From chemical development to high value products 06/2018 1 OUR - - PowerPoint PPT Presentation

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OUR SCIENCE, YOUR PRODUCT

06/2018

From chemical development to high value products

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OUR SCIENCE, YOUR PRODUCT

What we do

Custom design and production of specialty chemicals, intermediates and APIs

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OUR SCIENCE, YOUR PRODUCT

Who we are

A Swiss chemical company founded in the thriving business environment of Zurich in 2001. We have since grown to a global provider with a portfolio of 2500 products, which we deliver to over 20 European countries, all over the Americas and Asia.

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OUR SCIENCE, YOUR PRODUCT

Why choose us

We combine Swiss excellence with high-end European R&D expertise and low development and production costs. We use intellectual property strategically, which gives us greater corporate flexibility and increased market value of our products. We are trusted by the world’s leading chemical and pharmaceutical companies.

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OUR SCIENCE, YOUR PRODUCT

Our approach

We apply cost-performance benchmarks on a project-by- project basis to find the best solution for our customers’ project. We are proactive and anticipate any regulatory bottlenecks with a view to mitigate business risks and reduce time-to-market. We use all our resources to design and implement innovative processes to produce your product sustainably and ensure uninterrupted supply for your business.

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OUR SCIENCE, YOUR PRODUCT

Global presence

VIO Chemicals AG – HQ Zurich, Switzerland R&D Centre Thessaloniki, Greece China Representative Office Nanjing, China Manufacturing site (VIO Organic Chemicals Co. Ltd. /Yangcheng HaoHua) Binhai, China Sales Offices & Agents in North America France Spain Japan

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OUR SCIENCE, YOUR PRODUCT

Our facilities – The R&D centre

A powerhouse of science at highly competitive rates

• A team of 35 highly experienced scientists

and professionals

• Primary focus on innovative, non-patent

infringing, safe and robust processes

• Over 150 publications in prime journals

with average impact factor >4

• More than 30 patent filings

OS: 7 PhD, 6 MSc AD: 3 PhD, 5 MSc, 1 BSc QA/RA: 1 PhD, 2 MSc IP/ScA: 2 PhD, 1 MSc

Organic Synthesis IP Scientific Affairs QA/RA Analytical Development

+ Management: 1 PhD / 1 MSc

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OUR SCIENCE, YOUR PRODUCT

8x Fume Hoods 4x Rotary evaporators 1x Flow chemistry system 1x Gas reaction module Ozonolysis equipment Vacuum Pumps Drying & vacuum ovens

Organic synthesis lab

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OUR SCIENCE, YOUR PRODUCT

2x 50L Reactors (-45 to 150°C) 1x 30L Reactor (-35 to 150°C) 1x 20L Reactor (-40 to 150°C) 1x 5L Reactor (-30 to 150°C) 1, 2 and 5L High Pressure Reactors Nutsche filter, Centrifuge 20L Rotary Evaporator

Kilo lab

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OUR SCIENCE, YOUR PRODUCT

7x HPLCs (Shimadzu), with UV, PDA, RI, ELS, FR detector options 1x Preparative HPLC (Shimadzu) 1x LCMS (Shimadzu) 1x FTIR (Perkin Elmer) 2x GC (Shimadzu) 1x Digital Polarimeter (Perkin Elmer) Stability Chambers (short/long term) Photostability Chamber

Analytical development labs

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OUR SCIENCE, YOUR PRODUCT

Our facilities - The manufacturing site

Reliable, flexible, cost-efficient and prompt manufacturing services

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OUR SCIENCE, YOUR PRODUCT

State-of-the-art production assets

• VIO Organic Chemicals Co. Ltd, registered in China as Yangcheng HaoHua
• More than 4,500 m² of manufacturing space in a total plot area of 27,000 m²
• Three production units, one cGMP standard
• High flexibility in production capacity, with volume ranging from grams to metric tons
• Clean room for the production of intermediates, ISO Class 8
• Multi-purpose and single product plants with medium to high throughput
• Glass-lined and stainless steel reactors from 500L to 5,000L
• Broad range of technologies and types of chemical reactions
• Specialization in enzymatic processes for chiral products
• Close collaboration with an enzyme developing company
• Waste management system for solid, gas and water according to local regulations
• Water purification system
• Solvent recycling technology
• Strict compliance with local health, safety and environmental policies and regulation
• ISO 9001 certification for Quality Management System
• Continuously aiming for green chemistry.

