Global Contract Manufacturing Brochure 2010 by Nycomed Austria GmbH

Nycomed Global Contract Manufacturing Nycomed Global Contract Manufacturing Brochure 2010

Our Global Contract Manufacturing Team As one of the world’s leading pharmaceutical companies, Nycomed not only discovers, develops, manufactures and markets its own products; it also provides contract manufacturing services to third parties throughout the world. In this new brochure for 2010, we provide an overview of the company and explain our understanding of partnership. We also introduce our 8 state-of-the-art plants worldwide offering contract manufacturing and present our wide range of technologies and services.

Nycomed’s policy has always been to provide patients with the very best in terms of quality, reliability and responsiveness. With its contract manufacturing services, Nycomed also shares this approach with its customers - who expect a strong and economically sound partnership with us. We offer the highest level of customer focus in terms of reliable communication; this is why our clients are directly linked to the operational managers at the various manufacturing sites.

Austria/Linz

Belgium/Brussels

Brazil/Jaguariuna

Denmark/Roskilde

Germany/Oranienburg

Germany/Singen

Mexico/Mexico City

Norway/Elverum

Poland/ Łyskowice

Contents

About Nycomed

Nycomed at a glance Manufacturing Contract manufacturing

Global Presence

Global presence in manufacturing Nycomed plants providing contract manufacturing services

Technologies

Overview of pharmaceutical technologies Solids Semi-solids Non-sterile liquids Sterile / special preparations

Services

Packaging Development Overview of quality standards

Contact

Contacts for building up partnerships

Nycomed Global Contract Manufacturing Brochure 2010

An innovative pharmaceutical company with a solid product portfolio, promising pipeline and global reach, particularly in emerging markets.

About Nycomed

Nycomed - a global market-driven growth company

Nycomed at a glance Nycomed is a privately-owned global pharmaceutical company with a differentiated portfolio focused on branded medicines in the areas of gastroenterology, respiratory and inflammatory diseases, pain, osteoporosis and tissue management. An extensive range of OTC products completes the portfolio. Research and development is conducted at three sites in Europe and one in India. New products are sourced from our own internal discovery organisation and in-licensed from external companies such as small biotech organisations. Establishing long-term partnerships is a cornerstone of Nycomed´s growth strategy. Nycomed has 16 manufacturing sites: 5 centres of competence in Europe for global products and 11 production sites for regional products in fast-growing markets such as Brazil and Mexico. A major investment is currently being made in a new pharmaceutical plant in Russia, at present Nycomed’s biggest single market.

2009. Nycomed ranks 28th among global pharmaceutical companies and is the 16th largest provider of OTC medicines. For more information visit www.nycomed.com

Our mission Our mission is to bring medicines that matter to patients and healthcare providers. Our vision Our vision is to become the preferred pharmaceutical company by being responsive, reliable and focusing on results. Company values Nycomed people are encouraged to think for themselves along with the company. Our inherent values “Empathy, Courage, Trust and Motivation” help us create an environment, where highly motivated and committed employees deliver results.

Nycomed employs 12,000 people worldwide and has affiliates in more than 50 countries. It has a strong presence in Europe and in the emerging markets in Russia/Commonwealth of Independent States, Asia and Latin America. Headquartered in Zurich, Switzerland, the company generated total sales of € 3.2 billion and an adjusted EBITDA of € 1.1 billion in Nycomed Global Contract Manufacturing Brochure 2010

Competence is more than the sum of individual skills.

Nycomed Global Contract Manufacturing Brochure 2010

About Nycomed

Manufacturing “Operational excellence in mastering the supply chain” Our manufacturing operations provide a competitive advantage for the whole company through an innovative, global supply chain network. This network is constantly reviewed and optimised in the interests of increasing the utilisation of its capacity, enhancing supply chain performance, maintaining a high level of customer service and decreasing the cost of goods sold (COGS). Thus, it delivers Nycomed’s products and services to its customers with the right balance of quality, reliability, responsiveness and costs. Ensuring the availability of Nycomed products and services for customers in the most efficient manner possible requires an integratedapproach. Nycomed’s operational activities are part of the company's value stream. A significant volume of contract manufacturing further optimises the utilisation of the manufacturing network. Currently, we operate 16 manufacturing facilities in 12 countries. These meet the highest international quality standards. Our combination of central and regional manufacturing ensures rapid response when opening up new and expanding existing markets. Partnership plays a vital role in all of our operational activities. Close cross-functional collaboration and seamless processing between internal teams and external partners help us to respond quickly and accurately to market demand.

