INNOVATION
FROM TRADITION
CUSTOM SYNTHESIS
Services & Capabilities
CORE CHEMISTRIES
AND TECHNOLOGIES
CHEMISTRIES
> Asymmetric Processes
> Biotransformations
> Organometallic Chemistry (Continuous Flow and
Turbo-Grignard, Pd/Zn/Li Coupling reactions, Reductive
Amination)
> Metal Hydride Reductions
> Hydrogenation - Conventional Hydrogen Donors &
Asymmetric Hydrogenation (Noyori HTC)
> Nitrogen and Oxygen Methylation and Demethylation
> Amino Acids Protection and Derivatization
> Hofmann Rearrangement and Elimination
> Mannich Reactions
> Diels-Alder and Hetero Diels-Alder Reactions
> Cycloaddition processes - Sigmatropic and Thermal
Rearrangements (Claisen)
> Safe and Innovative Cyclopropanation processes
> Cyanation (with alkali metal cyanides and substitutes)
> Catalytic Nitric acid-free Nitration
> Oxidative Transformations at Carbon, Nitrogen and
Sulfur atoms
> Diazotization
> Ozonolysis (Continuous flow)
> Chiral Epoxides Chemistry (synthesis and processing)
> Sulfur and Oxidised Sulfur Compounds (synthesis and
processing)
> Heterocyclic Compounds (synthesis and processing)
TECHNOLOGIES AVAILABLE
> Cryogenic chemistry (-80°C)
> Freeze/Spray Drying
> High temperature (+250°C)
> Column Chromatography (Conventional and Ion Exchange)
> Enantiomers and Diastereoisomer Separations (Classical
and Dynamic-Induced Resolutions, Hydrolytic Kinetic
Resolution)
> Crystallization Engineering – Large Scale Reactive
Crystallization, Spherical Agglomeration, Handling metastable polymorphs
> Wiped film evaporation
> Separation/Purifications using Membrane Technologies
THE COMBINATION OF OUR PROFOUND CHEMICAL KNOW-HOW
AND THE WIDE RANGE OF CAPACITIES MAKES US A STRONG
PROVIDER FOR YOUR PRODUCTS
R&D
> Development of Highly Complex Processes from Route
Discovery to Large Scale Synthesis
> Scale-up of Robust Processes
> Process Safety Studies (multiple Reaction Calorimetry
techniques)
> Design and Development of new Routes of Synthesis and
implementation of new synthetic methodologies for 2nd
Generation Processes
> Expertise in Process Optimization
> Troubleshooting externally-developed processes by scaledown
> Designing long-term, cost-effective processes for APIs and
Intermediates
> Technology Transfer - in/out
> Process Analytical technology (PAT) In-situ IR, In-situ Raman,
Lasentec
> Continuous flow Processes
> Micro technologies
> Handling High Potency APIs
> Biocatalysis
API FINISHING
CAPABILITIES
> Filter Dryers
> Fluid Bed Dryers
> Tumble Dryers
> Turbo Dryers
> Tray Dryers
> Milling
> Blending
> Micronization
SPRAY DRYING & BULK LYOPHILISATION (Avrillé)
Combined with Nanofiltration and Ultrafiltration
> Freeze Drying bulk
> Spray Drying bulk
> Ultra Filtration
> Nano Filtration
ANALYTICAL CAPABILITIES
AND QUALITY CONTROL
> In-house development of new analytical methods
> Validation and transfer of analytical methods
CHEMICAL AND
INSTRUMENTAL ANALYSIS
> HPLC, UPLC, GC, Headspace-GC
> IR, UV, NIR, Raman
> GC-HRMS, GC-MS
> HPLC-MS, HPLC-TOF-MS
> NMR (400 MHz)
> Ion chromatography
> DSC
PHYSICAL & POLYMORPHS ANALYSIS
> Wet and dry PSD analysis (laser)
> BET surface area analysis
> Polarimetry, Refractive index measurement
> Densimetry, Powder colorimetry
> Turbidimetry
High Resolution X-Ray Powder Diffraction for Detecting
Polymorph Contamination using Synchrotron Radiation
Conventional X-Ray Powder Diffraction
CUSTOMER
SATISFACTION
IS OUR KEY DRIVER
SERVICES
> Supply Chain Management & Procurement
> Warehousing
> Logistics & Transportation
> Reach Registrations
> Regulatory Filings (DMF, CTD, Ceps) Worldwide
> Intellectual Property Assessments
> Legal Support
FACT
SHEET
>Long tradition in process development & API / intermediates manufacturing
>2 Facilities:
- Lonigo, Italy, Site built in 1975, FDA inspected
- Avrillé, France, Site built in 1972, FDA inspected
>Each facility equipped with:
-Process Development labs, Process Safety labs, Solid State Investigation labs, cGMP kilolab, cGMP pilot plant,