Our facilities - The manufacturing site

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OUR SCIENCE, YOUR PRODUCT

Our services

• R&D
• Manufacturing
• Strategic sourcing
• Integrated support

and consultancy in QA, IP and RA

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OUR SCIENCE, YOUR PRODUCT

R&D and manufacturing

High-value, cost-competitive and non-infringing solutions

Process R&D We optimise or re-design the chemical process to arrive at your exact product. Our goal is to improve yields and the overall quality of your product and minimise production costs. Analytical research, development and validation We undertake full characterisation analysis to ensure the highest quality for the properties

• f your product.

Technology transfer and production We develop chemical transformations to safe, robust, scalable and exactly repeatable manufacturing processes.

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OUR SCIENCE, YOUR PRODUCT

R&D and manufacturing

Our approach for high-value products

Technology Transfer Research & Development Evaluation & Design Inquiry Scale-up Manufacturing

• Innovative and efficient processes
• Overcome key constraints
• Overcome patent protection
• Wide range of technologies
• Cost-effective solutions
• Sustainable processes

From Europe to China

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OUR SCIENCE, YOUR PRODUCT

best process novel process existing tech IP landscape process development analytical development supply chain QA/IP support Regulatory/LCM support implementation and scale up CM evaluation and assignment QA monitoring and support quality control process control IP generation and clearance

Stage Gate Project Management System The R&D centre:

• is certified according to ISO 9001 & ISO 14001 since 2006, with the scope of “Research and

development of Active Pharmaceutical Ingredients”.

• functions within an integral Stage-Gate Project Management System, which implements and updates

an established Quality Management System, with written Standard Operating Procedures. That way we can ensure traceability throughout the developing process by following basic GMP documentation requirements. The work performed in the lab involves process and analytical development, including proper IP support, and delivers a full technical package for technology transfer to the manufacturing unit, backed with quality assurance and regulatory insight and support for commercialization.

Technology Transfer Research & Development Evaluation & Design Inquiry Scale-up Manufacturing Stage Gate Project Management System

How we do it

ISO 9001 & 14001 certification and GMP-compliant quality system

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OUR SCIENCE, YOUR PRODUCT

Tech-transfer & Scale-up

SG6: Technology Transfer

• Key Raw Material suppliers approval
• Manufacturer quality status and

technical evaluation and assignment

• Manufacturing technology transfer
• Analytical method transfer
• Lab familiarization and process

implementation troubleshooting SG7: Scale-up manufacturing

• Process scale-up/ piloting and

commercial production

• Commercial production
• troubleshooting
• Commercial cost calculation
• QA and RA support for registration

and lifecycle management

Scale-up material

Evaluation & Design

SG1: Project framing

• Inquiry elucidation/ Market intelligence
• Goal framing and project outlook
• Target selection/acknowledgment
• Prior art, IP landscape and

existing technology evaluation

• Identification and evaluation of

constraints

• Potential involvement strategies

SG2: Project evaluation and design

• Novel approach ideation vs prior art
• New technologies potential
• Shadow cost benchmarking and

competition evaluation

• Targeted properties and specifications
• Targeted quantities and timelines

Best Approach Proposals

Research & Development

SG3: Feasibility

• Proof-of-Concept and Feasibility studies
• IP generation and Optimal ROS

selection SG4: Optimization

• Assessment/preparation of impurities

Lab samples and Reference Standards

• Analytical method development
• Intermediates and product

specifications

• Pre-stability/ holding time studies

SG5: Lab Validation

• Analytical Method validation/protocols
• Raw Material Cost calculation
• Technology Transfer Document
• Full Technical Package

R&D Process for Scale-up Customer involvement throughout the whole process Quality System - Project Management System