Competence centres As a part of the continuous optimisation programme for our production network, we have established competence centres for certain technologies and/or pharmaceutical business areas. This helps us to increase capability in our core competence areas. CENTRES OF COMPETENCE FOR GLOBAL PRODUCTS Asker, Norway: solid forms of calcium Linz, Austria: sterile ampoules, biologicals and packaging Lyszkowice, Poland: OTC products in solid and non-sterile liquid forms Oranienburg, Germany: development, production and packaging of solid dosage formulations; and niche technologies, such as pellets and stick packs Singen, Germany: liquids (including sterile liquids in ampoules, vials and syringes), semi-liquids, stick packs and ointments “Partnerships are the key to our success“ Partnerships play an essential role at Nycomed. Wherever we operate, we offer our research, development, regulatory, manufacturing, marketing and sales expertise to our partners. And, where we are not present, we are willing and ready to cooperate. Around the world, we are currently working with up to a hundred partners; this allows us to adapt our capabilities to meet market needs. Identifying good partners and managing long-term relationships is part of our company philosophy.

Nycomed Global Contract Manufacturing Brochure 2010

About Nycomed

Contract manufacturing “Part of Nycomed's Operations Strategy.“

Subsequent to initiating the concept of production network optimisation in 2007, Nycomed established a global organisation for contract manufacturing based on a broad range of technologies, services and incorporating the competence of a successful mid-sized pharmaceutical company. Local responsibility With the know-how and the capacity of our plants throughout the world, we at Nycomed are close to our customers in all important markets. Being near to our clients is part of our understanding of providing full service. As every client and every task has quite specific requirements, Nycomed has to approach each situation as if it were unique. We thus tailor our services towards specific customers and tasks. In this way, we can provide the service that is needed. Certificated by the most stringent and demanding authorities, Nycomed delivers its services worldwide. It also provides its expertise not only in scientific matters but also by supplementing our clients' understanding of their target markets for the supply and distribution of products. Operational Excellence (OpEx) Nycomed has placed high priority on continuous improvement throughout the whole organisation by focusing on the needs of their customers, empowering its employees and

Nycomed Global Contract Manufacturing Brochure 2010

optimizing existing production processes. Our production site in Elverum, Norway is a good example. In 2009, the site received a company award for optimising the production of a fluoride dental rinse. In a separate initiative, a nasal spray production line was reengineered based on direct input from employees and the help of our ‘green belts’ – with a resulting 50% improvement in two key process steps. Furthermore, this site has also received several awards for supplier excellence from a well-known pharmaceutical company. Global presence As a global company, Nycomed can provide a supply chain anywhere in the world, making sure that your products will be available when and where they are needed. Customers from all parts of the world, from small, emerging and large pharmaceutical companies already use these services. We are confident that you will benefit from our services too.

Global CM organisation dedicated to the management of external partners.

Trust, versatility, competence, reliability at your service throughout the world.

Global Presence

Global presence in manufacturing. under construction

Europe

Argentinia

Austria

Belgium

Brazil

Denmark

Estonia

Germany

India

Mexico

Norway

Poland

USA

Russia - Plant under Construction

Nycomed Global Contract Manufacturing Brochure 2010

Global Presence

Nycomed plants providing contract manufacturing services

- An international team of more than 550 - Located in Linz, upper Austria - Production area of 7,543 m2 - Approved by EMA, ANVISA and local authorities - Accredited by the Japanese authorities

AUSTRIA/LINZ Competence centre for sterile ampoules and biological products with vast expertise in the processing of biologics (animal or human origin) and authorised to handle narcotic drugs and drug substances.

BELGIUM/BRUSSELS Manufacturing site for solid dosage forms and liquids focusing on the supply of medium-sized batches and with the flexibility to operate in highly competitive markets.

- -

A highly motivated team of 90 Located in Brussels, in the heart of Belgium and Europe Production area of 8,100 m2 Approved by EMA

Nycomed Global Contract Manufacturing Brochure 2010

Global Presence

Brazil/JaguariĂşna Manufacturing site for solid, liquid and semi-solid forms. One of the largest and most modern plants in Latin America complying with global standards.