Industrial plant, Analytical labs, Waste treatment
-Very flexible equipment configuration and plant set up adapted to each product
-Ability to handle complex chemistry
-Capturing new emerging technologies
-Focus on Health, Safety & Environment
-Global QA Compliance
CAPACITY / REACTORS
LONIGO/ITALY
AVRILLÉ/FRANCE
TOTAL REACTOR CAPACITY
741 m
100 m3
PRODUCTION OUTPUT
2500 MT/year
215 MT/year
REACTION TRAINS
97
31
REACTORS: STAINLESS STEEL,
GLASSLINED & HASTELLOY
164
34
REACTOR RANGE: KILOLAB
10 - 25 L
15 - 30 L
REACTOR RANGE: PILOT
100 - 1200 L
50 - 1000 L
REACTOR RANGE: INDUSTRIAL
1000 - 17000 L
1000 - 10000 L
3
REGULATORY & GLOBAL COMPLIANCE
NUMBER OF DMFs WORLDWIDE: MORE THAN 300 (GLOBALLY)
CEPs, COS
CLASS OF PRODUCTS AUTHORIZED:
> APIs requiring multipurpose plant (i.e. Antiflammatories, Cardiovasculars, Antiepileptics, Antiparkinsons, etc)
> Antibiotics (excluded betalactams and cephalosporins)
SPECIFIC PRODUCT CLASSES THAT CANNOT BE HANDLED IN MULTIPURPOSE PLANTS:
> Antibacterials (non betalactam, non cephalosporins)
> Non Steroid Hormones (OEL µg/m3; OEB 4)
> Corticosteroids
EXCIPIENTS: CHEMICAL MODIFICATION, SPRAY DRYING & LYOPHILISATION
LONIGO/ITALY
AVRILLÉ/FRANCE
FDA INSPECTIONS
From 1986
From 1984
LAST INSPECTION
February 2013 EIR (04/30/2013)
December 2010 NO FORM 483
OTHER INSPECTIONS
AIFA - PMDA - KOREAN FDA
ANSM - PMDA - KOREAN FDA
COMPLIANCE
CERTIFICATES
ISO 14001
OHSAS 18001
ISO 14001
ELEMENTS
OF CUSTOM
SYNTHESIS
PROJECT
> NCEs from phase I to launch and commercial production
>Non cGMP intermediates
>cGMP intermediates / Regulatory Starting Materials
a)Synthesis route selection
b)Process Development
c)Technology transfer Customer-Zach
d)Technology transfer for raw and starting material process
to suppliers (Supply Chain Management)
>Mature APIs:
a)Technology Transfer to Zach
b)Site Transfer
c)Second Generation Processes: route finding, process
development, scale-up, cost management
PRODUCT
LIFECYCLE SERVICES
CGMP SMALL
QUANTITIES
CGMP PILOT
BATCHES
CGMP
PRE-INDUSTRIAL
PHASE I
PHASE II
PHASE III
> RoS selection
> Familiarization (PoC)
> Process development
> Analytical development
> Safety assessment
> RM scouting
> Development Report
> Scale up
> Process development
> Analytical development
> Safety assessment
> RM assessment
> Stability
> Development report
> IMPD
> REACH
> Scale up
> Process Development
> Analytical development
> Safety assessment
> Supply chain definition
> Stability
> Development report
> IMPD
> REACH
REGISTRATION /
VALIDATION
BATCHES
COMMERCIAL
BATCHES
REGISTRATION
LAUNCH
> Scale up
> Process Validation
> Analytical Validation
> Supply chain qualification
> Stability
> Campaign Report
> DMF / CTD
> REACH
> Productivity initiatives
(solvent recovery, yield
increase, etc.)
> Supply chain enhancement
> Quality Annual Review
> Stability
> DMF / CTD regular updating
> Second generation process
COMMERCIAL
PROJECT
MANAGEMENT
CUSTOMER
SATISFACTION
COMMERCIAL PRODUCTION
LAUNCH PRODUCTION
REGULATORY FILINGS –
DMFS, CTDS, CMC
REGISTRATION/
VALIDATION BATCHES
SCALE-UP
(ENGINEERING BATCH)
DEDICATED
PROJECT
TEAMS AND
PROJECT
MANAGERS
TAKE CARE
OF EVERY
ASPECT
OF YOUR
PRODUCT
PROCESS DEVELOPMENT FOCUS ON SCALABLE,
COST-EFFECTIVE,
ROBUST SYNTHESIS
PROCESS
FAMILIARIZATION
CONTRACTING
AND KICK-OFF
PROJECT PROPOSAL –
FOCUS ON OUR EXPERIENCE
AND TECHNOLOGIES
PROJECT
EVALUATION
CONFIDENTIALITY
AGREEMENT
BUSINESS DEVELOPMENT CUSTOM SYNTHESIS CONTACTS
ELENA KOLAXIDIS
Business Development Custom Synthesis
North America
Mobile +39 3482915372
[email protected]
NICOLAS GIRARD
Business Development Custom Synthesis
Europe and Japan
Mobile +336 76 06 52 10
[email protected]
Please contact us through our Commercial Offices (see below) or via our web site www.zachsystem.com
Zach System S.p.A.
Headquarter
Administrative Offices
Commercial Offices
Via Lillo del Duca, 10
20091 Bresso (MI) – Italy
Telephone +39 02 665241
Fax +39 02 66524979
www.zachsystem.com