Stages-Gates Workflow

ISO 9001 & 14001 certification and GMP-compliant quality system

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OUR SCIENCE, YOUR PRODUCT

R&D carbohydrates expertise

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OUR SCIENCE, YOUR PRODUCT

R&D carbohydrates expertise highlights

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OUR SCIENCE, YOUR PRODUCT

R&D two main methodologies to access key synthons

Intramolecular cyclization

Starting from carbohydrates Starting from renewable sources e.g. pyruvates carbasugars, cyclopentyl- carbocyclics 1,3-aminoalcohols, carbocyclic nucleosides polyhydroxylate d carbocyclics non-natural α-aminoacids

Hetero Diels-Alder Intramolecu lar cyclization

γ-aminoacids

α-substituted γ-aminoacids

Intramolecular cyclization

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OUR SCIENCE, YOUR PRODUCT

Basic Patent

• 7+1 chemical steps
• diazonium salt intermediate
• cyanide anion attack

2nd generation prior art processes

• oxime dehydration
• HCOOH reflux >5h @100-110oC
• ur process: WO 2015/018507
• trivial catalyst, renewable terminal oxidant
• cyanide-free process
• atom economy, green reagents
• successfully scaled up to commercial level

Selected Examples: API development

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OUR SCIENCE, YOUR PRODUCT

• ur approach: PCT/EP2016/001053
• novel, selective N-methylation chemistry
• feasibility stage successful (SG3), optimization pending (SG4)
• available and cheap reagents
• streamlined chemical steps, telescoped synthesis

2nd generation prior art processes

• strict conditions to avoid O-methylation by-products
• available but expensive methylation reagent
• isolation and purification of intermediates required

Selected Examples: Intermediate/API development

• advantageous transient protection technology
• validated competitive API process ready to scale-up (SG5)

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OUR SCIENCE, YOUR PRODUCT

Manufacturing

Enzyme catalyzed synthesis of Nebivolol intermediates

1. Formation of acetic ester 2. Lipase catalyzed selective ester cleavage of one enantiomer 3. Separation 4. Soapification of second enantiomer Ketoreductase catalyzed selective reduction Ketoreductase catalyzed selective reduction

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OUR SCIENCE, YOUR PRODUCT

Selected Examples: Latest projects

Key scaffolds and intermediates Carbohydrates Bile acid derivatives and conjugates

• optimal ROS design and selection from platform raw materials
• focus on reaction mechanisms to identify critical transformation triggers
• critical process parameters to control key quality attributes
• smart downstream processing towards flexible product specifications
• robust, scalable and high-throughput manufacturing processes
• lean industrial operations for low production costs
• ptimal selection, sourcing and quality control of raw materials

for low cost and high reliability supply chain

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OUR SCIENCE, YOUR PRODUCT

Manufacturing example

Bicyclo[1.1.1]pentanes

• Novel chemical tools for

bioisosteric replacement of aromatic and lipophilic groups

• Mimicking the para

substitution pattern on arenes

• r
• Serve as surrogates for tert-

butyl/lipophilic moieties

• Patent circumvention

Bio ioiso isoste teri ric swit itch

• r
• r

Bioisosteric switch

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OUR SCIENCE, YOUR PRODUCT

Our products

• APIs
• Intermediates for API synthesis
• Drug formulation excipients
• High-quality amino acid derivatives

for peptide synthesis (99.5% purity)

• Bicyclo[1.1.1]pentanes
• Chiral scaffolds and building blocks
• Specialty chemicals and reagents
• Organophosphorous products
• Plant ingredients as nutritional

supplements Supplying the pharmaceutical industry and beyond

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OUR SCIENCE, YOUR PRODUCT

Products

Our approach for new products

Step 1: Conduct market evaluation Step 2: Define product specifications Step 3: Evaluate to right production partner in China Step 4: Consult improvements with partner on how to meet specifications

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OUR SCIENCE, YOUR PRODUCT

Products example

Low Endotoxin Trehalose (USP/NF, EP, JP) Excipient for biopharmaceuticals

• Technical name: α,α,-D-Trehalose dihydrate
• CAS No: 6138-23-4
• Empirical formula: C12H22O11.2H2O
• Molecular weight: 342.3 + 36.0

TEST SPECIFICATION Identification IR: Corresponds to CRS spectrum Appearance White to almost white, crystalline powder Specific optical rotation [α]D

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+197° to +201° (10%W/V in H2O) Purity (HPLC)

• min. 99.0%

Impurity A (HPLC): (+)-D-Glucopyranose (Glucose)

• max. 0.5%

Impurity B (HPLC): Oligosaccharides

• max. 0.5%

Each unspecified Impurity

• max. 0.2%

Total impurities

• max. 1.0%

Water content (KF) 9.0% -11.0% Sulphated ash

• max. 0.1%

Chlorides

• max. 125 ppm

Sulfates

• max. 200 ppm

Heavy metals (Ph. Eur.)