- An international team of 400 - Located 130 km south west of Sao Paulo - 3 state-of-the-art production facilities with a production area of 14,050 m2 - Approved by FDA, EMA and local authorities

Germany/Oranienburg Competence centre for the development, production and packaging of solid dosage forms. Supplies the pharmaceutical markets in more than 100 countries, from Europe to the US and Japan. Large-scale production focusing on high throughput.

- An international team of 430 - Located in the heart of Europe, 30 km northwest of Berlin, Germany - Two state-of-the-art production plants covering 12,900 m2 - Approved by FDA, EMA

Nycomed Global Contract Manufacturing Brochure 2010

Global Presence

- -

An international team of 750 Located in Singen, Germany (close to the Lake of Constance) State-of-the-art plant with a production area of 30,000 m2 Approved by FDA, EMA, ANVISA and local authorities

- An international team of 342 - Located in the suburb of Naucalpan, in the western part of the Greater Mexico City Metropolitan Area - Two state-of-the-art facilities with a production area of 4,019 m2 - Approved by local authorities (SSA Mexico & INVIMA Colombia)

Germany/Singen Competence centre for sterile dosage forms processed aseptically or terminally sterilised and including freeze-dried vials. As one of Nycomed's largest production plants, Singen manufactures non-sterile liquids, semi-solids and special preparations such as nasal sprays.

Mexico/Naucalpan Manufacturing site for solid dosage forms of OTC and RX products. Supply of the local market as well as Central America, the Caribbean, Venezuela, Peru, Colombia, Ecuador and Chile.

Nycomed Global Contract Manufacturing Brochure 2010

Global Presence

Norway/Elverum Manufacturing site specialised in the production of liquids, mainly sterile liquids, filled in plastic ampoules (BFS) as well as non-sterile liquids filled in plastic ampoules, spray pump vials and bottles.

- An experienced team of 170 - Located 100 km north of Oslo Airport Gardermoen - Compact manufacturing unit covering a production area of 3,400 m2 - Approved by EMA

Poland/Ĺ yskowice Competence centre for our solid and non-sterile liquid OTC products. Produces a wide variety of pharmaceutical, dietary, nutritional and cosmetic products with a focus on quality and efficiency. Special expertise in the processing of vitamins.

- A dedicated international expert team of 280 - Located in the heart of Poland - State-of-the-art plant with a production area of 2,918 m2 - Approved by EMA and local authorities

Nycomed Global Contract Manufacturing Brochure 2010

Achieving the highest possible quality is a matter of course - our maxim is safety and convenience.

Pharmaceutical Technologies

Overview of pharmaceutical technologies By using our contract manufacturing services you can access Nycomed's comprehensive technology portfolio for pharmaceuticals and the competence we have built up over decades. Knowledge, modern technology and creativity

combined with clear and well-defined communication procedures between our teams of experts and customers are the key factors for achieving optimum solutions that will surely exceed your expectations.

Solids

Semi-solids

Non-sterile liquids

Steriles ▪

Austria / Linz Belgium / Brussels

▪

Germany / Oranienburg

▪ ▪

Germany / Singen Norway / Elverum

▪

Poland / Łyskowice

▪

Brazil / Jagúariuna

▪

Mexico / Mexico City

▪

HIGHLIGHTS Austria / Linz: Expertise in processing biologics (human or animal origin) Belgium / Brussels: Small-/ mid-sized products, organic coating Germany / Oranienburg: Pellet/ granule technology (minimum filling weight of 100 mg), organic solvents in granulation, coating, wallet packaging Norway / Elverum: Blow-Fill-Seal technology (BFS) Poland / Łyskowice: OTC and food supplements, vitamin products, sachet filling, organic coating

Nycomed Global Contract Manufacturing Brochure 2010

Pharmaceutical Technologies

Solids

Our technology portfolio for the bulk production of solids comprises: - - - -

Granulation (wet, fluid bed with aqueous and organic solvents) Roller compaction Pellet production (non-pairelles, extrusion, Wurster coating) Tableting (cores for various tablet types, e.g. bi-layer, micro- or controlled-release tablets) - Encapsulation (hard shell) - Coating (aqueous, organic, sugar or double-layer coating) - Imprinting

Whatever you need in the way of solid dosage forms - tablets, coated tablets, pellets or capsules - you can trust Nycomed with your projects and products. Nycomed provides both basic and specialised technologies for bulk clinical supplies, bulk production and packaging.

