Giorgio Borghi ‐ MD MATRIC Europa

Cortona – September 2010

MATRIC EuropaMATRIC EuropaLife‐Changing Innovation

Process Optimization Center ConceptSolution Providers

WHY FLOW CHEMISTRY?

MAIN ADVANTAGES OF FLOW CHEMISTRY:

• YIELD & SELECTIVITY INCREASE.• MORE EFFECTIVE PROCESS CONTROL.• MORE UNIFORM PRODUCT QUALITY.• REDUCED NUMBER OF « TOUCHES ».• INCREASED SAFETY.• ELIMINATE INTERMEDIATE STORAGE (FOOTPRINT,

CAPITAL).• FACILITATE « REACH » COMPLIANCE.

ALL OF WHICH RESULT IN REDUCED COSTS.

Reactor type Temperature Residence Time YieldFlask, 0,5 l -40°C 0,5 h 88%Production (stirred vessel, 6m³) -20°C 5 h 72%

Microreactor (lab) -10°C < 10 s 95%

5 Minireactors (production) -10°C < 10 s 92%

:

Courtesy H. Wurziger, Merck KGaA

- Improved solvent use - Reduced energy consumption - Reduced capital, less space - GREENER PROCESSING‐ Flexible production‐ SHORTER TIME TO MARKET.‐ EXTENSION OF PATENT LIFE.

Early Industrial Production Unit at Merck inGernsheim, 2002

WHY MICROFLOW CHEMISTRY?

MANY DIFFERENT TYPES OF MICROREACTORS ALREADY EXIST

• CORNING SAS (F)

• IMM (D)

• TNO (NL)

• CHEMTRIX (UK, NL)

• AM TECHNOLOGY (UK)

• VAPOURTEC (UK)

• LITTLE THINGS FACTORY (D)

• ……….

MODULE LIBRARYMODULE LIBRARY

Stacking scale‐outGen I

Gen III scale‐out

Gen II scale‐out

Gen I, II, III Production banks

MOST NEW PLANTS BASED ON MICROPROCESSING ARE BEING ESTABLISHED IN THE FAR EAST AND INDIA

• NEED TO UNDERTAKE RE‐REGISTRATION PROCEDURES WITH AUTHORITIES DUE TO PROCESS CHANGE

• LACK OF INTEREST DUE TO “SUNK CAPITAL” SITUATION• OUTSOURCING WITH “TRADITIONAL” CMO’s• LACK OF INTERNAL KNOW‐HOW• RELUCTANCE TO ENGAGE CRO’s (FEAR OF IP LOSS)• LACK OF HUMAN AND CAPITAL RESOURCES FOR RESEARCH AND

DEVELOPMENT

BARRIERS TO SHORT TERM ADVANCES IN MICRO-CONTINUOUS PROCESSING

REASONS CITED BY PHARMA COMPANIES FOR RELUCTANCE TO INTRODUCE NEW MICROTECHNOLOGIES

EXPLORE THE CONCEPT OF AN INDEPENDENT REGIONAL PROCESS OPTIMIZATION RESOURCE CENTER THAT WILL HAVE PROVIDE ACCESS TO THE DEVELOPMENT OF NEW TECHNOLOGY FROM:

• UNIVERSITIES• INDUSTRIAL CONSORTIA• NATIONAL LABORATORIES• RESEARCH INSTITUTES• VENDOR COMPANIES

MATRIC EuropaMATRIC EuropaMISSION:Independent innovation organization servicing European and International manufacturers – Focus on Chemical, Energy and Environmental Technologies

• API and specialty chemicals manufacture• Green chemistry• Alternative energy and energy efficiency• Pollution control

– Unique Capabilities and Impacts• Process Innovation• Process Integration• Process Intensification

Basing its commercial viability on contract work and development of Intellectual Property– Built on successful business model from United States

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MATRIC - MIDDLE ATLANTIC TECHNOLOGY, RESEARCH AND INNOVATION CENTER

• MATRIC is non‐profit research and development corporation formed in 2004– Reinvest earnings in new research– Offices in throughout the USA

• Research and engineering staff of over 150– 40 PhD‐level researchers– 25+ average years of experience– 2 members of National Academy of

