© Maksym Yemelyanov - stock.adobe.com Company News Global Biologics CDMOMarket, European ChemicalCompanies, M&A: Asian Investment in Markets &Companies Biosimilars Threatens CompaniesBiosimilars Threatens PriceInterfaces, Erosion for andat inSolutions Surfactants Chemicals inCircular Economy, Strategy &Management FINE I I I I I I I I I I I I I I I I Digital Chemical Sales Processing Control, inQuality Technology,Reaction Image andMicro Flow Chemistry Technology &Innovation CHEMICALS SPECIALTY & N N N N N N N N N N N N N N N N N N N N N

2019 1/ 34th International Exhibition for Fine and Speciality Chemicals

26 – 27 June 2019 | Messe Basel, Switzerland

Fine and speciality chemicals for various industries Europe’s most renowned industry hotspot

Meet suppliers and experts from around the globe and find bespoke solutions, new approaches and innovative substances for your enterprise.

fine chemicals • agrochemicals • pharmaceuticals • adhesives & sealants • paints & coatings colourants & dyestuffs • flavours & fragrances • pulp & paper chemicals household & industrial cleaning • leather & textile plastics additives • food & feed ingredients cosmetics • polymers • surfactants water treatment • petrochemicals electronic chemicals and much more

Top conferences • Agrochemical Lecture Theatre and workshops offer • Chemspec Careers Clinic • Pharma Lecture Theatre valuable insights • Regulatory Services Lecture Theatre into ongoing • RSC Lecture Theatre R&D projects! • Innovative Start-ups

www.chemspeceurope.com Organisers: C o n t e n t

©Bits and Splits - stock.adobe.com

Technology & Innovation

Cheaper, Faster, Smaller, Cleaner 18 Prospects of Flow Chemistry for Fine & Specialty Chemicals and Pharma ©manop1984 - stock.adobe.com Volker Oestreich, CHEManager

Flow Chemistry: Key Technology for Sustainable Processes 20 Experts Discuss Challenges and Opportunities Markets & Companies of Micro Reaction Technologies Experts of BASF, Clariant, Ehrfeld Mikrotechnik, Asian Interest in European Chemical Firms 4 ©alphaspirit - stock.adobe.com Innosyn, Microinnova, Patheon, Sanofi, Syrris, Chemical M&A Buoyant after a Record Year in Asia and Università di Perugia share their opinions Bernd Schneider, Alantra Chemical Sales Going Digital: What to Expect? 23 The Missing Piece 6 Strategy & Management Are the New Digital and Global Opportunities in Chemicals in Circular Economy Chemicals more Threat or Possibility? Anne-Sofie Bäckar, ChemSec The R&D Footprint of the Chemical Industry 13 Alexander Lakemeyer, Pinpools Chemical R&D Spending Generates Long-Term Benefits A Better Way to Use Resources 8 for Society at Large Analyzing Pores Deep-Down 24 At Nouryon, Circular Projects Are Linked to Quality Control of Porous or Granular Substances Improving the Existing Value Chain The Need for Innovation in with Modern Image Processing Interview with Marco Waas, Nouryon Pharmaceutical Manufacturing 14 Daniel Balser, Strelen Single-Use Technologies and IIoT Solutions in Imagine Chemistry 2019 Generates 162 Ideas 9 Biopharmaceuticals Manufacturing Unmesh Lal, Frost & Sullivan Solving Challenges at Interfaces 10 EVENTS 26 Surfactants are used in a Variety of Biosimilars: The Price Challenge 16 Applications from Detergents to Cosmetics to Market Prices Have Come Down Significantly – IMPRINT 26 Crop Protection to Oil & Gas How Much Can Copycat Makers Really Earn? Staffan Asplund, CESIO Thorsten Schüller, CHEManager INDEX 26

Cover Page

Periodic Table of Chemical Elements turns 150

The Periodic Table of Elements is anniversary, 2019 has been desig­ Qi-Feng Zhou, IUPAC president, mistry and show creative ideas on one of the most significant achie­ nated by UNESCO as the Internatio­ calls the periodic table “a map of this topic. The cover page of this vements in science. 150 years ago, nal Year of the Periodic Table (IYPT our knowledge, particularly in che­ edition of CHEManager Internatio­ Russian chemist and inventor Dmitri 2019). mistry, and a symbolic representa­ nal shows the periodic table to re­ Ivanovich Mendeleev created his far­ The discovery of the “periodic tion of the process of scientific re­ cognize its importance for gene­ sighted version of the periodic table. law” by Mendeleev and the creation search.” rations of chemical researchers. He used it to correct the properties of the tabular display of the chemi­ ChemPubSoc Europe, a part­ Without Mendeleev’s invention 150 of some already discovered elements cal elements in order of increasing nership of 16 continental Euro­ years ago, science would have ta­ and to predict the properties of eight atomic number has since been of pean chem­ical societies, and Chem­ ken a different route or at least a elements yet to be discovered. ines­timable value in the develop­ istryViews.org are highlighting the detour and many discoveries that The year 2019 marks the celeb­ ment of chemistry. Naming them all 150th anniversary of the 150th an­ have led to innovation and pro­ ration of the 150th anniversary of the would go beyond the scope of this niversary of the periodic table to gress would probably have never periodic table. On the occasion of this note. raise global awareness of che­ been made. (mr)

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Asian Interest in European Chemical Firms Chemical M&A Buoyant after a Record Year in Asia

The chemical industry is one of the most international sectors with slowed down in the fourth quar­ activity dominated by cross border transactions. Chinese and other ter, but the first nine months saw 23 transactions­ of which, for ex­ Asian firms have been particularly busy expanding their global foot- ample, ten in the consumer or a res­ print and taking advantage of the quality assets for sale. pective seven in the business services and energy, mining and utilities sec­ tors. By contrast, transactions in the US plummeted 94.6% to $3 billion Bernd Schneider, Worldwide, geopolitical tensions trade wars with the US caused a dra­ last year from a record $55.3 billion Alantra and slowing global economic growth matic shift in deal flow. Europe be­ in 2016, according to Mergermarket took its toll in terms of the number came the preferred destination with ­figures. of deals, according to Mergermarket The motives behind European presence in the plastics industry data for fiscal year (FY) 2018. How­ transactions are the same as those ­beyond chemicals trading and fertili­ ever, deal volumes jumped 11.5% to driving other global purchases — zer production. $3.53 trillion in 2018 compared to “Chinese and other Asian to close the gap through acquiring the prior year while more specifically firms have been particularly technological prowess as well as ex­ the Asia-Pacific (excl. Japan) M&A busy expanding their global pertise, proprietary formulations Growing Investment Interest ­region recorded 4,036 deals totaling footprint and taking and products. One example is the in Sustainable Industries $717.4 billion, a 2.6% hike over 2017. roughly €200 million sale of Euro­ Overall, the industrials and chem­ advantage of the quality pean engineering plastics specialist It has been well documented that icals sector was the most attractive assets for sale.” Elix Polymers by Sun European Part­ the Chinese economy is slowing to sector in 2018 by both value and vo­ ners to Beijing-based Sinochem. The 6% growth from an originally fore­ lume. The final tally was 318 deals deal supports the ABS Compound casted 6.5%, but growth is still re­ priced at $68 billion, compared to producer’s strategy to expand its ac­ latively robust compared to the low $82 billion across 321 deals in 2017. Chinese acquisitions in the region tivities in Asia, a region in which it is single growth figures of many deve­ China continued to be an active surging 81.7% to $60.4 billion from currently underrepresented. At the loped countries. Chinese companies participant although the on­going $33.2 billion in 2017. Deal­making same time, it will boost Sinochem’s will continue to look for opportunities ©manop1984 - stock.adobe.com

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in traditional chemical segments, but ger a wave of restructuring resulting stock market. Medium-sized com­ Bernd Schneider, managing di­ they are also interested in buying or­ in new strategic plans and the hiving panies in the US and Europe such rector and global head of Chem­ ganizations involved in pollution, wa­ off of subsidiaries. Specialists and as the German Mittelstand would icals, ­Alantra, Frankfurt am Main, ter and waste treatment solutions as ­niche companies would be particu­ be especially interested in them be­ Germany well as green and sustainable chemi­ larly attractive not only due to their cause many missed out on getting a cals and plastics. sharper competitive edge and tech­ foothold in the Chinese market due This is being driven by the nological expertise but also lower to increasing prices during the first [email protected] government’s new environmentally- valuations on the back of a weaker wave of M&A activity. www.alantra.com friendly laws under the 12th Five- Year Plan which aims to clamp down on unsustainable industries and in­ centivize clean and green energy businesses.

Chinese Government Influence Your wish our goal We are a dedicated custom manufacturer for hazardous chemical reactions While the flow of deals has mainly been from China to the West, the such as Nitration and Phosgenation (COCl2). Our team of experts looks tide has not been just one way: Glo­ forward to helping you in all your needs for chemical intermediates and APIs. bal conglomerates are divesting Chi­ nese operations as well. As always, high quality assets are constantly in demand, such as the Hovione/Imax deal. But tighter government regu­ lations have increased costs for com­ panies and spurred divestment dis­ cussions. The Chinese government has clearly stated it intends to standar­ dize chemical parks along the lines of global industry best practice. Cur­ rently, only about half of the chem­ical production plants in China are in de­ dicated chemical parks, but this pro­ portion is expected to increase dras­ tically by 2020, with some provinces having set targets of 90% or more. Western companies, especially those who do not obtain a permit to in­ crease capacity, are increasingly ex­ ploring all options for their assets instead of moving to one of the new parks. The domestic industry is also set for a further bout of consolidations. Last year already saw Chinese chem­ ical product manufacturers Yantai Wanhua and Wanhua Chemical join­ ing forces in a $12.7 billion tie-up, but anticipation is running high for the merger between Sinochem and its rival Chemchina, which completed China’s largest outbound deal a year ago with the $44 billion takeover of Swiss agribusiness Syngenta, a deal in which Alantra was involved. The transaction, which would produce an oil-to-chemicals giant with more than $100 billion in assets, has been in the works for at least two years and would eclipse Germany’s BASF, the world’s largest maker of industrial Société Suisse des Explosifs Group chemicals, by sales. Fabrikstrasse 48 / 3900 Brig / Switzerland If completed as anticipated, the VALSYNTHESE SA T +41 27 922 71 11 / [email protected] / www.valsynthese.ch deal is expected to significantly change the landscape of China’s chem­icals industry. It is likely to trig­

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The Missing Piece Chemicals in Circular Economy

The concept of circular economy has long been a staple in the vo- higher volatility. This will lower mar­ cabulary of anyone who wants to come across as at least some- gins and profitability for companies and increase consumer prices in the what progressive. Today, circular economy is more than just a buzz- long run. word. One crucial, but often overlooked part of a circular economy The idea of a circular economy is to manufacture components, artic­ is the role of chemicals. While considerable efforts are being made les and products that can be perpe­ to reduce pollution and depletion of the earth’s resources by simply tually disassembled and re-used, thus Anne-Sofie Bäckar, creating a no-waste society and mi­ ChemSec increasing recycling, little attention is paid to the contents of the old nimizing the strain on natural re­ products that we turn into new ones. sources. To simply use and discard is no ­longer a viable option. To achieve prosper due to environmental suc­ cess, not despite it. There is a need for a change in the business mindset, so that company interests, societal needs and environmental challenges are merged into one business idea. Since hazardous chemicals are common ingredients in all kinds of materials they obviously end up in recycled materials as well. This fact makes it virtually impossible to grow the market for recycled materials — the material transparency is simply too low for chemically progressive brands to want to reuse these mate­ rials in new products. The way forward is increased transparency on the chemical con­ tents of all materials. This informa­ tion should follow materials all the way to the waste phase. Used pro­ perly it will raise the price of recyc­ led materials. The end goal is to eli­ minate hazardous chemicals from waste streams through design and in­ novation, not dilution and costly risk analyses. The use of recycled material can only be profitable in the long run for

