Webcast Flow Chemistry Technologies: Market Status & Perspectives Le Quartz 75 cours Emile Zola 69100 LYON Villeurbanne Tel: +33 472 83 01 80 Fax: +33 472 83 01 83 Web: www.yole.fr Oct. 11, 2012 Flow Chemistry Technologies: Market status & perspectives - Webcast October 2012 Copyrights Yole Développement SA. All rights reserved.
Agenda Introduction Market Data and Forecasts Overview of the Applications Market Segmentation Company and Products Examples Current Market Status and Perspectives Conditions for Sustainable Growth Conclusions 2011 2
Introduction 2011 3
Flow Chemistry and MRT Definition Flow chemistry refers to the use of continuous flow reactors for chemical synthesis and process intensification, the opposite of batch chemistry. Flow chemistry uses Micro Reaction Technology (MRT), which refers to the miniaturized and micro fabricated components for mixing, separating, heating up, cooling down MRTisadisruptive innovative technology, totally changing the method of working and the way of thinking about chemistry. Main Users: Fine chemical industry and Pharmaceutical companies. MRT modules MRT system MRT production 2011 4
MRT Module Definition MRT Modules: Basic parts such as the microreactor, micromixer, micro heat exchanger, microseparation unit ready for connection. Applications: Individual MRT modules dedicated for R&D Commercially available modules to be assembled by the end user and to be connected together and with related equipment to obtain a production line. MRT for integration into an R&D system MRT for integration into an MRT plant for production 2011 5
MRT R&D System Definition MRT R&D System: MRT modules assembled and connected together with pumps, managed by software, creating a standalone system as one production line. Labtrix, Chemtrix (Nl) AFRICA Systems, Syrris (Uk) MMRS Ehrfeld BTS (De) Characteristic: ready to use system, fully integrated and automated for laboratory use 2011 6
MRT Plant Definition MRT Plant: MRT systems integrated in existing manufacturing plants or as a stand alone production unit. Micromixer integrated in a running plant, MicroInnova (At) ART PR49, Alfa Laval (Sw) Microplant for production, FzK (De), DSM (At) 2011 7
Market Data and Forecasts 2011 8
Our Vision of the Market R&D system market MRT modules in R&D system Module market Individual MRT modules for R&D Production system market MRT modules in MRT plant All the market data presented today are in Euros 2011 9
Module Market: Annual Demand in M (In M ) 14 Module Market: annual demand in M 12 10 8 6 4 2 0 Time MRT individual modules for R&D (M ) MRT modules for production (M ) MRT modules in R&D systems (M ) The global module market will reach 13.4M in 2017. 2011 10
R&D System Market: Annual Demand in M M/year 20 18 16 14 12 10 8 6 4 2 0 R&D System Market data and forecasts: annual demand in M$ Time System for R&D (M ) The systems dedicated to R&D market will sharply increase in order to reach 17.8M/year in 2017. 2011 11
Systems for Production: Annual Demand in M 25 System for Production (M ) 20 15 10 5 0 The systems dedicated to the production market will sharply increase in order to reach 23M/year in 2017. 2011 12
Cumulative Installed Based MRT Systems Units 300 250 Cumulative Installed based MRT Systems for Production 200 150 100 50 0 Time 2011 13
Conclusion: Market Data Trends ( M/year) 25 20 15 10 TOTAL MRT modules (M ) System for R&D (M ) System for Production (M ) 5 0 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 (Source: Yole estimation based on interviews) Since 2010, the R&D system market is bigger than the MRT module market in terms of value In comparison, the production market (in M) is much higher due to the ASP. 2011 14
Market Segmentation 2011 15
S curve: Batch Technologies & Flow Chemistry Measure of Performance Added value of Flow chemistry is really depending on the application Possible applications: - Library synthesis - Hazardous and reactive species - Discovery of new reaction paths - Scalability - Production - On site production Flow Chemistry Batch Chemistry Point at which emerging technology is competitive with the previous one Time Measure of effort invested 2011 16
Market Segmentation Segmentation is a market tool used to provide a vision of the market The segmentation is based on interview data and Yole Développement knowledge in microfluidics technologies and Chemistry fields. Technical and behavior criterions are used in order to create a segment Each segment includes players that have same needs. Therefore, these can be approached in the same way Identification and analysis of the different applications Technical criteria: Optimization or Exploration Behavioral criteria: Depending on the molecule life cycle Behavioral criteria of analysis Technical criteria of analysis 2011 17