Pellets/granules

Film-coated Tablets

Belgium / Brussels

▪

Germany / Oranienburg

▪

Poland / Łyskowice

▪

Brazil / Jagúariuna

▪

Mexico / Mexico City

▪

Solids are the dominant dosage forms and are subject to constantly changing requirements. Nycomed has invested in the most advanced technologies available.

Nycomed Global Contract Manufacturing Brochure 2010

Sugar-coated Tablets

Capsules

Pharmaceutical Technologies

Semi-solids Elverum has a key competence in BFS technology, in this case for the filling of gels. Filling capacities for local markets are also available in the plants in Brazil and Mexico.

Several Nycomed sites are capable of manufacturing semi-solids: Singen, one of the major sites, covers the whole portfolio from gels to suppositories. Filling into stick packs for gels is unique here within our operations network.

Creams

Ointments

Suppositories

Germany / Singen

▪

Brazil / Jagúariuna

▪

Mexico / Mexico City

▪

Nycomed has proven technologies and expertise in the manufacture of a number of semi-solid products.

Nycomed Global Contract Manufacturing Brochure 2010

Pharmaceutical Technologies

Non-sterile liquids Nycomed has substantial product expertise in the production of both sterile and non-sterile liquids. With our comprehensive general and niche technologies, our production capabilities for non-sterile liquids range from nutritinal and

vitamin products to state-of-the-art prescription drugs. The majority of the vitamin products and nutritionals provided to our clients are manufactured at Lyszkowice in Poland.

Solutions

Suspensions

Austria / Linz

▪

Germany / Singen

▪

Norway / Elverum

▪

Poland / Łyskowice

▪

Brazil / Jagúariuna

▪

Mexico / Mexico City

▪

Applications for non-sterile liquids: - Nasal applications (drops, sprays, rinsing fluids) - Eye drops - Oral drops - Vitamin syrups - Ethanolic solutions

Nycomed Global Contract Manufacturing Brochure 2010

Gels

Syrups

Ethanolic liquids ▪

Pharmaceutical Technologies

Steriles handle hazardous goods such as psychotropic substances. We supply liquid sterile products aseptically filled as well as terminally sterilized. Elverum applies its Blow-Fill-Seal technology for filling sterile products.

Whether semi-solids or liquids, Nycomed offers a broad range of sterile products in any required form based on a variety of ingredients, including biologics. Among our European sites, Singen and Linz are competence centres for sterile dosage forms and are authorised to

Injectables Austria / Linz

▪

Germany / Singen

▪

Norway / Elverum

▪

Infusion solutions

Gels

▪ ▪

Special Preparations Complementary to our portfolio of sterile products, Nycomed has special expertise in the niche technologies of preparation of sterile powders and sterile suspensions. - Aseptic spray-drying of sterile powders and aseptic filling into bottles - Preparation of sterile suspensions by multi-step dissolution of single compounds, sterile filtration and precipitation under aseptic conditions in a final step.

Nycomed Global Contract Manufacturing Brochure 2010

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Our primary goal is to contribute to the success of our customers; we thus stay close to them from development to delivery.

Services

Packaging Nycomed provides the entire range of packaging technologies for solids, semi-solids and liquids and for sterile and non-sterile products. We also assist our clients in designing the right package to enhance users' understanding of the product and hence also improve compliance.

Our innovative packaging designs have won several design awards. In 2006, Nycomed introduced wallet packaging at our plant in Oranienburg. At Nycomed we constantly continue to strengthen our ability to support our customers with innovative packaging concepts.

Our technology portfolio for packaging of: Solids - Blisters in various formats (PVC, PVC/PVDC, PVC/Alu, Alu/Alu, Aclar, Triplex, COC) - Bottles (glass, PE) - Sachets (Alu/Alu) - Stick packs - Wallet packaging

Liquids - Ampoules (glass, plastic) - Bottles (glass, plastic) - Flaconettes (glass, plastic) - Pre-filled Syringes (glass, plastic) - Sachets - Thermo-shaped units - Vials (glass, plastic)

Packaging development: - Design of packaging format - Development - Material research Semi-solids - Sachets (Alu/Alu) - Stick packs - Thermo-shaped units - Tubes (Alu)

For primary packaging in plastics we apply "BlowFill-Seal" technology using a plastic granulate as well as so-called "ThermoShaped-Units", shaped from two plastic foils and fused together. For all kinds of primary packaging we supply secondary packaging including leaflets and bundling, if applicable. Our glass ampoules are packaged in plastic trays formed by a deep-drawing process.