©Elnur - stock.adobe.com a company if it fulfills the same crite­ ria as virgin material. The truth is that today’s chemicals and stay away from toxic chemicals this change, however, both businesses legis­lations are not adapted for a sus­ in products and supply chains, many and society need to re-think the way tainable circular economy, as many companies have internal chemical re­ we make profits and design products. Product Planning and Design hazardous chemicals are unregu­ quirements that go beyond legal com­ In business, sustainability is some­ lated and in widespread use. These pliance. times seen as a necessary but never­ A smart design is the most critical chemicals fulfill thousands of diffe­ theless burdensome cost — not some­ stage in a product’s life cycle. The rent functions in all kinds of everyday most cost-effective approach is to se­ household items. And as these items Circular Economy as lect the appropriate materials and are the very same we recycle and Business Opportunity chemicals right at the drawing board, turn into new products in a circular “In a sound circular eco- before the product even exists. By do­ world, it also means we are recycling In our society, the prices of raw mate­ nomy, companies prosper ing this, toxic waste can simply be their toxic contents. rials and trash collection are increas­ due to environmental “designed out” and instead replaced Luckily, a growing number of ing because of physical limitations. success, not despite it.” by resources and products that can brands and retailers are realizing The resources available in the earth’s be utilized by somebody else. that, at the moment, legal compli­ crust are simply shrinking. The “take, The greatest obstacles to success­ ance is neither a good benchmark make, waste” paradigm within the li­ ful recycling are actually the original for corporate chemicals manage­ near economy has led us to a criti­ thing that actually strengthens the design and lack of information about ment nor for a circular economy. In cal point that also affects business, business idea and profitability. In a what chemicals were added to the order to account for weak legislation through higher commodity prices and sound circular economy, companies materials from the very beginning. By

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demonstrating knowledge and trans­ Systems like this can be used to TSCA. There are also many product- In current business models, re­ parency you add value to the product. include extensive chemical informa­ specific regulations in the EU and in cycled materials struggle to be com­ Products and materials that are de­ tion. The barcode system is another other regions for controlling hazar­ petitive with primary raw materials signed to be recoverable, recondi­ such example. It is technically very dous substances in products such as markets. This is often due to the fact tioned and upgraded have around easy to include chemical information electronics. that recyclers cannot deliver the level twice the value of products and mate­ in a system like this; all you need is But legal compliance does not gua­ of material transparency that many rials that are not, as they can be sold the information. The challenge lies in rantee automatic success in the circu­ brands are asking for. Recycling mar­ several times. implementation and standardization. lar market. In fact, this is far from the kets can only be sustainable if they By decreasing the hazardous con­ This change is happening already, truth. Even in the EU, which in many can assure that recycled materials tent of a product, you increase the as many brands with big purchasing ways has the most ambitious chemi­ do not contain toxic substances. Will­ possibilities for recycling and success power are pushing for more and cal regulation in place, substances ingness to support the development in the aftermarket. You also reduce more chemical transparency in the with hazardous properties are still in of non-toxic material cycles will thus the need for virgin raw materials and supply chain. By putting pressure on widespread use. This is because regu­ not only protect health and the en­ the energy costs to produce them. suppliers to increase chemical trans­ lation moves slowly, and it will take vironment but will also enhance the The novel idea that the circular parency and use safer alternatives, many years before REACh includes quality of secondary raw materials economy presents is that good de­ these companies serve as role models all the substances it intends to regu­ and boost recycling markets. sign is not only environmentally and and pave the way for other, smaller late. In addition, REACh does not fully Legally, in order to incentivize ­morally good; it’s also more profitable. companies to follow suit. cover the chemical content in articles high-quality recycling, there is a need As a consequence, chemicals man­ that are imported into the EU. to avoid creating a two-tier system agement should have a higher priority The regulatory system for chemi­ between virgin and raw materials, or on the corporate agenda. Depending Legal Compliance cal control is therefore not a relia­ between products and articles impor­ on company goals, chemical issues Is Not Enough ble guide for sustainable business or ted from the EU and those imported can be prioritized at different levels. At for identifying which substances are from elsewhere. the lowest, so-called reactive level you Just as hazardous man-made chemi­ compatible with a circular economy. Recycling should never be viewed simply follow regulations and adapt on cals are complex and wide reaching, This is why chemically progressive as a low-cost solution. It might sound the fly. By contrast, at the highest and so is the legislation set up to regulate companies are setting the bar higher contradictory, but setting identical, most ambitious level you actively seek them. than legislation and enforcing their strict rules for recycled materials will out green chemistry and sustainable The EU has enforced REACh (Re­ own chemical requirements for pro­ help them compete with virgin mate­ materials that position the organiza­ gistration, Evaluation, Authoriza­ ducts and supply chains. The num­ rials. tion for the circular economy. tion and Restriction of Chemicals), ber of such companies with their own It is a fact that regulation drives a comprehensive legal framework chemical standards is increasing, and innovation, and recycling is no excep­ that addresses all chemicals in use today represents sizeable chunks of tion. Putting the appropriate legisla­ Supply Chain Management, and requires companies that mar­ their respective industries. tion in place is not a burden, it will Transparency and Traceability ket chemicals to present a set of test provide clarity and is essential to es­ data. The US equivalent, TSCA (Toxic tablish a circular econ­omy. Since a product consists of com­ ­Substances Control Act), set some ba­ Reuse and Recycling ponents that are produced and as­ sic requirements but is much more li­ Anne-Sofie Bäckar, executive direc­ sembled by many different suppliers mited in scope. In many other parts of Many waste streams contain hazar­ tor, ChemSec, Göteborg, Sweden in the supply chain, it is impossible the world there are other regulations dous substances and should not be to communicate the chemical con­ in place to address chemicals, some recycled without a prior decontami­ [email protected] tent down the supply chain without aiming to be similar to REACh or nation step. www.chemsec.org ­proper information from the previous suppliers. The need for systematic chemical control up and down the supply chain is already a priority for many com­ panies. Unsurprisingly this need will only grow in the future as recycled materials are being circulated back into the production loop. Your partner in growth – since 1903 There are mainly two activities that are needed in order to approach the circular economy from a chemical point of view: ¨¨increase knowledge of the compo­ A leading distributor of specialty chemicals sition of products, and ¨¨phase out chemicals that do not fit with a truck fleet across Central Europe. within a circular economy. Looking for a local full service-partner with its own global sourcing network? As a family-owned business with more than 110 years of experience we strive to be your Some industries have already cre­ preferred supplier in the following industries: ated effective systems for transfer­ ring information between suppliers Food & Feed, PICAR, PTL, Home Care, Construction and Water Treatment. and users in the supply chain. The IMDS and BOM-check databases are What can we do for your segment? Find out on www.haeffnergroup.com already used in the automotive in­ dustry and the electronic industry respec­tively, and relevant parts may We are looking forward to welcoming you at the Chemspec Europe 2019 be accessed by everyone in the entire in Basel, Switzerland (booth G125) from June 26–27 2019. supply chain.

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A Better Way to Use Resources At Nouryon, Circular Projects Are Linked to Improving the Existing Value Chain

Availability and supply of essential resources for chemical produc- prove your resource & energy effi­ tion are getting increasingly challenging. At the same time, mankind ciency? has developed a throwaway mentality that is producing billions of tons of waste — waste that contains valuable resources in the form M. Waas: One project I like a lot is Waste-to-Chemicals. This is based on a of, for instance, biomass, plastics or scarce metals. All this calls technology from Enerkem to make for a circular economy. As many other chemical companies, Nou- methanol from household waste that Marco Waas, we cannot otherwise recycle. This is Nouryon ryon is looking for ways to create a more sustainable future through the type of technology that can really chemistry. Interviewed by Michael Reubold of CHEManager, Marco change the entire supply chain in the coming years. After 20 years, the tech­ istry. Our industry still gets a lot of its Waas, Director RD&I and Technology at Nouryon, discusses the nology is mature enough to scale up to raw materials from hydrocarbons concept of circular economy and describes projects that contribute factory size. With several partners we such as gas or oil. You can also get the are planning a plant in Rotterdam that carbon from other sources, such as to a more efficient use of resources and a better use of secondary will be able to convert 360,000 tons of waste or CO and CO2 emissions from raw materials from waste. waste per year into 209,000 tons of steel factories, but for optimal use methanol for the chemical industry. you need to add hydrogen. So, this is where we come in. For example, Tata Steel can use our green hydrogen, In a another, much-respected pro­ produced from water and renewable CHEManager: Mr. Waas, Nouryon ergy efficiency and renewable energy ject, Nouryon is partnering with electricity, to turn their waste gases has embraced the circular economy are therefore key to securing a relia­ Tata Steel and the Port of Amster­ into useful chemicals. With green hy­ in its sustainability agenda. How do ble energy supply in the long term. dam to study the feasibility of a drogen, waste carbon becomes a val­ you implement this concept into the Our circular projects are all linked to “green” hydrogen cluster in the uable raw material instead of a corporate strategy? improving our existing value chain by Amsterdam region. What potential wasteful emission to the atmosphere. looking at a better way to use re­ do you consider green hydrogen to sources. Ultimately, sustainability is have for building and contributing Marco Waas: Sustainability has to be business and business is sustainability. to a circular economy? You are building a demonstration an embedded strategy, not a separate plant to produce chemical building program. For example, our chlor-al­ blocks from carbon dioxide and kali and chlorate businesses are very What are the most interesting pro­ M. Waas: Green hydrogen is really sunlight at Delfzijl, the Netherlands, energy intensive and our efforts in en­ jects currently under way to im­ the game changer for circular chem­ with partner firm Photanol. Do you ©TSUNG-LIN WU - stock.adobe.com

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expect such processes to eventually ICOS III, has recently announced an decrease risk. When you look at the — products in the future. How will solve the climate problem caused by investment in Holiferm. We do this entire value chain of the project, from the current volume-based business

CO2 emissions? with the aim of ultimately making raw material to end product, there model of the chemical industry have better and cheaper bio-surfactants are often a lot of hidden opportuni­ to change in order to “earn more available to our customers. ties, which is another reason to pur­ with less”? M. Waas: This technology will contrib­ sue these projects in partnerships. ute, by using CO2 as a raw material — effectively turning chemical produc­ M. Waas: I think the chemical industry tion into a carbon sink instead of a „Sustainability has to be an After the split from AkzoNobel, Nou­ is now entering an entirely new carbon emitter. But one technology will ryon is private-equity-owned and growth cycle based on circular chem­ not solve climate change. We need to embedded strategy, not a under scrutiny of the investors. How istry. In the 1960’s, we were focused work together on all fronts and really separate program.” — and when — will the circular eco­ on investing in new materials, such as go for a joint transformation of our nomy projects pay of in terms of fi­ plastics. Then it was all about mass petrochemical and heavy industries. nancial success? production and making product af­ fordable for a growing world popula­

Collaboration across CO2-intensive tion. The next wave of innovation will You are actively participating in the industries is also a major trend in M. Waas: There are a number of tech­ be focused on circular chemistry, to trend of collaborative and open in­ the aim to battle climate change. nologies coming to maturity that can make affordable products for the novation by partnering with other Nouryon, together with partners contribute in the coming years. The world population in a sustainable way. companies as well as academia and from research and industry, is par­ Waste-to-Chemicals plant in Rotter­ research organizations. How does, ticipating in the publicly funded dam can be operational in three years’ for instance, Nouryon’s Imagine Carbon2Chem project coordinated time for example. Production of green Several projects lead to savings in Chemistry initiative contribute to by German steel producer Thyssen­ hydrogen is another example. This is energy costs, but others are adding developing more sustainable chemi­ krupp. What is Nouryon’s contribu­ based on electrolysis technology and extra costs to products. At the end cal platforms for your customers? tion and intention here? we already operate several large- of the day, you will have to ask your scale electrolysis facilities to produce customers to remunerate you for your investments in more sustaina­ M. Waas: Imagine Chemistry helps us M. Waas: This is another example of ble and efficient products. How do become a more reliable and valuable using CO and CO2 with green hydro­ you rate their readiness to do so? partner to our customers by bringing gen to make methanol and other “The chemical industry in outside innovations. For example, chemicals. Nouryon is contributing is now entering an entirely we are working with a start-up, Semi­ technical and operational expertise in new growth cycle based M. Waas: Our customers are looking otic Labs, to use predictive algorithms water electrolysis and the conversion for a reliable partner to supply them on circular chemistry.” at our factories so we know when to of syngas to methanol. with essential chemicals, and our in­ replace or repair critical equipment. novations are supporting this. When By bringing in this knowledge from it comes to pricing, European society outside the chemical industry, we can Which guidelines do you apply to chlor-alkali. I therefore see no large is increasingly seeing carbon emis­ reduce downtime and improve the re­ allocate R&D budget to a circular technical obstacles for the deployment sions as a cost, which is reflected in liability of our plants, which is a huge economy project and evaluate the of water electrolysis for hydrogen pro­ energy and carbon prices. Energy ef­ asset to our customers. progress? duction. I cannot predict market ficiency projects are making us more Another example is our partner­ prices, but in the current socio-eco­ cost effective, not less. The same will ship with Holiferm, one of the winners nomic climate I think the transition of apply to circular chemistry in the of the Imagine Chemistry challenge in M. Waas: We start by looking at the the industry can also be a major op­ long run. Many technologies are only 2017. They have a new process to im­ strategic fit with our business and as­ portunity for long-term growth. now scaling up — imagine what it prove fermentation processes to make sessing the return on investment, would mean when we make our prod­ surfactants from bio-based sources. both short and long-term. On bigger ucts from wind, water and waste. We have helped them on the road projects with a longer horizon we of­ The term “do more with less” imple­ from a lab setting to a real start-up. ten work with partners to increase ments that we will need less materi­ Our Collaborative investment fund, the chances of project success and als to produce the same — or better www.nouryon.com