Behavioral & Economical Criteria In order to access the market, a molecule needs to pass through both research and development steps. Value Quality and yield improvement Increase safety Reduce cost Research step X X X Development step Production step X X X Reduce time to market X *Key points Production step denomination is not related to production volume but rather to the fact that the molecule has a commercial value on the market. End user behavior depends on the stage where the molecule is: while the main driver in the research step is safety improvement, in the development step it s time reduction and in the production step it s mainly the improvement of quality and sustainability (through cost reduction) of processes. 2011 18
Technical Criteria Batch Technologies Flow Technologies Examples of potential applications Linear reaction x High reaction parameter control Easy scalable reaction for early development testing x Drug discovery (kgs API (Active Pharmaceutical Ingredients) for testing) Large production volume (>1000 t/year) x Multiphase reaction x some Reaction with solid, Catalysis On line analysis x The controlled addition of exact stoichiometries of reagents Safety for hazardous reaction x Azides preparation, azides reaction, hydrazoic acid, continuous dipolar cycloaddition Extreme condition reactions x High temperature, high pressure reaction Well controlled Gases-Liquid reactions x Ozonolysis Screening and optimization for library synthesis x Research Homogenous mixing x Gas-liquid reactions Excellent heat transfer x Exothermic reactions Production on user site (in situ): Avoid transport + storage X Phosgene, acrolein, interhalogen compounds, chloramine, hydrazines, Metalli-organic reagents, Azides, diazo compounds Expensive reactants x Early stage drug discovery Flow chemistry technologies can be used in order to answer different technical requirements related to different applications. 2011 19
Market Segmentation Technical criteria Optimization Exploration High reaction control Hazardous and explosive reactions Impossible reactions in batch Molecule life cycle Behavioral criteria Research Development Safety, reduce reagent cost Speed optimization S1: MRT for Library synthesis (Molecules synthesis) S4: MRT for scalability (Optimal reaction conditions) Production Cost Optimization S5: MRT for production S2: MRT for reactive species S6: MRT for on site production S3: MRT for the discovery of new reaction paths 2011 20
Molecule Life Cycle Possibilities If the research is done with flow chemistry technologies, the development will be done with MRT too Development conclusions Batch or Flow chemistry? Production in Batch 2011 21
Company and Product Examples 2011 22
Supply chain: Company Examples Material Suppliers MRT Suppliers Module Manufacturers System Manufacturers Engineering Companies End-Users R&D centers Module & System Manufacturers Equipment Suppliers Related equipment Manufacturers (pumps, collectors...) 2011 23
Ehrfeld Mikrotechnik BTS Modular MicroReaction System (MMRS) Research Application A flexible solution: Modules are arranged on a baseplate: mixer, reactor, heat exchanger, sensor and actuator, and interface modules. Tightened by clamping modules More than 60 different modules available Many different types of reactions can be realized Features: Materials: Stainless steel, Hastelloy Temperature: from -20 to 200 C Pressure: up to 100 bar Throughput: 0.1 to 500 ml/min Price: from 20 to 150k MMRS Application R&D and kilo lab (0.05-10 L/h) Process R&D Preclinical phase MMRS with extensions 2011 24
Syrris Asia System Research Application Asia is a modular flow chemistry system making it ideal for both beginners with modest budgets and experts who demand the utmost functionality. System exists in 3 versions Asia 2-series includes total automation of reaction temperature, reaction time, flow rates and single product collection. Features: Materials: glass or quartz 2 automated reagent injection loops High temperature microreactor heater Solid phase chemistry reactors and heater adaptor Preparative scale tube reactor and heater adaptor Price: from 20 to 100k Application Ideal for introduction to the world of flow chemistry Kinetic, yield optimization, one step process Asia 2-series system 2011 25
Chemtrix Kiloflow Development Application Kiloflow is an intermediate system between research and production. It was launched in 2011 by Chemtrix. The system includes several MRT components, micro pumps and software Price for a complete system: 95,000 Applications: Pilot Plant for process development Can be used in production phase Chemtrix-Kilofrow Features: Glass meso reactors Production volume: several Kg/day Reactor volume: up to 1L (Source:Chemtrix) 2011 26
Microinnova Flow Miniplant Development Application Microinnova Flow miniplant is an intermediate system (100 kg to ton scale). - The S-Class has a strong focus on scalable process development in the laboratory, including small pilot testing. - The M-Class is focused on the piloting of large processes in a range of several tons per hour and is also applicable for small scale production This product was launched in 2011 Price: ~ 100k Features Microinnova-Flow mini plant Material: stainless steel Flow rate: 1-10 L/h operating pressure: 0 to 20 bars operating temperature: -20 C to +200 C 2011 27
