel AG
New Biological APIs under Development
Structure determined in cooperation with DESY*
* X-ray analysis by Deutsches Elektronen-Synchrotron DESY, Hamburg, Germany ** Exocrine Pancreatic Insufficiency 20
Ancrod is ... ... a highly active fibrinogenase isolated from venom of malayan pit viper bred in Nordmark‘s own snake farmAncrod can ... ... favorably influence blood viscosityAncrod has successfully passed ... ... extensive preclinical tests ... clinical studies PH I ... and is currently in PH II
ANCROD BURLULIPASE COLLAGENASE
Burlulipase is ... ... a pure, liquid, animal- and virus-free, highly active, acid stable lipase-only product from bacterial fermentation with a favorable safety profileBurlulipase can ... ... effectively improve fat absorption in EPI** patientsBurlulipase has successfully passed ... ... extensive preclinical tests ... clinical studies PH I and IIa (PoC)
Collagenase is ... ... an enzyme obtained from fermen- tation with Clostridium histolyticumCollagenase is used for tissue dissociation... ... e.g. in wound healing, edema- tous fibrosclerotic panniculopathy (cellulite), Dupuytren‘s contracture and tissue-engineeringCollagenase development by Nordmark: ... animal-free collagenase
Worldwide Business Relationships
Partnering with Nordmark is about achieving your goals. Together!
Partner References
Our long-term relationships demonstrate the satisfaction and trust of our partners
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Nordmark Arzneimittel GmbH & Co. KG [email protected]+49-(0)4122 712-0www.nordmark-pharma.de
[email protected] +49-(0)4122 712-907 www.nordmark-biotech.de
Nordmark – Your Partner of Choice
Keys to our success are competence, quality,
responsibility and reliable long-term relationships
> Leading manufacturer of high quality biological APIs based on more than 90 years of experience
> Proven track record in development and manufacturing
> Family-owned business in which your projects are handled as if they were ours
> Extensive regulatory experience adds significant value for our partners
> Strong commitment to long-term partnerships built on trust, reliability and execution
> Fast and simple decision-making processes
> Open to various collaboration models
> Drug product development and manufacture from scratch to batch and beyond
> Whatever size your project – your success is our priority
Contacts