Imagine Chem­istry 2019 Generates 162 Ideas

Imagine Chemistry,­ the collabora­ event in May at its RD&I center at De­ The challenge is a key part of try Federation (CPCIF), seed investor tive innovation challenge of Nou­ venter, the Netherlands, where they Nouryon’s even greater focus on inno­ High-Tech Gründerfonds, venture ca­ ryon (formerly AkzoNobel Specialty will work with company experts and vation the company’s Chief Technology pital firm Icos Capital, research and Chem­icals) now in its third year, was business leaders to further develop Officer, Peter Nieuwenhuizen, said. advisory firm Lux Research, multi-sta­ launched to tackle chemistry­ -related their ideas into a joint value case. “We believe in the power of innova­ keholder collaboration Green Chem­ challenges and uncover new ways to The 2019 edition of Imagine tion and collaboration to drive growth istry & Commerce Council, UK inno­ create value for customers. For this Chem­istry set challenges in the areas: and create sustainable solutions for vation agency Knowledge Transfer year’s edition, more than 160 inno­ sustainable bio-based surfactants (in our customers. Our Imagine Chem­ Network, Brazilian content portal vative ideas from 30 countries were partnership with Unilever), perfor­ istry program helps bring innovative Startupi, Dutch accelerator Startup­ submitted by start-ups, scale-ups, mance-boosting nanoparticles, sen­ solutions to the next level and helps us Delta, the European Commission’s university spin-outs, and other poten­ sing in demanding chemical­ environ­ better meet our customers’ needs.” Enterprise Europe Network, and S/ tial partners. ments, label-free chemistries,­ and This year’s edition of Imagine park, the chemical­ technology-focused Nouryon will select up to 20 fina­ pushing the frontiers of chemical­ in­ Chemistry­ is supported by Unilever, open innovation center located at lists to attend an intensive three-day novation. China Petroleum and Chemical­ Indus­ Nouryon’s RD&I site in Deventer. (mr)

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Solving Challenges at Interfaces Surfactants are used in a Variety of Applications from Detergents to Crop Protection to Oil & Gas

Surfactants are used in a wide spectrum of applications. This broad range of use, among other things, will be at the center of in- terest of the 11th World Surfac- tants Congress to be held in Mu- nich in early June 2019. Staffan Asplund, president of CESIO, the European Committee of Or- ganic Surfactants and their Inter- mediates, and Surfactants R&D Director at Nouryon, provides a status report on the surfactants business and technology.

More than 50% of the surfactants which are sold in the EU are used for household detergents, by far the lar­ gest application in terms of volume and total market value. We assume that approximately 10% are used for personal care as well as for textile fi­ nishing. Another 5% are I&I applica­ tion — so we can say that three quar­ ters of the total volume are sold to four fields of applications. The remai­

ning 25% are used in many specific © CESIO applications, e.g. crop protection, le­ ather and paper manufacturing, oil­ field or the construction industry. In specialties has led to more complex tants are the basis to solve challenges terms of sales value, the picture is chemistries requiring more proces­ involving all kinds of interfaces and quite similar, though specialized per­ sing time, which has compensated applications. Surfactants are the key formance products tailored to speci­ the growth and stabilized the total to providing successful solutions for fic applications will trade at a higher output of surfactants on a high level. consumers, e.g. related to cosmetics unit value. Staffan Asplund, Nevertheless, our growth expec­ or household applications, or for pro­ president, tations are “restrained positive” — in CESIO Executive the past we have discovered new ap­ A Mature Business with Committee plications for existing surfactants and “Just as surfactants work Modest Volume Growth industry continues to innovate in this way. We develop new business models across interfaces, so innova- What we can derive from the publis­ that are not necessarily based on gro­ tion happens at interfaces.” hed production figures of our indus­ Whether there is a recession or wing volumes, but on higher effec­ try, the overall market situation for a peak in our business trends, the tiveness of the surfactant systems. surfactants in Europe is stable, with consumers still need food, do their fessional uses such as I&I or agroche­ limited growth in specific areas. This laundry, wash the dishes, use per­ micals and many others. This is be­ situation has been consistent over sonal care products and wear tex­ Performance — Solution — cause surfactants, are fundamental to the past few years. But if we look tiles. They may spend more money Success — Surfactants achieving the desired product perfor­ into the different surfactant groups in a booming situation and buy less mance. And just as surfactants work and applications, there is a general or cheaper products in a downturn, The congress theme of CESIO 2019 is across interfaces, so innovation hap­ trend from commodities to specialty but we can say that the overall sur­ „performance — solution — success pens at interfaces, not only between surfactants, which makes it even factant market in Europe is a mature — surfactants“. Surfactants in solu­ the science and application, but also more important to develop surfac­ business with modest volume growth. tions and at interfaces — scientifically between different disciplines and ap­ tant systems that are specifically fo­ New capacity has come on stream just fascinating! But surfactant sci­ plications. That is why it is crucial to cused on the customers’ needs. but the trend from commodities to ence is not an end in itself — surfac­ meet and communicate across bor­

10 CHEManager | Fine & Specialty Chemicals M a r k e t s & C o m pa n i e s

ders! The CESIO­ 2019 congress wants Talking about the hot topics in citing business opportunities. Bio- or even chemicals, but rather come in to demonstrate that there is an ongo­ surfactants R&D, an important over­ surfactants are already mentioned the way we develop and manufacture ing process in our industry to better riding theme is the deeper under­ as an important area where there is our products. Think of the lightning- understand the application conditions standing of complex mixtures of sur­ a lot of activity both on the products fast development we now see in fields of the future surfactant value chain. factants and other components like themselves and on biochemical pro­ like artificial intelligence and compu­ polymers, enzymes and small partic­ duction routes. ting power. We are at the verge of a les. These advanced formulations are Maybe the next innovation leap Challenges Open Up scientifically fascinating and offer ex­ will not be a new class of surfactants Continued Page 12  New Opportunities

The more complex the product for­ mulation, the more surfactants are needed as key ingredients that help to combine substances, which other­ Visit us at CPhI North America Booth 1130 wise would be incompatible or ad­ versely affect the components’ value. In the field of household detergents, our customers have been quite suc­ cessful in substituting chemicals in their formulations by enzymes. Many producers of surfactants have started to test and develop systems that contain surfactants together with enzymes. In other applications, customers are looking for proces­ ses and formulations that are more energy-efficient and need less re­ sources overall, like crop protection requiring less active ingredients to let ’s co achieve the same result or recycling road surfaces to save on energy and create natural resources. These challenges demand better insight into the inter­ action of surfactants and other in­ gredients, and this in turn opens up new opportunities.

Hot Topics in Surfactants Innovation

There is a multitude of drivers of surfactant innovation as surfactants are used in many applications, each with their own specific drivers. Try­ Metathesis does it better, ing to generalize a bit, there are a few clear trends: eco-friendly solu­ Umicore does it best tions and bio-based products is an Our metathesis catalysts deliver highly selective carbon-carbon bonds, important trend although surfactants with high yields and minimal waste, for more precise and efficient reactions. We support your metathesis needs from research through to commercial scale, have been made from bio-based raw offering the very best in R&D, IP security, global manufacturing and security materials for many years. Related of supply. We will continue to focus on innovation to allow you to develop more efficient, cost-effective and sustainable chemistry. drivers are sharper regulations and Let’s co-create to make a difference pmc.umicore.com voluntary certifications like eco-la­ l bels, providing clarity and confidence to downstream users in a variety of markets, including cleaning, perso­ nal care, asphalt and agrochemicals. Also important are solutions that al­ low users to use less resources, be it material or energy. Examples include low-temperature cleaning, laundry technology with reduced water use and more energy-efficient indus­ trial processes. To capitalize on these trends, surfactant suppliers will need a thorough understanding of their target applications as well as the abi­ lity to innovate in collaboration with customers and technology providers.

CHEManager | Fine & Specialty Chemicals 11 M a r k e t s & C o m pa n i e s

revolution, which is likely to trans­ example is oils & fats; while surfac­ tainable. Scientists, regulators and novel surfactants with unique pro­ form every field of industry, including tant production is a relatively small industry stakeholders are trying to perties. chemicals, and of course surfactants. use compared to food or bio-fuels it determine what is truly sustainable Surfactants are fascinating ma­ is still critically important for our in­ — clearly a challenging situation. terials with their affinity to inter­ dustry to establish a sustainable sup­ Having said that, new raw mate­ faces, tendency to form aggregates Sustainability is More than a ply chain of natural oils like palm, rials bring a lot of new opportuni­ and interaction with other ingre­ Buzz Word coco and soy. ties and it is not just about oils and dients. This also means that they are If we look at the product side the fats. ­The emerging bio-economy is challenging to handle and “standard Sustainability is critically important public debate, or “buzz” probably has testing” for regulatory purposes can to the whole industry. Until now the most direct impact on value chains even be misleading. An important surfactant industry has mainly fo­ ending up in private consumption like aspect of our industry organization, cused on the ecological aspect, we home- and personal care although in­ “We develop new business CESIO, is to provide knowledge and use renewable raw materials, deve­ dustrial users are also looking for sus­ models that are not ensure that regulations are develo­ lop more biodegradable products etc. tainable solutions. A key here is com­ necessarily based on ped based on facts, science and cor­ Sustainability has two other impor­ munication along the value chain. growing volumes, but on rect testing. tant pillars though, and it is becoming Many consumers are increasingly loo­ more and more clear that the chal­ king at the origin of products, requi­ higher effectiveness and lenges we are facing involve all three ring transparency from suppliers and quality.” Staffan Asplund, RD&I director Sur­ pillars; ecological, social and econo­ development of reliable and manage­ face Chemistry, Nouryon, Stenungs­ mic aspects. able certification standards for e.g. und, Sweden; president, CESIO Exe­ If we look at raw material sour­ fair trade and eco-labels. cutive Committee cing it is obvious to strive for rene­ Natural raw materials are already providing building blocks with new wable sources but this only works if used, and their importance will in­ functionality and a different pricing the supply chain of the needed bio­ crease further. As just discussed logic than traditional chemicals. We [email protected] materials come with sustainable so­ though, “bio-based” is not sufficient also see new synthesis opportunities www.cesio.eu cial and economic conditions. A clear to make a raw material source sus­ and altogether this opens paths to www.cesio-congress.eu FINE & SPECIALTY CHEMICALS APRIL DISTRIBUTION & LOGISTICS MAY PHARMA & BIOTECH SEPTEMBER REGIONS & GUIDE LOCATIONS DECEMBER © BillionPhotos.com - Fotolia

Special Focus Issues CHEManager.com Your Business 2019 in the Spotlight Editorial Sales Dr. Michael Reubold Dr. Ralf Kempf Thorsten Kritzer Jan Kaeppler Publishing Manager Managing Editor Advertising Sales Manager Media Consultant Tel.: +49 (0) 6201 606 745 Tel.: +49 (0) 6201 606 755 Tel.: +49 (0) 6201 606 730 Tel.: +49 (0) 6201 606 522 [email protected] [email protected] [email protected] [email protected]

12 CHEManager | Fine & Specialty Chemicals M a r k e t s & C o m pa n i e s

The R&D Footprint of the Chemical Industry Chemical R&D Spending Generates Long-Term Benefits for Society at Large

A new ICCA report based on ment of new technology, processes, social benefits. While the industry’s sults, societal benefits by far out­ a study by Oxford Economics and products that enhance efficiency R&D efforts are obviously aimed at weigh the private financial returns and productivity, and can have wider commercialization of research re­ from innovation. (mr) acknowledges the chemical in- dustry as a crucial contributor to the world’s Gross Domestic Product (GDP).