Corning NIM reactors Production Application Corning NIM reactors Features: Material: glass Integrated thermal management Enhanced mixing properties Low pressure drop Convective/chaotic mixing Channel size: ca. 500µm diameter Flow: ca. 50 ml/min Corning NIM reactors type A Multi purpose flow reactor in production: 2 banks with 4 lines each and 96 fluidic modules in total. Numbering up solution P Pochlauer, presented at Scale-up conference organised by Scientific Update, Vancouver, 2009 2011 28
Alfa Laval ART Plate Reactor Production Application The Plate Reactor is ideal for a wide range of applications within the fields of pharmaceuticals, fine and specialty chemicals. To use for chemical liquid/liquid reactions, exothermic reactions and for reactions completed within minutes. The ART Plate Reactor is a multipurpose reactor that is easily reconfigured to fit different reactions. The unit is easily opened for cleaning and inspections. Key features Material: stainless steel 20-500 l/h Modular design Multi-purpose unit Possible to open and clean High efficient for mixing and heat transfer Good plug flow Ability to monitor the process Easy to scale from lab to production (gram to multi-ton production) Used in production, including cgmp Alfa Laval ART Plate Reactor 49 Scientific update 2011 29
Current Market Status and Perspectives 2011 30
Top 10 Fine Chemical Companies MRT Company Headquarter Country 2010 Ranking 2010 Sales ($M) Involved in MRT BASF Germany 1 2.654 X Evonik Germany 2 2.611 X Lonza Switzerland 3 2.370 X DSM Holland 4 1.725 X Sumitomo Japan 5 1.028 X SAFC USA 6 647 X Saltigo Germany 7 637 X Albermale USA 8 569 X WeylChem Germany 9 398 NA Novasep France 10 345 X (sources: The Fine Chemical Benchmarking Service (May 2011) & Yole Developpement) 2011 31
Top 15 Pharmaceutical Companies in 2010 MRT 2010 Top 15 Pharmaceutical companies by sales in $ billion Rank Company Country Total 2010 Revenue, in $B 2010 Revenue Pharma, in $B Involved in MRT 1 Pfizer US 67.8 67.8 X 2 Novartis CH 50.6 50.6 X 3 Merck DE 46 46 X 4 GSK UK 44.3 44.3 X 5 Sanofi-Aventis FR 40.7 40.7 X 6 Roche CH 50.8 39.7 7 AstraZeneca UK Se 33.3 33.3 X 8 Abbott US 35.2 25.4 9 Eli Lilly US 23.1 23.1 X 10 Johnson&Johnson US 61.6 22.4 X Bristol-Myers 11 Squibb US 19.5 19.5 12 Takeda JP 15.8 15.8 X 13 Boeringer Ingelheim D 12.6 12.6 14 Astellas JP 11.5 11.5 15 Daiichi-Sankyo JP 10.5 10.5 total 463.2 Global pharma market 791.449 *related to exchange rate at the end of the exercise date (source: Yole Developpement) 2011 32
MRT Product Portfolio Most of the MRT are used for research applications today! Mass Market Niche Market Production applications Development applications Research applications Mass Market 2011 33
Conditions for Sustainable Growth 2011 34
From Actual Weakness to Potential Solutions WEAKNESSES POTENTIAL SOLUTIONS Knowledge is still limited Weaknesses After proof of concept, proofs of economical advantages are required Technical limitation around MRT (downstream processes ) Find the right arguments to communicate Involvement in education Increase conferences with prospects participation Weaknesses Business Cases for specific Applications are needed Anticipate today what will be the limitations of tomorrow Green Chemistry is not a must but a nice to have 2011 35
Example of Current Limitation: Production Volume One of the limitations for flow chemistry technologies is the limitation in terms of production volume In order to answer this problem, two main possibilities: Scale up Increase the production volume by modifying the design of the channel with an increase of the diameter. Number up Increase the production volume by multiplying production systems parallel to each other. In this case, the diameter of the channel remains constant. 2011 36
Example of Current Limitation: Production Volume Scale up Number up Advantages No clogging Cost effective solution Easy management of fluid in the channel (flow distribution) Unlimited possibilities Keep the geometry of the microstructure Flexibility, possibility to add channels up to the required throughput Less risk for the company if the market was overestimated Issues Necessarily limited Heat transfer Flow and residence times do not obey the same scaling rule: new manufacturing methods are required. A compromise has to be done, and the process has to be validated again. Kinetics of the reaction change Difficult to control flow distribution among volumes unless actively controlled. Installation can become very bulky Instrumentation costs increase significantly 2011 37
Conclusions 2011 38
Conclusions The market of MicroReaction Technologies (MRT) dedicated to flow chemistry sharply increased over the last five years. The recent and growing involvement of the fine chemical and pharmaceutical industry clearly signals the transformation of this technology from academic settings towards applied research and production. The added value of the Microreaction Technologies is highly depending on the aimed application. The market segmentation gives the ability to understand to which segment a prospect belongs is essential as it determines the most appropriate offer and commercial approach. Sustainable growth of Microreaction Technologies Market will be possible only if MRT are widely use in Production. 2011 39
Thank you Q&A 2011 40