Engineering• MATRIC has a focus on developing Intellectual

Property for commercial and industrial customers

• Significant portfolio of over 100 projects and a variety of customers– Large industrial customers (Chevron,

Exxon, Dow, UOP)– Small innovation companies (BEST

Energies, DNP, Novamer)– Government agencies (Energy, Defense,

NASA, EPA)

MATRIC was formed from the downsizing of

over 2000 research scientists and

engineers located at the Union Carbide Tech

Center, South Charleston, WV from

2001-2008

MATRIC’S THREE STEP APPROACH TO TECHNOLOGY COMMERCIALIZATION

1. Do the necessary research, development and engineering to define the technology, process or product.

2. Develop an intellectual property (IP) package which defines the technology, process or product, and if warranted, develop and carry out a patent strategy.

3. Either start up a new company to carry out the commercialization or license the IP, receiving royalties for its use. Two licenses and 12 companies started using MATRIC intellectual property

MATRIC GREEN CHEMISTRY ACTIVITIES• DEVELOPED A CONTINUOUS BIODIESEL PROCESS THAT CAN USE CRUDE CORN OIL

AS WELL AS CRUDE SOYBEAN OIL• Developed a process to produce isosorbide from corn• Developed new technology for refining fermentation ethanol that decreased energy usage by 40 percent• Developed a process to produce a fermentation based deicer• Made major improvements in the production of green polymers for two different companies• Developed a low cost “green solvent” for coke production from coal for the steel industry • Developed a biodegradable slide release agent for prevention of coal adhering to the sides of rail cars• Solved some difficult solids handling and processing problems for a company with a large scale cellulose to ethanol

pilot plant

• DEVELOPED A NEW BULLET PROOF PLASTIC THAT CAN REPLACE POLYCARBONATE • DEVELOPED A PROCESS FOR TREATING GAS WELL WATER• Developed Se removal technology for surface water

• DEVELOPING AL AND HG REMOVAL TECHNOLOGIES FOR SURFACE WATERS • CO/CO2 utilization to make novel “green” polymers• Anaerobic digestion of farm wastes to produce energy and value‐added products (Bioplex)• Algae‐based fuels and products• Inherent safety improvements in manufacture of highly reactive intermediates• Olefins production from natural gas• Use of oxy‐fuels for co‐production of power & chemicals• Novel technology approaches for CO2 and SOx capture• Biomass to gasoline• Ethanol to more efficient fuels & specialty chemicals• Novel biobased routes to acrylate products

MATRIC Europa located in the

Insubria BioPark at Gerenzano

– Former multi‐national pharmaceutical research complex outside of Milan

– Available chemical and biological laboratories

– Utilizing technology developed at MATRIC, CPAC and other research centers

AFR evaluation tool: flexible with capability all the way to pilot scale

A3

A2A1

A5

A4

Standard Reactor Blocks A + B :• 1 SJI • 2 SJH• 6 RTH

Reactor Block A

Reactor Block B

CURRENT GERENZANO LABORATORY REACTOR SET‐UP

Corning LFR

LFR = Low Flow Reactor

Research and Engineering Enterprise

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Supporting Processes

MATRIC Europa

Ability to offer innovation from laboratory discovery through operation of full scale production

Summary

• MATRIC Europa has access to a depth of expertise in process development at all scales– Special focus will be on the use of microreactors and

process analytical technology (PAT) for pharmaceuticals and fine chemicals

• MATRIC Europa’s labs in Gerenzano offer the ability to test new chemistries and processes quickly and efficiently

VendorCompanies

Trade Associations European Union Government

Provincial and National

Government Agencies

EngineeringOrganizations

Research Universities, Institutes and Consortia

TitleMATRIC Europa

Key PartnershipsKey Partnerships

MATRIC Europa 23

LEVERAGING THE FULL CAPABILITIES OF MATRIC AND CPAC IN THE US

REACTORS AND PAT ARE ONLY PART OF THE STORY:

PROCESS INTENSIFICATION REQUIRES THE INTEGRATION OF REACTORS, SEPARATION TECHNOLOGY AND ANALYTICAL TECHNOLOGY.

Thank you

MATRIC Europac/o Biopark Insubrias – via Roberto Lepetit 34 21040 Gerenzano (VA), Italycontact: giorgio.borghi@matriceuropa.comwww.matricresearch.com/MATRIC‐Europa.asp