According to the report titled “The Global Chemical Industry: Catalyzing Growth and Addressing Our World’s Sustainability Challenges” the sec­ tor is making an estimated $5.7 tril­ Global Added Highly lion contribution to the global GDP through direct, indirect and indu­ network value focused ced impacts, equivalent to 7% of the world’s GDP, and supporting 120 mil­ lion jobs worldwide. Directly, the chemical industry ad­ ded $1.1 trillion to world GDP and employed 15 million people, making it the fifth-largest global manufactu­ ring sector. For every dollar genera­ ted by the chemical industry, a further 4.20 dollars is generated elsewhere in the global economy. Companies in the chemical industry spent an estima­ ted $3 trillion with their suppliers in 2017, buying goods and services used in the manufacture of their products. This supply chain spending contribu­ ted an estimated $2.6 trillion to global GDP and supported 60 million jobs. In addition, in 2017 the global che­ mical industry invested an estimated $51 billion in Research & Develop­ ment (R&D), supporting 1.7 million Drug Drug jobs and $92 billion in economic ac­ tivity. China was home to the largest Substances Products chemical R&D spend, with an invest­ ment of $14.6 billion, followed by the US and Japan, with a $12.1 and a Siegfried offers full-fledged integration of Drug area of Drug Product, we create value by offering $6.9 billion investment, respectively. Substance and Drug Product development and sophisticated solid oral dosage and complex sterile Oxford Economics calculates that manufacturing services in one business model formulation development and manufacturing this R&D spending supported 1.7 mil­ to support our customers’ entire value chain expertise. lion jobs and $92 billion in economic from chemical development to commercial activity. Furthermore, the innovations that emerge from such R&D activity in­ production. Our foundation is built on inherited Siegfried has 9 sites worldwide with chemical variably offer “spillover” benefits that technical know-how and expertise. Our culture is manufacturing multi-purpose cGMP locations in spread far wider than the chemical built on loyalty, respect, credibility, sustainability Zofingen and Evionnaz (CH), Pennsville (US), sector itself, raising productivity levels and compliance. Nantong (CN), Minden (GER) and St. Vulbas (FR). across the global economy. The chemi­ Our Drug Product manufacturing sites are located cal industry’s innovation and R&D acti­ In the field of Drug Substance, we work closely in Zofingen (CH), Malta, Hameln (GER) and Irvine vities often lead to the development of with our customers to develop innovative chemical (US). new products and processes. processes adding more benefit and value. In the R&D spending generates long- term benefits for society at large. The www.siegfried.ch chemical sector’s research boosts the global economy through the develop­

CHEManager | Fine & Specialty Chemicals 13 S t r at e g y & M a n ag e m e n t

The Need for Innovation in Pharmaceutical Manufacturing Single-Use Technologies and IIoT Solutions in Biopharmaceuticals Manufacturing

The global pharmaceutical industry is evolving with the rising need ble components. Key products consist optive T-Cell (CAR-T) market with both for novel therapies in the changing disease landscape. As a result of of single use mixers, bag assemblers, Novartis and Gilead. In addition, there disposable aseptic connectors, pre- are over 400 cell and gene therapies rising prevalence of chronic infectious diseases as well as growing packed chromatography columns etc. (C>) in preclinical to phase III de­ cancer incidence, market needs are shifting from traditional small The single use/disposable biore­ velopment, and approximately 1,700 actors enable multi-product flexible clinical studies are underway globally. molecules (chemicals) to large molecules (biologics). The five big manufacturing, easy transfer of ope­ Despite the large market oppor­ themes that are currently being observed in the bio-pharma manu- rations, fast changeover, busy facili­ tunity, issues with product variability ties and lean operations. Therefore, and a deficit in large-scale C&G the­ facturing market are highlighted in figure 1. we are witnessing a shift to flexible, rapy manufacturing capability ra­ small-volume manufacturing compri­ main, with reported waiting time of sing of single-use systems with bio- 1.25 years before the commencement However, biopharmaceutical proces­ facturing processes. Disposable tech­ analytical capabilities, and exploring of manufacturing. Additionally, autolo­ sing involves unique complexities nologies for downstream processes continuous processing technologies gous therapies require special hand­ in the overall process such as long are making rapid advances, e.g. dis­ in modular facilities. ling under very stringent temperature running batches, batch automation posable, pre-packed chromatography requirements. They are also typically and product quality which cannot be columns. These provide seamless and time sensitive and must be delivered measured in real-time. To address the scalable implementation to upstream Decentralized Manufacturing within clearly agreed time frames. issues related to biopharma manu­ and downstream operations in bio­ Biopharma companies will increas­ facturing, companies opt for different pharmaceutical manufacturing. About 40% of the total growth in the ingly need to decentralize and out­ types of manufacturing techniques Disposable production methods pharma market will be attributed to source manufacturing of low volume- to avoid batch contamination and in are generally used for lower volume oncology, cell and gene therapy, rare turn maintain product quality, lea­ manufacturing for clinical and com­ diseases, and neurosciences. Two ding to the adaptive manufacturing of mercial requirements. The disposable multibillion-dollar biotechnology deals „The requirement for the biopharmaceuticals. technology does not involve processes have already been announced in the commercial-scale cell and Single use and modular techno­ such as cleaning and sterilization of new year resulting in the busy start to logy along with a continuous proces­ the bioreactor and hence saves time global deal making. Namely, Eli Lilly gene therapy manufacturing sing approach is not only modernizing and reduces stress on the manufac­ agreed to buy Loxo Oncology for about will propel growth in single- the industry but also minimizing the turing staff. The capital expenditure $8 billion and Bristol-Myers Squibb’s use technology adoption.“ risks associated with making chan­ is much lower compared to stainless $74 billion takeover of Celgene. In ges to the existing system. Single use steel bioreactor technologies but in­ early 2018, Celgene had bought Juno Unmesh Lal, Frost & Sullivan bioreactors are being widely used in volves higher variable costs due to for a record $9 billion to boost their upstream biopharmaceutical manu­ the need for replacement of disposa­ cancer pipeline and compete in the ad­ high complexity C> and collaborate with contract development and manu­ facturing organizations (CDMOs) de­ dicated to supporting commerciali­ zation of therapies. As more C> transition from clinical trials to com­ mercial markets, CDMOs will increas­ ingly employ single-use technology (SUT) in entirety or hybrid models to achieve decentralized manufacturing closer to the patient­ and meet challen­ ging supply chain demands. SUT de­ velopers in turn will develop scalable solutions taking into account the chal­ lenges of extractable,­ leachable and reproducibility. While 100% implementation of SUT in upstream processing will re­ duce the total cost of goods sold (COGS) by 15–20%, it will also reduce the initial capital outlay and net in­ vestment cost (clean-in-place, water for injection) by 35–40%. The pro­ portion of SUT to total industry capa­ city is less than 10%, but new instal­ lations for C> manufacturing will witness between 25% and 30% appli­

©cassis - stock.adobe.com cation of SUT. Therefore, Frost & Sul­

14 CHEManager | Fine & Specialty Chemicals Fig. 1: Five big themes for biopharma manufacturing

livan predicts that the requirement technology disposable components, Reduce Costs, for the commercial-scale cell and the Industrial Internet of Things (IIoT), Increase Efficiency gene therapy manufacturing will pro­ smart objects, remote control, and pel growth in single-use technology augmented reality. These techniques The future of biopharma manufactu­ adoption by 22% in 2019. greatly influence design, construction, ring lies in connecting data and pro­ layout, and operation of a plant — and, cesses, involving components of ad­ consequently, the timing and cost of aptive and modular manufacturing IIoT in Manufacturing the overall project while maintaining in a predictive and cognitive plant. regulatory compliance. This shall result in higher quality, ef­ Over the past few years, several fun­ IIoT has the potential to transform ficiency, regulatory compliance and damental changes in the biopharma the pharma industry by offering va­ enable optimization, customization of manufacturing process have occurred. lue propositions such as faster time to processes and collaboration between By leveraging right first time and ma­ market, and cost optimization, thereby all stakeholders involved in the ma­ nufacturing 4.0 principles, the indus­ ensuring higher productivity. nufacturing value chain. Additionally, try is looking to improve manufactu­ IIoT also permits smart there shall be a reduction in time to ring efficiency, quality by design and warehousing and routing of products market for biologics, errors due to compliance. Revolutionary disruption along with predictive maintenance process variability and associated powered by an incredible shift in tech­ of machine and equipment. Benefits costs, thereby giving manufacturers nologies is impacting many industries include lowered costs, reduction in the competitive edge to stay on the that will drive transformation in bio- waste production and real-time visual growth trajectory. manufacturing. As depicted in figure 2, feedback, thereby improving operatio­ With the changing market land­ all of these changes are creating a pa­ nal efficiency. IIoT is expected to find scape, CDMOs are adopting advan­ radigm shift in pharmaceutical manu­ application in end-to-end digital inte­ ced manufacturing technologies such facturing to more predictive and ad­ gration across the manufacturing and as single-use/disposable bioreactors, aptive facilities that leverage modular drug delivery value chains. continuous, modular POD manufactu­ ring, and so on with the integration of IT-based solutions implementing IIoT by means of strategic collaborations and partnerships. Larger participants are resorting to mergers and acquisi­ tions (M&As) in order to gain specific therapeutic and technical expertise from smaller, niche Bio-CDMOs. As a result, CDMOs are shifting toward providing value-added services by es­ tablishing themselves as a one-stop- shop for their pharma clients.

Unmesh Lal, program manager, Transformational Health, Frost & Sullivan

Fig. 2: Role of technology in biopharma manufacturing: innovating to zero to [email protected] make manufacturing error free. www.frost.com

BSC_Ad_Fine_and_Speciality_Chemicals_50x303mm_E03.indd21.03.2019 1 16:17:08 S t r at e g y & M a n ag e m e n t

Biosimilars: The Price Challenge Market Prices Have Come Down Significantly — How Much Can Copycat Makers Really Earn?

Biosimilars are conquering the pharmaceutical market, the produ- 73% price decline in the 3.75 years if they really can make as much mo­ cers of biopharmaceutical follow-on drugs are competing for reve- since launch of biosimilars in major ney as they have expected? In contrast markets. Prices in the Enbrel (etaner­ to generic drugs the development of nues and market shares. With the launch of copycats for Humira cept) market fell by 45% in just 2.75 a biosimilar requires significant time, in late 2018 prices fell fast and sharply. Now biosimilar companies years since biosimilar launch. knowledge and investment. Other than With adalimumab the race of the classical generics, which have a sim­ might wonder if their business models really pay off. biosimilars has definitely taken off ple molecule structure, biosimilars­ with high speed. Currently more than are made of living cells and have a 50 biosimilars are being marketed in complex architecture. While generic It has been a far-reaching experi­ gevita. A few days later the company Europe, 17 in the US. Health care data companies usually spend some few ence for the pharmaceutical indus­ raised the discount up to 39% compa­ specialist Insight Health reports that millions of euros for development, bio­ try: In October 2018 the patent of red to Abbvie´s reference drug. biosimilar prescriptions in Germany similar companies have to invest up the world´s best-selling drug Humira nearly doubled in 2018 from 0.7 mil­ to €150 million for each product. Al­ (adalimumab) expired in the Euro­ lion to 1.3 million. Although the over­ though biosimilar companies can com­ pean Union. Abbvie, the company who Discounts up to 80% all level is still low, the earnings are in 2017 made revenues of $18.4 bil­ significant. The rise of the biosimilars lion with the rheumatoid arthritis Abbvie’s CEO, Rick Gonzalez, noted is good for the health care systems product, immediately was confronted in late October 2018, that biosimilar which can save millions — if not billi­ “If prices would drop further with a wave of biosimilar competitors versions were available at discounts ons — of euros and dollars. Warwick biosimilar companies could — copycats of the biopharmaceutical ranging from 10–80%. “The discoun­ Smith, director general of the British medicine. ting has been on the higher end,” said Biosimilars Association (BBA), said in have difficulties to cover Sandoz launched its biosimilar Hy­ Gonzalez. This went in line with the an interview that in the UK — due to their costs.“ rimoz, Biogen came up with Imraldi, German lobby organization Pro Bio­ biosimilars — in some indications one Amgen with Amgevita and Mylan similar who expected the competition third more people are being treated with Hulio. All of them competed hard “to be intense because of the large at half the previous cost. on prices: Just a few days after mar­ number of competitors launching at pensate lower prices to a certain de­ ket launch of its biosimilar, Sandoz the same time.” gree by a wider range of patients they doubled the price discount for Hyri­ A significant price erosion can also How Much Can reach with their products, the core moz. After an original price reduc­ be seen with other biosimilars. Ronny They Really Earn? question remains: How far can they go tion of 21% it then offered a rebate Gal, analyst of New York investment down with their prices until the busi­ of up to 40%. Amgen initially had an­ company Bernstein, says that the Re­ Meanwhile developers and manufac­ ness doesn´t make sense anymore? nounced a reduction of 18% for Am­ micade (infliximab) market saw a turers in this industry ask them­selves Carsten Brockmeyer, CEO of the Munich, Germany-based biosimilar developer Formycon usually commu­ nicates that he expects biosimilar pri­ ces 15–20% below originators costs at the beginning of the biosimilar mar­ keting phase. In the further course biosimilar companies calculate that prices might drop up to 30– 50%. The business models are being built on these assumptions. If prices would drop further biosimilar companies could have difficulties to cover their costs for 7–8 years of research and development, for clinical studies, for the application process of their drugs and the marketing costs. There are others threats too, es­ pecially for small and mid-sized bio­ similar companies with limited fi­ nancial possibilities. The biosimilar industry often emphasizes that pro­ ducers of originator drugs will mostly withdraw from the market once bio­ similars have come up. The copycat representatives argue that the re­ tracted manufacturing processes of the original biological drug makers are based on standards that existed