• max. 5.0 ppm

Lead (Pb)

• max. 1.0 ppm

Arsenic (As)

• max. 0.5 ppm (XRF)

Iron (Fe)

• max. 3.0 ppm (Ph. Eur.)

Copper (Cu)

• max. 3.0 ppm (XRF)

Mercury (Hg)

• max. 0.1 ppm (XRF or AAS)

Total nitrogen

• max. 0.005%

Soluble starch negative in 1 g Fehling test

• max. 0.1% Cu2O

pH 4.5 to 6.5 (10%w/v in H2O) Residual solvent Ethanol max. 5000 ppm Bioburden Total viable counts: 100 CFU/g Yeast: max. 10 CFU/g Staphylococcus aureus, Salmonella, E. coli and Pseudomonas aeruginosa: negative in 1g Endotoxins

• max. 2.5 IU/g

Storage conditions 15°C to 25°C Shelf life 2 years from date of manufacture

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OUR SCIENCE, YOUR PRODUCT

Products example

Sodium stearyl fumarate (USP/NF, EP, JP) Used as an excipient/ lubricant

• Technical name: Sodium stearyl fumarate
• CAS No: 4070-80-8
• Empirical formula: C22H39NaO4
• Molecular weight: 390.53

TEST SPECIFICATION

Identification IR has to confirm with CRM Appearance White or almost white fine powder Solubility Practically insoluble in water and acetone, slightly soluble in methanol, practically insoluble in acetone and anhydrous ethanol Assay 99.0-101.5% Water content

• max. 5.0 %

Saponification value 142.2-146.0 Heavy metals

• max. 20 ppm

Lead

• max. 10 ppm

Arsenic

• max. 2.0 ppm

Related substances Largest single impurity max. 0.5% Total impurities max 5.0% Sodium stearyl maleate

• max. 0.25 %

Stearyl alcohol

• max. 0.5 %

Particle size distribution Can be adjusted within certain limits, such as: D10: max. 2.5µm D50: max. 10 µm D90: max. 30 µm

Explore complete product list

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OUR SCIENCE, YOUR PRODUCT

Strategic sourcing solutions

Securing an uninterrupted supply for your business

• Over 15 years of presence in the Chinese

market with a local ISO 9001-certified

• ffice in Nanjing and a strong procurement

team of 8 people

• Market knowledge and price benchmark
• Excellent knowledge of local regulations
• Supplier screening, evaluation and risk

assessment

• HSE evaluation, GMP and QA monitoring
• Complete logistics services
• High quality, reliable supply, competitive

pricing, regulatory compliance and fast delivery of your product

• Complementary consulting and regulatory

services

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OUR SCIENCE, YOUR PRODUCT

Integrated support and consultancy in QA, IP & RA

Holistic approach to ensure marketability of your product

• Total QA support throughout all stages of

synthesis, analysis, setting of specifications and monitoring of results in compliance with ICH guidelines, while providing full traceability during the process development, analysis and stability studies.

• Integrated or independent IP technical and

legal support to ensure non-infringing processes.

• Proactive strategic RA insight and scientific

advice from the early stages of development and assessment period up to final approval of the DMF and product lifecycle management.

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OUR SCIENCE, YOUR PRODUCT

For inquiries, contact us at info@viochem.com

Watch our corporate video “Our science, your product”

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OUR SCIENCE, YOUR PRODUCT

VIO IO CHEMICALS AG Dufourstrasse 107 CH-8008 Zurich Switzerland +41 44 380 24 44 info@viochem.com

DISCOVER VIO www.viochemicals.com CONNECT WITH US @VIOChemicals /VIO Chemicals