Liquid preparations in - Blow-Fill-Seal (gels, liquids) - Pump sprays

Nycomed Global Contract Manufacturing Brochure 2010

Services

Development

A team of selected experts provides development services to foster product transfer to the Nycomed operations network. Whether you need assistance in process optimisation, scale-up, optimisation of analytics or CMC-documentation, Nycomed can be of help. With our qualified and dedicated professional staff and excellent laboratory facilities, you can trust us with your development projects, starting with effective product transfer management.

Nycomed Global Contract Manufacturing Brochure 2010

Product development services - Effective transfer management - Optimisation of formulations - Scale-up and optimization of production processes - Optimization of analytical methods - Bulk clinical supplies - Stability testing - Regulatory support (CMC dossier) - Market form design (bulk & packaging)

Services

Overview of quality standards We fulfil the highest of international quality standards. All our manufacturing sites in Europe are regularly inspected by EMA and local health authorities. Our competence centres in Germany have been approved for supply to the USA. Austria will be inspected by the FDA in

Solids

the near future. We are an approved supplier for liquids and semi-solids to Japan. In Latin- and South America, we not only adhere to the strictest local quality standards (ANVISA, INVIMA, etc.) but also to global standards (FDA, EMA).

Semisolids

Liquids

Steriles EMA JAPAN ANVISA FDA approval ongoing

Austria / Linz

Belgium / Brussels

EMA

Germany / Oranienburg

EMA ANVISA FDA INVIMA

EMA

EMA FDA ANVISA JAPAN

Germany / Singen

Norway / Elverum

EMA FDA ANVISA JAPAN

EMA

Poland / Ĺ yskowice

EMA INVIMA

Brazil / Jaguariuna

MERCOSUR EMA COLOMBIA LOCAL AUTHORITIES INVIMA

MERCOSUR FDA LOCAL AUTHORITIES

MERCOSUR COLOMBIA LOCAL AUTHORITIES

Mexico / Mexico City

CENTRAL AMERICA LOCAL AUTHORITIES INVIMA

CENTRAL AMERICA LOCAL AUTHORITIES

EMA

CENTRAL AMERICA LOCAL AUTHORITIES

Nycomed Global Contract Manufacturing Brochure 2010

Close collaboration right from the start.

Contact

Contacts for building and furthering partnerships For further information please get in touch with us. GLOBAL CONTRACT MANUFACTURING Nycomed Denmark Langebjerg 01 4000 Roskilde, Denmark Phone: +45 4677 1462 Fax: +45 4675 6640 contract-manufacturing@nycomed.com www.nycomed.com

Coordination office: Nycomed Austria GmbH St. Peter-Straße 25 4020 Linz, Austria Phone: +43 70 6919 46 93 Fax: +43 73 2655 30 9

AUSTRIA Nycomed Austria GmbH St. Peter-Straße 25 4020 Linz, Austria www.nycomed.at

GERMANY Nycomed GmbH Robert-Bosch-Straße 8 78224 Singen, Germany www.nycomed.de

BELGIUM Nycomed Christiaens SCA/CNA Chaussée de Gand, 615 1080 Brussels, Belgium www.nycomed.be

MEXICO Nycomed México S.A. de C.V. Av. I° de Mayo No 130 Col. Industrial Atoto Naucalpan de Juarez,Naucalpan Edo. Mex., Mexico www.nycomed.mx

BRAZIL Nycomed Pharma Ltda. Rodovia SP 340 Km 133,5 13 800 000 Jaguariuna, Brazil www.nycomed.com.br

NORWAY Nycomed Pharma AS Solbrvegen 5 2418 Elverum, Norway www.nycomed.no

GERMANY Nycomed GmbH, Plant Oranienburg Lehnitzstraße 70-98 16515 Oranienburg, Germany www.nycomed.de

POLAND Nycomed Pharma Sp. z.o.o. Ul. Ksiestwa Lowickiego 12 99-420 Lyszkowice, Poland www.nycomed.pl

Nycomed Denmark Langebjerg 01 4000 Roskilde Denmark

www.nycomed.com

Nycomed Global Contract Manufacturing Brochure 2010

Nycomed Denmark Langebjerg 01 4000 Roskilde Denmark www.nycomed.com