© Abbvie 15 or 20 years ago. Today biosimilar

16 CHEManager | Fine & Specialty Chemicals S t r at e g y & M a n ag e m e n t

list price after biosimilar entry. If the tion: How many companies are wil­ Supply share of adalimumab biosimilars in price of the reference product gets ling to take such a risk pricing their counting units on total Adalimumab market under pressure the prices for biosimi­ biosimilars with massive discounts [%, excl. parallel imports] lars might be forced to fall further to garner a high market share?” And down as well. Warwick Smith, the British BBA di­ 30% rector, warned that “if you get a race

28,0 to the bottom … that is not a sustain­ Profitability able market.” 23,8 While biosimilar companies face 20% to Be Questioned the whole cost-related risks of deve­ 19,5 19,9 Hamzah Aideed, a senior business in­ lopment and marketing one group 14,1 sights analyst who joined the World in this industry finds itself in a more 13,2 Supply Share [%] 10% Biosimilars Congress USA in May comfortable position. Contract de­ 2018, pointed out that some presen­ velopment and manufacturing or­ ters questioned whether the 30–40% ganizations (CDMOs) as Lonza, Ca­ 4,8 net discount, which is commonly re­ talent, Patheon, and Alcami position 0% 1,7 CW 42 CW 43 CW 44 CW 45 CW 46 CW 47 CW 48 CW 49 ferenced as a likely price threshold themselves as specialists for bio­ 2018 2018 2018 2018 2018 2018 2018 2018 for biosimilars, was even sustainable pharmaceuticals. In recent years

Source: AG Pro Biosimilars, INSIGHT Health NPI Weekly in for biosimilars companies in the long such companies also have used ac­ counting units (syringes and pens) © Abbvie run. Discounts as high as 70% less quisitions to build end-to-to end ser­ than the reference brand were propo­ vice models that provide both active Further increasing acceptance and intense competition for Adalimumab biosimi- sed in order for biosimilar companies pharmaceutical ingredient and drug- lars: Just 8 weeks after market entry, the supply share (Biogen/Samsung Bioepis to gain meaningful market shares, he product development and manufac­ — Imraldi, Mylan — Hulio, Hexal/Sandoz — Hyrimoz, Amgen — Angevita) is wrote on a platform called decision­ turing. Their advantage: They don´t already just under 30%. resourcesgroup. “If they gain signifi­ have to negotiate market prices. cant profitability at this level can be severely questioned”, argued Aideed. companies with their latest produc­ of biosimilar competitors. But even “Hearing data like this begs the ques­ Thorsten Schüller, CHEManager tion processes have much lower costs with other biopharmaceuticals run­ than the “old” pharma industry. ning out of patent there is mostly more The Humira case demonstrates than just one biosimilar company try­ that things can evolve differently. Abb­ ing to get a piece of the cake. Formy­ vie dropped prices for its adalimumab con for example points out, that it is by 80% in some European countries clearly ahead of others with the deve­ as several media and analysts repor­ lopment of its Lucentis (ranibizumab) ted. If this were true — Abbvie didn´t biosimilar. Clinical phase III has been comment on this — such a price would completed, market entry in the USA be a clear declaration of war on bio­ is planned for 2020. On the other side similar producers. Under such cir­ Korean Samsung Bioepis has also be­ cumstances many companies will gan a phase III study in April 2018 for be forced to scrap their calculations. its ranibizumab biosimilar. Some market experts mention that Today Samsung Bioepis, which there is indeed no real reason why ori­ was newly established just in 2012, has already four biosimilars ap­ proved and marketed across Eu­ rope. It has gained more than 60% “[Some] CDMOs position of the adalimumab market in Ger­ many with its Humira biosimilar. In themselves as specialists for 2018 the company’s accumulated sa­ biopharmaceuticals.” les for three of its biosimilars in Eu­ rope reached $545.2 million. Further­ more, the company recently signed a joint venture with C-Bridge Capital ginator companies shouldn´t go down to develop and commercialize next- Andrei Merkulov - Fotolia.com stock.adobe.com © guteksk7 | with their prices in order to stay in the generation biosimilars in China. In market. As they had the market for this way, Samsung Bioepis paves the their products to themselves for many way to enter one of the biggest phar­ years, their investments generally maceutical markets in the world. The have been written off. No further sig­ agreement covers Samsung Bioepis’ nificant investments are necessary, so third-wave biosimilar candidates to they just could let the production run Lucentis and Soliris, respectively. With as they did all the years before. this track record in mind competitors www.chemanager.com shouldn´t underestimate the Koreans. The pricing model of biosimilar Information is Key! Samsung Bioepis: companies may be questioned even the Korean Force from another point of view. Many Eu­ B2B Portal and Business Newspaper ropean nations have implemented for executives in the chemical and pharmaceutical industry Some may argue that adalimumab is policies that require a mandatory re­ a special case due to the high number duction of the reference product’s

CHEManager | Fine & Specialty Chemicals 17 T e c h n o lo g y & I n n o vat i o n

Cheaper, Faster, Smaller, Cleaner Prospects of Flow Chemistry for Fine & Specialty Chemicals and Pharma

Developed and technically proven around 1995, micro reaction tion’’. It may sound like catch phra­ of millimeter-scale equipment, and technology was probably highly overestimated for the first 10 years ses, but the ‘’cheaper, smaller, clea­ further upscaling is done with num­ ner’’ and ‘’making more with less” bering up. and underestimated for the next 10 years. Meanwhile it is on its way has been proven in different applica­ to an established process technology, not only in research and la- tions — not only in research and la­ boratory, but also in large scale pro­ MRT in Research and Labs boratory, but also in large scale production. duction. This makes MRT today more interesting than ever before, not only In Brazil, the Technology Center for for economic reasons but also for sus­ the Chemical and Textile Industries In flow chemistry, a chemical reac­ Especially with respect to rapid, tainable development. of the National Industrial Training tion is run in a continuously flowing highly exothermic, explosive or toxic In terms of “time to market” — in Service (SENAI), located in the state stream in contrast to batch produc­ reactions, whose safety risks make pharmaceutical and fine chemical in­ of Rio de Janeiro, is an organization tion. The subfield of micro process batch reactor use very challenging or dustries of special importance — it is which focuses on education and tech­ engineering, that deals with the de­ even impossible, the characteristics noteworthy to point out that the scale nological innovation for process in­ sign of micro-structured reactors for of continuous flow micro and milli re­ up from laboratory to production can dustries. One of the main activities chemical reactions, is also known as actors offer clear benefits. be carried out more simply com­pared of this center is to offer research-ap­ micro reaction technology. plied services to innovate in proces­ ses and products for the chemical in­ The technical advantages of conti­ dustry. SENAI Innovation Institute nuous operation in micro- and milli “Our Miprowa technology (ISI) for Biosynthetics (one of the cen­ reactors compared to batch reactors offers a time-efficient and ter divisions) for example will have a include: integrated scale-up based on pilot scale unit that, for some sectors ¨¨Ultra-fast mixing established equipment concepts.” of the chemical industries, like paper ¨¨Highly efficient heat transfer or petrol, can be used for investiga­ ¨¨Short and defined residence times Anne Kaaden, key account manager, Ehrfeld Mikrotechnik tion and design of an industrial scale ¨¨Simple process control due to low unit. Other clients who aim at bigger system inertia productions are asking to estimate ¨¨High operational reliability due to The economic advantages of micro to other established technologies. The industrial scale costs and setting minimum hold-up reaction technology (MRT) compared characteristic performance features technical targets for process develop­ ¨¨Improved safety to batch technology can be described of micrometer-scale laboratory ap­ ment. Joao Bruno Valentim from ISI ¨¨Short development times with the term ‘’process intensifica­ paratus correspond widely to those Biosynthetics is convinced of a huge potential for flow chemistry in the chemical industry. Once they prove it works technically, it is a matter of matching the expectations of cost re­ duction and reducing the impact of scale on chemical plants projects. At the University of Graz in Aust­ ria, Oliver Kappe is professor of chem­ istry and scientific director of the Cen­ ter for Continuous Flow Synthesis and Processing (CC FLOW) at the Research Center Pharmaceutical Engineering (RCPE). CC FLOW as an academic lab cannot provide commercial scale ma­ nufacturing but search for novel flow chemistry routes to molecules of in­ terest. Kappe sees a lot of interest in flow chemistry both from the acade­ mic world but also in pharma and other industries. He is convinced that, given the enhanced safety and ex­ panded process windows, there is so much you can do in flow that you can­ not do in batch. The vision obviously is not that all batch chemistry will be replaced by flow, but in future there will be many more safe, reliable, and automated flow processes available to practitioners interested in both lab

©evannovostro - stock.adobe.com ©evannovostro and commercial scale.

18 CHEManager | Fine & Specialty Chemicals T e c h n o lo g y & I n n o vat i o n © Ehrfeld Mikrotechnik Rectangular channels for optimized heat transfer in a Miprowa reactor.

In Australia, the Commonwealth Milli Reactors in Scientific and Industrial Research Or­ Production Scale ganization (CSIRO), which is the na­ tional research organization, has a Shaoxing Eastlake High-Tech is an mandate to assist the Australian che­ agrochemical producer founded in mical industry. Using the latest in flow China near Shanghai in 1990, which

chemistry and process technology, not only serves the Chinese market, © Ehrfeld Mikrotechnik CSIRO can provide manufacturing but also exports its products to more Integration of the continuously running Miprowa flow reactors into the existing solutions to rapidly synthesize small than 20 countries, including the US building infrastructure at Shaoxing Eastlake in China. molecules and polymeric materials. and EU. The company provides active Christian Hornung of CSIRO says that ingredients to the global agrochemi­ tures on a production scale and was sible reference for micro reaction many of their industrial customers cal market segment. designed for a highly exothermic alk­ technology in production applica­ plan to take their synthesis route into In 2016, Shaoxing Eastlake com­ oxylation reaction. The reactor has a tions. production using continuous proces­ missioned a milli reactor which was nominal width of 400 mm and a length sing. With the new FloWorks facility designed, manufactured and sup­ of 7 m and contains about 150 rectan­ Volker Oestreich, opening its doors at CSIRO Clayton plied by Ehrfeld Mikrotechnik in Wen­ gular reaction channels with exchan­ CHEManager early in 2019, they will continue to be delsheim, Germany. The decision for geable static mixers. It replaced more a center of excellence in flow chem­ their Miprowa technology was driven than 20 batch reactors while doubling istry working with Australian and in­ by achievable product quality, signifi­ the original capacity. Executives and industry experts ternational chemical manufacturers. cantly improved yield, safety aspects In November 2018, Eastlake star­ dealing with flow chemistry share He believes the new facility will help and a short return on investment, says ted implementing two additional their insights on the current status extend their offer to improve che­ Anne Kaaden, key account manager milli reactors of same size, thus trip­ and future potential of this techno­ mical manufacturing processes for at Ehrfeld. The continuously opera­ ling their production capacity at its logy. Read their statements on the companies that have not adopted or ted production reactor with a capacity Shaoxing site up to 30,000 t/y. These following pages. heard of flow chemistry yet. of up to 10,000 t/y is using millistruc­ three production reactors are a vi­

First in flow Award-winning flow chemistry systems SYRRIS.COM

CHEManager | Fine & Specialty Chemicals 19 T e c h n o lo g y & I n n o vat i o n

Flow Chemistry: Key Technology for Sustainable Processes Experts Discuss Challenges and Opportunities of Micro Reaction Technologies

You can call it flow chemistry or micro reaction technology (MRT) Transforming process engineering pro­ perts dealing with flow chemistry to — both terms describe a technology with enormous advantages for duction from the batch principle to con­ share their opinion on the current tinuous flow processes based on micro status and future potential of this many process engineering applications. It replaces discontinuous and milli reactors may not always be technology. We wanted to know: batch processes with a continuous method in which reactions take so easy for production staff to accept — ¨¨In your opinion, what are the stron­ despite its advantages. Adopted by the gest drivers (success factors) of the place in extremely miniaturized structures. pharmaceutical industry in recent ye­ implementation of flow chemistry ars, the technology platform offers po­ processes? tential in many respects, but although ¨¨Which barriers are slowing down the technology as such is not at issue it or impede the implementation of experiences acceptance problems. flow chemistry processes? Especially with respect to rapid, ¨¨In which fields do you expect flow explosive, toxic or highly exother­ chemistry to find future applica­ mic reactions, whose safety risks tions in the process industry? make batch reactor use very difficult ¨¨What does it need for flow chem­ or even impossible, the characteris­ istry to be recognized as a breakt­ tics of continuous flow reactors of­ hrough technology? fer clear benefits. Nevertheless, MRT has yet to gain popularity. CHEMana­ Read the insightful answers of the ex­

©yspbqh14 - stock.adobe.com ger asked executives and industry ex­ perts here.

A Technology Whose Use is Indispensable A Boost to Efficiency, Ralf Boehling, senior manager Process Development, Adaptability and Responsiveness Process Screening/Kinetics Lab, BASF Walter Linhart, head of sales and managing partner, The existing market situation has al­ plant is not quick enough and causes Microinnova ready led to a shift in strategy from high development cost. Additionally, it large quantity chemicals to highly in­ takes a long time for construction and The main drivers are the need to be competitive and free up novative specialties. For many building the technical plant. Es­ batch production capacity. Fine and specialty chemicals syntheses you can use pecially for small scale producers are increasing their interest in flow chem­ classical batch vessel. plants the cost is prohi­ istry, as experienced on half of the projects that But if you are handling bitive if building the Micro­innova has worked on. highly toxic, hazar­ plant traditionally on Our expertise is combined with risk assessments at dous substances site step by step. early stages to increase chances of success and or the syntheses This, however, se­ ease the transition to continuous manufacturing. have to run under verely increases Misconception one: Limited type of reactors: Flow high pressure, high the investment risk chemistry can be achieved not only through the use temperature or the for new products of milli and micro reactors, where you have a limitation products are ther­ because the market to mainly fast liquid/liquid reactions with low viscosity, mally unstable, or needs and price but also through the use of other technological alternatives. the syntheses inclu­ structures cannot be These alternatives can be plug flow reactors, static mixers, re­ des a gas phase step, realistically foreseen. action columns, extruders and others. Even other energy sources can be used to you preferably have to work Therefore, to shorten the enhance the benefits of continuous manufacturing, such as ultrasound and micro­ under continuous flow conditions. process development time and to wave. So, for BASF there is a need to open reduce cost and time for building Misconception two: Only batch manufacturing is flexible: The introduction of new these process windows. But one of small scale continuous plants is a pla­ modular plants has combined the benefits of batch manufacturing and flow chem­ the major problems to face is that the titude but of course is the key for new istry. These types of plants offer the flexibility of batch processes, while simultane­ process development for a contin­ innovative processes, reactors and ously being able to work continuously, which gives a big boost to the chemical in­ uous plant from lab to production products. dustry regarding efficiency, adaptability and responsiveness to the market. Disciplines separation: Typically, chemists fix the synthetic route and engineers de­ velop the process, taking over the project at pilot stage. For a successful production implementation of a flow process it has been noticed, that companies who have im­ plemented a continuous processing strategy have started forming interdisciplinary teams for this very reason. Increased Process Performance and Safety Availability of production capacity: Especially in the area of CMOs, there is a serious chicken-egg problem. More and more continuous processes are being developed Olaf Wachsen, head of Group Process Technology, by big pharma companies. It is an increasing market, but production capacities at Group Technology & Innovation, Clariant CMOs are missing. CMOs do not get the projects, because they lack experience and production capacities with continuous processes, and in turn they do not invest It took about two decades after micro and milli reactor tech­ in the technology, because of the missing projects. nology has reached the production scale with significant Flow chemistry is already being applied in the fine chemicals industry, where we production volumes. Now, curiosity and openness of have developed several projects in different areas, like for the production of additi­ chemical­ companies grow significantly to benefit from this ves for lubricants, phenolic resins, acrylate polymers and crosslinking agents, technology’s potentials like access to new and better pro­ a­nionic surfactants, silicone release agents and primer and wax mixtures. ducts, increased process performance and significantly For flow chemistry and continuous manufacturing to penetrate the industry it will re­ better process safety. quire some more patience. However, both academia and industry have increased their interest in and support for this technology.

20 CHEManager | Fine & Specialty Chemicals T e c h n o lo g y & I n n o vat i o n

Further Development Will Increase Confidence Unsurpassed Heat and Mass Transfer Properties Peter Poechlauer, innovation manager Pharma Services, Stefan Brand, head of Process Innovation, Group Technology & Innovation, Patheon Group Process Technology, Clariant

Originators discover new drug candidates by screening sub­ Flow chemistry, based on milli and micro re­ bution of polymers can be much better cont­ stance libraries containing only a few milligrams per sub­ actors, is a powerful production process rolled with flow chemistry than during batch stance. Many synthetic methods employed in library technology with unsurpassed heat and mass processes. The small reactor volume of milli synthesis are not scalable: during further development, transfer properties. It is especially be­ and micro reactors is the reason for in­ they have to be modified or redesigned to deliver neficial for fast chemical reactions herent safe production processes quantities for further testing. At this point, custom de­ and in cases where an effec­ and allows the exploitation of velopment and manufacturing organizations (CDMOs) tive mixing of the reaction new process windows, e.g. such as Patheon offer to perform the respective pro­ medium is required. use of raw materials which cess development and manufacturing tasks. In this Major drivers for the appli­ are not suitable for batch environment, flow chemistry provides various opportu­ cation of flow chemistry reactions. nities, for instance, to scale up even demanding synthe­ are: globally increasing Prerequisites for the imple­ tic steps without the need for a re-design, to control syn­ process safety require­ mentation of flow che­ thesis processes to deliver products with predictable quality ments, the possibility to mistry within a chemical at all required scales while the ultimately required production enter new reaction paths company are an overall in­ scale is still uncertain, to speed up process development through quick screening and the opportunity to pro­ novative mindset as well as of reaction parameters, and to intensify processes, which reduces investment and vari­ duce tailor-made chemical readiness to invest in new pro­ able, e.g. solvent and raw material costs. products, which is known as pro­ duction technologies. Additional Production of many APIs has moved to the East, freeing up conventional cGMP-rated duct-by-process concept. To a large convincing examples of the success­ manufacturing capacity in the West. This hampers decisions to invest in new technology extend, the quality of polymeric compounds ful realization of flow chemistry plants for pro­ developments that tend to reduce the utilization of this manufacturing capacity further. depends on their manufacturing conditions. ducing e.g. specialty chemicals will speed up In response to the growing number of newly developed APIs with a reduced volume per As an example, the molecular weight distri­ the expansion of this promising technology. API the industry will shift towards concepts of manufacturing and quality assurance based on flow processes in flexible modular plants that are quickly reconfigured to sup­ ply the variety of small-volume products in the required quality and on short notice. Further successful implementation of flow chemistry processes in cGMP manufacturing environments will increase confidence in this technology. It will convince manufacturers of APIs to consider developing flow processes or to team up with CDMOs with proven Benefits across Different Industries and Applications experience in this field. Omar Jina, chief commercial officer, Syrris

For discovery groups and academia, it is undoubtedly about the ability to per­ form chemistry that is not possible by traditional techniques; flow chemistry allows the implementation of multistep reactions and incorporation of tech­ A Technology on the Upswing niques such as electrochemistry or photochemistry. In process or scale-up chemistry, the strongest drivers lie more in the ability to seamlessly scale André de Vries, commercial director, reactions, thereby reducing the time and cost of the process. Many com­ Innosyn panies are focusing on scaling processes of a hazardous nature, such as nitration; continuous flow processes that use smaller mixing volumes There are a number of drivers to im­ well-established culture to run while still maintaining the desired scale are a very attractive proposition. plement flow chemistry processes chemical­ processes in such assets. Flow chemistry has come a long way in the last 10 years and is fast becoming over batch operations. In addition, many chemical products an accepted technology in industry, but there are still barriers to overcome. It is Firstly, a very much improved heat are being used in a heavily regulated always very important to start with education; flow chemistry needs to be inclu­ and mass transfer. Millimeter-sized domain, with tight specs, and any ded in undergraduate chemistry courses to provide future chemists and chemical tubular reactors have a much higher change in production process will engineers with the foundations to solve chemistry problems by employing the most sui­ surface-to-volume ratio than batch lead to new validations and alike. To table tool – batch, flow or other techniques — for the application. A lack of commercially availa­ vessels, intensifying heat and mass overcome some of the hurdles Inno­ ble pilot plant/manufacturing scale systems is also a barrier to large scale implementation, requiring transfer dramatically. Highly exo­ syn is using 3D metal printing (selec­ very large custom projects and considerable capital outlay from industry. This is now being thermic reactions can be executed tive laser melting), as method of addressed and we should see technology become much more accessible in the very near future. (almost) isothermally. choice for manufacturing I believe that to become recognized as a breakthrough technology, flow chemistry needs to be Secondly, a safe opera­ the most fit for purpose widely adopted in multiple industries. At present, there is a rapid drive for implementation in the tion of hazardous reactors for flow pharmaceutical and chemical industries. However, the technology can offer fantastic benefits to and unstable re­ chemistry­ proces­ many other industries, including nanotechnology, flavor and fragrances, food and biotechnology. agents. Thanks to sing. This tech­ Academia has played a vital part in the adoption of flow chemistry and there are now numerous a continuous nique gives maxi­ publications showing the benefits of the technology across different industries and applications. operation the mum flexibility to volumes of flow introduce speci­ reactors are typi­ fic features like cally several ma­ static mixer ele­ gnitudes smaller, ments and tem­ and there is no, or perature probe in­ A Visible Reference of Production-scale hardly any, hold-up lets; one can iterate of these unstable com­ designs rapidly to tailor Micro Reaction Technology pounds. to the specific chemistry at Thirdly, the operating window can hand; and is cost-efficient since only Joachim Heck, managing director, be beyond “normal”, especially the metal ending up in the reactor is Ehrfeld Mikrotechnik temperature and pressures, al­ consumed. lowing the safe use of for example We see the use of flow chemistry For us, the barrier of implementing and recognizing thermic re­ toxic gases, previously avoided on processes being applied success­ micro and milli reactors as breakthrough technology action is of large scale. Also superheating of fully, especially in those fields can be taken by production-scale reference projects alkoxylation common low-boiling solvents to where it can make a severe diffe­ we are able to show in China. Ehrfeld Mikrotechnik type. The speed up the reaction kinetics can rence compared to batch proces­ designed, manufactured and supplied three Miprowa company’s deci­ be executed safely. sing. In practice this entails any production reactors to Shaoxing Eastlake High-Tech sion for the Mipro­wa And finally, process monitoring and sort of organometallic chemistry, Co. for a production capacity of now up to 30,000 t/a. technology was driven control is improved with continuous and the safe use of hazardous re­ These Miprowa milli reactors have a throughput of up by achievable product quality, significantly improved processing, leading to a lower level agents and reaction mixtures, en­ to 1 m3/h each with a nominal width of 400 mm and a yield, safety aspects and a short return on invest­ of impurities. abling shortcut routes to special length of 7 m. Meanwhile, the first of these installed ment. Eastlake serves the global agrochemicals mar­ Implementation of flow chemistry chemicals, alternatively produced reactors has been under stable operation since 2016 ket segment based on their production of active in­ processes, however, is hampered by by lengthy routes preventing the without any disturbances. Every reactor contains gredients. The three Miprowa production reactors are the already widely available batch use of those hazardous com­ about 150 rectangular reaction channels with ex­ a visible reference of the micro reaction technology in vessels of all kind of sizes and a pounds. changeable static mixers. The fast and strong exo­ production scale.

CHEManager | Fine & Specialty Chemicals 21 T e c h n o lo g y / I n n o vat i o n

Unique Opportunity for Innovation and Improvement A Holistic System Approach Luigi Vaccaro, professor, Laboratory of Green Synthetic Organic Chemistry, Andreas Haubrich, head Process Engineering Laboratory, Dipartimento di Chimica, Biologia e Biotecnologie, Università di Perugia deputy head Process Engineering, Sanofi-Aventis

Both academic and industrial research is at­ Flow chemistry is able to improve the effi­ Flow processes have to be handled as a holi­ The entire processing sequence, conside­ tracted by solid opportunities to create inno­ ciency of processes allowing the manipulation stic system approach. Diverse applications of ring reaction, quenching, work-up, extrac­ vation while improving the competitiveness of of unsafe toxic intermediates and reagents flow chemistry in pharmaceutical environ­ tion and purification etc. as part of the holi­ the chemical production. At this concern, flow and offering a unique opportunity to design ment demonstrate the value of this strategy stic design of the preparative route needs to chemistry­ has become a pivotal key innovative protocols for the preparation towards every aspect ranging from syn­ be worked out differently. The ability enabling technology that offers the and manipulation of fine chemicals thesis, in-line analysis and purifi­ to install real-time monitoring unique opportunity to both in­ and active pharmaceutical in­ cation to final formulation and leads to rapid identification novate and improve the effici­ gredients. Flow chemistry will tableting. current process status and/ ency of synthetic methodo­ consolidate its role in this Introducing such a way of or upcoming of trends/is­ logies leading to custo- arena but also find novel thinking early into a deve­ sues. Furthermore, the mized effective processes. opportunities in emerging lopment pipeline can give use of direct in-line purifi­ Therefore, flow chemistry areas of research as, for significant simplification cation and analytical is a successful tool for re­ example, in the manipula­ during the scale up. The techniques can be imple­ searchers to disclose tion of biobased chemicals increasing demand of ma­ mented, thus generating highly relevant publications and in biomass valorization terial needed for the diffe­ a more streamlined and in­ and/or patents while crea­ where academia and indus­ rent stages of development formation enriched reaction ting new opportunities to excel try are both looking for cost- phases can be reached effici­ sequence. in both academia and industry. effective access to a new gene­ ently and finally the building of a As flow chemistry is not a plug While the cost of flow equipment is ration of safe chemicals that can be large-scale facility is straight for­ and play technology a thoroughly often mentioned at this concern, in my opin­ produced in larger scale. ward. process analysis, including each unit opera­ ion this is not the real barrier that prevents Real case applications can confirm the wide Focusing the continuous flow approach to a tion of a process, has to be performed to flow chemistry to establish itself. I consider general utility of this technology and therefore late stage process or a large-scale manufac­ identify e.g. key cost driver’s and most chal­ more important the cultural barrier consisting further research in several different directions turing plant limits the opportunity signifi­ lenging obstacles. in the lack of knowledge about the general is crucial. To achieve this result multidiscipli­ cantly. At these stages stringent timelines of­ All this makes the interaction of different wor­ utility of this technology. I believe that a new nary international consortia of universities ten limit the opportunity to optimize the king disciplines – chemists, engineers, ana­ generation of professionals needs to be trai­ and companies should be created to train specific reaction process and to apply flow in lysts, statisticians and many more necessary, ned to master flow chemistry and eventually next generation of professionals and apply a strategically impactful way. in order to end in an overall economic benefi­ consider it as a common effective laboratory flow chemistry principles in several different In order to step in continuous flow earlier cial process design. By installing interdisci­ tool. Universities and companies will have to areas as green/sustainable chemistry, there is a need for cultural changes due to plinary working teams this flow chemistry will cooperate at this aim via specific industrial pharma­ceutical chemistry, materials for lack of training or education in this area. be able to capture full benefits. Master and PhD programs. energy and fuels.

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Masha Ibeschitz, world-class reflection guide and coach, shows executives and entrepreneurs how they can sustainably increase their business success through personnel development. Your informative and entertaining guide is a must for anyone interested in employee development in the VUCA world.

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22 CHEManager | Fine & Specialty Chemicals T e c h n o lo g y / I n n o vat i o n

Chemical Sales Going Digital: What to Expect? Are the New Digital and Global Opportunities in Chemicals more Threat or Possibility?

Chemicals and digitalization are everywhere in our daily life, whe- ing business on the platform since ther we pay attention or not. By coming up with creative ways of in- their contact information is avail­ able for both parties. The threat of novation, industry professionals can take their business to the next digitalization is often seen when it level. Independent B2B platform Pinpools has taken advantage of comes to privacy and security issues. This emphasizes the need for each this possibility and offers a digital solution for chemical sales. company’s mindset to be focused on Alexander strengthening the key areas such as Lakemeyer, cyber security, regulatory and policy Pinpools issues. The two factors, fresh mind­ set and stronger key areas, are go­ ing to help by using advanced tech­ hot topic when talking about new di­ nology, e.g. cloud services and big gital devices or platforms. This requi­ data analytics. They are also go­ res a company to carefully protect its ing to improve continuous develop­ information and data online. ment of data management, process The fact that Germany’s Fede­ optimization, innovation, and better ral Cartel Office launched an inves­ supply chain management. tigation on Amazon due to possible prob­lems with data security shows that even global leaders are strugg­ Continuous Analysis ling with these challenges. Pinpools, of Global Industry Trends functioning as a digital B2B market­ place, values the privacy of its cus­ There is no doubt that the tomers and ensures that the data is purchasing power is going to shift safe on the platform. The trust fac­ more and more from global lea­ tor provided by the platform is the

©vegefox.com - stock.adobe.com ders to customers, which is the rea­ transparency that allows buyer and son why chem­ical companies need supplier to see each other’s infor­ According to CEFIC, the European ness, they expect to receive the same to analyze ongoing trends affec­ mation when doing business on the Chemical Industry Council, the chem­ fast and smart solutions also as cus­ ting to the customers’ behavior and platform. ical industry is one of the largest sec­ tomers. However, so far, the indus­ the way they make decisions. These tors at global level, and it is going to try has been slowly adapting­ to the trends define what strategies com­ increase even more. The estimate for changes, so transformation to chem­ panies should put into action to se­ Think Outside the Box the worldwide chemical market is to ical digitalization is not going to hap­ cure business growth. reach €6.9 trillion by 2030. Globali­ pen quickly. Chem­ical companies need to wake up zation is definitely going to be a key Digitalization is a real thing: Ro­ to do business faster and more effi­ factor for companies’ success sto­ land Berger and Google Deutschland Smart Solutions ciently and thus save time and mo­ ries because digital solutions enable suggest in a study that 60% of almost ney. There are many possibilities, them to expand the business from 3,000 B2B sales managers think that Making smarter decisions and com­ but it takes to have a fresh mind­ the domestic market to the interna­ digitalization is a critical success fac­ ing up with better solutions is going set and innovative approaches, and tional level. tor. Since it is considered an impor­ to help with innovation. Cost effective to think outside the box. While there For most people working in the tant part for the business, actions practices help companies to invest are ­threats such as data security, it is chemical industry, the shift to the towards digitalization need to be im­ money in the right places which can up to people to decide whether they use of digital channels might sound plemented in order to survive and be achieved by pre-management and feel that these threats outweigh the too much of a challenge but it should succeed in the global competition. better planning process. benefits. One thing is for sure: To se­ be taken as an opportunity. The so- Using the B2B marketplace can cure the growth and success of busi­ called millennials are slowly conque­ help chemical suppliers and buyers ness, digital solutions need to be im­ ring all company departments, and Independence to grow their business network. The plemented. since they were born into the world and Transparency platform offers the possibility to ap­ of digital devices they are not afraid proach multiple companies faster Alexander Lakemeyer, CEO, to take advantage of these opportu­ Pinpools was founded to take ad­ than ever before: By posting a request Pinpools, Haan, Germany nities. Especially these people with vantage of chemical digitalization for quotation a buyer can be contac­ a digitalized mindset are more wil­ by creating a B2B online platform ted by suppliers and then choose the ling to try out new practices, which for selling and buying chemicals. one who offers the best price. is going to be a changing factor for Within just a few years, the company chem­ical business. The millenials has grown rapidly and is currently have developed an expectation with the only independent B2B platform Data Security regard to their way of working that in Europe, i. e. it is not owned by they have immediate access to every any other bigger chemical company. Cloud services, which have become human being at all times. By ha­ Transparency of the website secu­ common in the past years, enable a [email protected] ving this mindset when doing busi­ res trust among the companies do­ faster data transfer. Data security is a www.pinpools.com

CHEManager | Fine & Specialty Chemicals 23 T e c h n o lo g y & I n n o vat i o n

Analyzing Pores Deep-Down Quality Control of Porous or Granular Substances with Modern Image Processing

Autonomous vehicles, self-learning machines, interconnected sys- Combining AI and image processing tems of production and storage units or self-stocking warehouses: in the context of machine learning enables the advancement of systems The digitalization of society and the industrial revolution are moving that help users to identify the crite­ relentlessly forward and offer technologies and innovations with a ria which are relevant to quality in the first place. A self-learning system bright and promising future that are already reality or just one step can be fed with data relating to pro­ away. And in all industrial sectors the relevance of image proces- duction, surroundings and images to­ Daniel Balser, gether with information about quality Strelen sing is continuously on the rise. parameters, error classes or other assessment values. While running, the system gathers all the data of working of production — and solu­ Image processing includes the cap­ limited indeed. In recent years this the production process and assesses tions based on the analysis of digital turing, modification and analysis of boundary has been steadily ­pushed these autonomously. These assess­ images are subsequently becoming images, for instance in the context outwards and previously unimagin­ ments can subsequently be correc­ more and more popular. The market of production or packaging proces­ able performance has become pos­ ted by the user if needed. Over time for companies offering image proces­ ses. The main objective is to extract sible. For the largest part this is due such a system will increase its pre­ sing solutions is still young but has relevant information from the ima­ to the greatly increased capacity of cision progressively. Parameters that grown rapidly in the last few years ges in order to steer processes, test computer processors and graphic are critical for the quality can thus be — with no end in sight. The chemi­ products, document completeness or chips. Additionally, image proces­ identified among all incoming data as cal sector is especially eager to use so integrity or perform general quality sing is of relevance to the develop­ well as parameters that do not corre­ called “machine vision” systems. One control. ment of artificial neural networks, late with quality at all. example of a practical application is For a long time, the potential to which are relentlessly gaining in im­ The fourth industrial revolution determining the chemical composi­ use image processing to gain infor­ portance since they further the deve­ brings great challenges — as men­ tion of substances with the help of hy­ mation and steer processes was very lopment of artificial intelligence (AI). tioned above, digitalization and net­ perspectral imaging. ©unpict - stock.adobe.com

24 CHEManager | Fine & Specialty Chemicals T e c h n o lo g y & I n n o vat i o n

a) b) c) foamed plastic or construction mate­ rials, packaging, foam material or ba­ kery products — can be analyzed in this manner. It is also possible to de­ tect and analyze foreign particles dif­ fering in color or suspended solids in a carrier medium. This technology is employed in Safe-Ident Cell, which is the new pro­

© Strelen © Strelen © Strelen duct of image processing company a) 8-bit grey-scale image of a porous plastic; b) binary image after application of the threshold filter; c) found pores are Strelen Control Systems. The system marked in purple. offers the solution for offline test sta­ tions which need to quickly and sim­ So-called blob analysis is a further cific aspects which will later be recog­ background. These can be dark areas ply determine the composition of example. It is used in many applica­ nized by an algorithm. It might for in­ on light background or vice versa — a material, the number and size of tions that fulfil requirements of the stance be an advantage to increase e. g. impurities or pollution on a sur­ ­pores or the presence, frequency and chemical industry, such as examining the contrast of the image so that light face. If dark areas need to be detected quality of particles. The software uses porous and granular substances in or­ or dark parts can be separated more in light surroundings, the algorithm data logging to guarantee an over­ der to define relevant quality parame­ easily later on. finds black pixels and compares them view of all collected data and deter­ ters, respectively verify these. Before, The next step is the creation of to their immediate surroundings to mines time trends in production qua­ these kinds of analyses would have the binary image by using a so-called establish connected areas of black pi­ lity. By offering the implementation of required a lot of time and personnel, threshold-filter. It is called this be­ xels which form a so-called blob. In varying cameras and optics this solu­ if they were even possible at all. Blob cause it is based on a threshold to this way each black pixel is as­signed tion can be adjusted to different ob­ analysis is based on digital images ta­ which the brightness value of each to its own specific cluster and can ject sizes, operating distances and ken by industrial cameras. As a rule, pixel is compared. Is the value below thus be sorted, differentiated and sta­ monitoring stations, thus allowing for these are grey-scale images which the threshold, the pixel is assigned tistically analyzed. It is possible, for customized solutions. This kind of so­ means each pixel can be represented the value 0, meaning it is turned example, to only evaluate blobs with a lution is in high demand in the indus­ by a brightness value. If we take an black. All other pixels are assigned certain dimension, a minimum round­ try and it is universally applicable, as 8-bit grey-scale image, each pixel can the value 255 and subsequently turn ness or blobs in defined, distinct areas is shown by the successful implemen­ have 28, or 256, different values of white. After applying the filter, the of the image. All blobs which meet the tations in the cosmetic, chemical and brightness. A value of 0 represents a image finally consists of only black criteria can be assigned specific va­ pharmaceutical sectors, where the black pixel, 255 a white one. In order and white pixels. It is of great impor­ lues such as quantity, area, height, company is currently working on the to gain further information using blob tance for the subsequent quality and width, circumference, roundness and realization of a particle detector. analysis, the grey-scale image needs precision of the blob analysis that the a number of values derived of these. to be transformed into a binary image threshold is set to a suitable value. It is thus for instance possible to cal­ Daniel Balser, project engineer, which only contains the values 0 and The binary image can then be eva­ culate what percentage of the total Strelen, Griesheim, Germany 255. The first step is to use filters on luated using analytic algorithms. Blob area is covered by the blob or the size the original grey-scale image in order analysis helps to find image areas of the blob in relation to position. But [email protected] to eliminate errors or to highlight spe­ where the brightness differs from the not only porous materials — such as www.strelen.de

Afyren and SPI Industrial Projects Fund Create JV BASF Opens Catalysts and Process Research Center

Afyren, a French biochemicals com­ The new plant will be based at the BASF has inaugurated a research BASF, the company is investing a sin­ pany, and Bpifrance, through its SPI Chemesis industrial park in Carling- center for catalyst and process de­ gle-digit million euro sum per year in industrial projects fund, have fina­ St. Avold, France, to benefit from in­ velopment at its Verbund site in Lud­ this project. lized the agreements for the creation dustrial synergies with the platform’s wigshafen, Germany. The new faci­ After completion of the moderni­ of their joint subsidiary Afyren Neoxy. major operators, one of them being lity will be operated by the global zation, which is expected to take se­ This company, backed by a capital of energy and petrochemicals company research unit Process Research & veral years, this building is planned nearly €50 million, will house the first Total. Based on co-products from the Chemical Engineering. The new pi­ to become the central hub for expe­ industrial unit based on the biomole­ sugar industry, this unit will produce lot plant houses highly automated rimental work with automated pilot cule production technology developed a range of seven organic acids with experi­mental facilities for process de­ plants for liquid and gaseous subs­ by Afyren, which successfully com­ an initial capacity of 16,000 t/y. This velopment and testing of new process tances. pleted a final pre-industrial phase in project is expected to contribute to catalysts. According to BASF, the mo­ “With the increasing importance 2018, validating the efficiency of its the region’s reindustrialization and dernized lab features a modular con­ of the BASF segments Chemicals and non-GMO and zero-waste biological the development of green chemicals struction of the testing facilities, the Industrial Solutions, there is a gro­ processes. with the Chemesis platform. Afyren use of digital technologies to better wing need for product research and This agreement follows the Neoxy plans to generate 60 new jobs visualize and manage the pilot plants, especially process research,” said €21 million of funds raised in January by 2021. and a digitalized working environ­ Detlef Kratz, head of the research 2019, and is part of the €60 million Nicolas Sordet, Afyren’s CEO: ment. unit Process Research & Chemical global financing program, with which “Through this joint initiative with To implement this concept, a 60- Engineering. Afyren wants to take its industrial Bpifrance, we will be able to benefit year old building was completely gut­ The concept of the new pilot plant project forward through to its mar­ from the financial resources needed ted and modernized over the past also includes professional data ma­ ket release. The SPI fund will invest to industrialize our technology and 2 years. While research can now be nagement. The seamless integration €23 million for a 49% stake in Afyren the confidence and trust of a major carried out on the ground floor of the of process and analysis data should Neoxy, with Afyren holding the remai­ institution, which will be a key factor building, the renovations will con­ enable automatic data integration ning 51% of its capital. supporting our development. (rk) tinue on the next floor. According to and evaluation of processes. (rk)

CHEManager | Fine & Specialty Chemicals 25 E v e n t s / I n d e x / I m p r i n t

Chemspec Europe ChemOutsourcing Chemspec Europe will take place on June 26–27, 2019, in Basel, Switzerland. A ChemOutsourcing, to take place on Sep. 16–18, 2019, in Long Branch, NJ, USA, key platform for manufacturers, suppliers and distributors of fine and specialty addresses chemists, business development personnel and buyers from the chemicals, the event showcases products and services to a dedicated audience pharmaceutical, biotech, chemical, and chemistry services industries. It focuses of professionals in the industry sector. The product portfolio of this internatio­ on API development spanning early drug discovery through chemical develop­ nal exhibition covers a maximum range of fine and specialty chemicals for vari­ ment and commercial supply. Attendees are executive scientist “buyers” from ous industries. Networking opportunities and conferences presenting the latest pharmaceutical companies responsible for sourcing starting materials, inter­ results of ongoing R&D projects round-off the show. www.chemspeceurope.com mediates, active ingredients, and commercial supply. www.chemoutsourcing.com

Specialty & Agro Chemicals America CPhI Worldwide On Sept. 4–5, 2019, Specialty & Agro Chemicals America, to take place in Charles­ CPhI Worldwide, taking place on Nov. 5–7, 2019, in Frankfurt, Germany, houses ton, SC, USA, focuses on the chemical products and technologies that have spe­ six individual pharma events covering all industry sectors. 2,500+ exhibitors cific applications for the agrochemical and specialty chemical manufacturing from more than 150 countries gather at the event to network and take advan­ markets. The event narrows the focus and renews the value for chemical indus­ tage of free industry seminars. Every sector of the pharmaceutical market is try attendees. Participants cover a diverse range of chemical end-uses including represented under one roof. In 2019, two new podiums will be introduced: Na­ adhesives & sealants, agriculture & crop protection, coatings & paints, cosmetics tural Extracts, based in the Natural Extracts zone, with content that covers this & personal care, flavors & fragrances, oilfield & lubricants, pharmaceuticals, segment of the industry; and World of Pharma, which will look mainly at regio­ plastics & composites, and water treatment. www.chemicalsamerica.com nal trends and updates. www.cphi.com

Index Imprint

Abbvie 17 Innovation Institute (ISI) 18 Publisher Team Assistants ACG Pharma Outside Back Cover Insight Health 16 Wiley-VCH Verlag GmbH & Co. KGaA Bettina Wagenhals Tel.: +49 6201 606 764 Afyren 25 International Council of A Company of John Wiley & Sons, Inc Boschstr. 12, 69469 Weinheim, [email protected] AkzoNobel 6, 8 Chemical Associations (ICCA) 9 Germany Lisa Rausch Alantra 4 Lonza 16 Tel.: +49 6201 606 0 Tel.: +49 6201 606 316 Alcami 16 Mack Brooks Exhibitions Inside Back Cover [email protected]

Amgen 16 Mergermarket 4 General Managers Beate Zimmermann BASF 4, 20, 25 Microinnova Engineering 20 Sabine Steinbach Tel.: +49 6201 606 316

Bernstein 16 Mylan 16 Dr Guido F. Herrmann [email protected]

Biesterfeld Spezialchemie 15 Nouryon 8 Publishing Director Wiley Reader Service Biogen 16 Nova Institut Inside Front Cover Dr. Heiko Baumgartner 65341 Eltville Blacktrace Holdings 19 Oxford Economics 9 Tel.: +49 6123 9238 246 Product Management Bpifrance 25 Patheon 16, 20 Fax: +49 6123 9238 244 + Managing Editor E-Mail: [email protected] British Biosimilars Association 16 Photanol 8 Dr. Michael Reubold Catalent 16 Pinpools 23 Tel.: +49 6201 606 745 [email protected] Original Articles: C-Bridge Capital 16 Port of Amsterdam 8 Specially identified contributions are the CESIO 10 Pro Biosimilars 16 ­responsibility of the author. Manuscripts Editor in Chief should be addressed to the editorial office. Charles Barker Corp. 4 Roland Berger 23 Dr. Ralf Kempf Instructions for au­thors may be requested Tel.: +49 6201 606 755 from the publishing­ company. We assume­ no ChemSec 6 Samsung Bioepsis 16 [email protected] liability for unsolicited, submitted ma­ Clariant 20 Sandoz Biotech 16 nuscripts. Reproduction, including excerpts, is permitted only with the permission of the Commonwealth Scientific and Sanofi-Aventis 20 Freelancer editorial office and with citation of the source. The pub­lishing company is granted the ex­ Industrial Research Organisation (CSIRO) 19 Siegfried 13 Volker Oestreich Thorsten Schüller clusive, space and content restricted right to Ehrfeld Mikrotechnik 18, 20 Sinochem 4 arbitrarily use the unmodified work/editorial contribution for all purposes for itself and for Elix Polymers 4 Strelen Control Systems 24 Media Consultants businesses that have an interest in the publi­

Enerkem 8 Syngenta 4 Thorsten Kritzer shing company as defined by company law Tel.: +49 6201 606 730 as well as to transfer the right of use to third European Union 16 Syrris 20 parties. This right of use applies to both print [email protected] and electronic media including the internet Formycon 16 Tata Steel 8 and data banks/data media of all types. Frost & Sullivan 14 Thyssenkrupp 8 Jan Käppler Tel.: +49 6201 606 522 All names, designation, or ­signs in this issue, Google 23 Umicore 11 [email protected] whether ­referred to and/or shown, could be trade names of the respective owner. Häffner 7 Universita di Perugia 20

Holiferm 8 University of Graz 18 Production Managers Printed by: DSW GmbH, Jörg Stenger Ludwigshafen, Printed in Germany Hovione 4 Valsynthese 5 Melanie Horn (Advertising) Imax 4 Wanhua Chemical 4 Oliver Haja (Layout)

InnoSyn 20 Yantai Wanhua 4 Elke Palzer (Litho)

26 CHEManager | Fine & Specialty Chemicals FOCUUS: Bio-basede Fine ChC emiccala s + Bio-based BuB illddiing Blockcks & PPolymers + Biodeegradaable Solutions + Innon vation Award

HIGHLIGHTS OF THE VOTE FOR WORLDWIDE BIOECONOMY the Innovation Award • Vision & Policcy • NEW BBio-o bbased FiFinen “Bio-based Material Chemmiccala s (Food Inngrrede ieentntss, of the Year 2019”! • BBio-o baaseed Buuilldingng Blocks Flavours, Bodyy Care,e • Bio-based PoPolyymeers Cosmmeticcs, Phharmaceuutit ccals) • Biiodegradable Sooluutions • Innoovatiioonn Award „B„ io-bassede Material Dominik Vogt • Industtriala Bioi techhnology of the Year 220199“ Conferencec Mannaga ere • Biorefineriess ++49 (0)22232 3 488141 -49 Contact dod minik.vogt@@nova-institut.dde WORKSHOPS Assessing Bio-based Product Value Chains – How Better Regulation and Standardisation Can Promote a Level Playing Field Organiser Innovation Award Sponsor Biotechnological Solutions from China In-depth B2C Market Research and GreenPremium Feasibility of a European Lignocellulosic Biorefinery The Difficulties of Building a Biorefinery and bio-based- How to Avoid Them conference.com www.nova-institute.eu www.infraserv-knapsack.de

Pictures: J.Rettenmaier & Söhne, BASF, nova-Institute

More information at: bio-based-conference.com