Bringing innovation to global health. Crucell 2010

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1 Bringing innovation to global health Crucell

2 Contents Our mission Crucell s mission is to protect human lives from infectious diseases by bringing meaningful innovation to global health. Research and development see page 12 Crucell is a global biopharmaceutical company focusing on the research and development, production and marketing of vaccines and antibodies against infectious disease worldwide. Currently we are combating twelve major infectious diseases with our range of marketed vaccines in the paediatric, travel and endemic, and respiratory fields. In this report you can read all about our mission, vision, strategic pillars and our commitment to the principles of Corporate Social Responsibility. For inquiries, please contact Corporate Communications. [email protected]. Technologies see page 20 Overview Crucell at a glance 02 Crucell: A global perspective 06 Message from our CEO 08 Our business Research and development, technologies and products 10 Research and development 12 Technologies 20 Products 26 Products see page 26 Crucell s commitment to the world Taking responsibility 32 CSR highlights in Our CSR policy 36 Our CSR achievements, ambitions and targets 40

3 2010 key highlights 01 Revenues and other operating income 2010 Revenues and other operating income ( million) 105+ mln Product sales License revenues 32.7 Service fees 6.5 Other operating income, e.g. grants 35.6 Total Vaccine doses distributed in 2010 In more than 100 countries around the world mln Research and development investment in 2010 Compared to 70.2 mln in Product sales ( million) mln 25% Product sales in % 7% 7% Paediatric Travel and endemic Respiratory Other mln Total revenues and other operating income in 2010 Compared to mln in 2009.

4 02 Overview Crucell at a glance

5 Overview Crucell at a glance 03 Crucell is a global biopharmaceutical company dedicated to bringing meaningful innovation to global health. We do this by discovering, developing, manufacturing and marketing products that combat major threats to the health of people worldwide. Our specialty is fighting infectious diseases a growing healthcare challenge.

6 04 Overview Crucell at a glance Our Company Innovation is the driving force behind our strong research and development (R&D) pipeline, with promising products in pre-clinical and clinical development. In 2010 alone, Crucell distributed more than 105 million 1 vaccine doses in more than 100 countries around the world, and invested million in R&D. Crucell is deeply committed to being a good corporate citizen: a company that creates significant value for society. Our mission is to make a truly meaningful contribution to global health by directing our proven talent for innovation towards the fight against infectious diseases. An entrepreneurial mind-set and social responsibility go hand-in-hand at Crucell. In 2010, 1,400 dedicated and skilled Crucell employees worldwide worked to bring significant benefit to the lives of people worldwide. We are fully committed to the principles of corporate social responsibility (CSR) and place great value on doing more to benefit society than we strictly must do. Our mission underlies everything we do, from our core business activities to the sharing of scientific knowledge and community outreach programs in countries where help is needed the most. The combination of our innovative technologies, our core values and creative minds drives Crucell s success, which we measure in human and business terms. Crucell is headquartered in Leiden, the Netherlands, with offices in China, Indonesia, Italy, Korea, Malaysia, Spain, Sweden, Switzerland, UK, the USA and Vietnam. Our strategy Infectious diseases are a major cause of illness and death throughout the world. The number of infectious outbreaks is increasing for many reasons: higher population density raises exposure to infectious agents, an aging population is more susceptible to infection, and a rise in global travel boosts the potential for spreading diseases across borders. In addition, natural disasters can have a devastating impact on sanitation, hygiene, infrastructure and healthcare facilities. At Crucell, we are dedicated to saving lives and preventing illness around the world. We focus strongly on unmet medical needs in developing countries, where infectious diseases exert their greatest toll. At the same time, we work to protect travelers and vulnerable groups living in industrialized countries. We target major health threats that demand innovative solutions, striving to lead rather than follow. We focus on infectious diseases because these pose an increasingly serious threat to the health of people worldwide and we have the expertise to make a real difference in this disease area. The combination of our scientific know-how, innovative technologies and quality products positions Crucell to become a major player in the biopharmaceutical arena. Our strategy is based on three business drivers: 1. A strong R&D pipeline with promising products in a range of major disease areas. 2. Cutting-edge technologies that enable the discovery, development and production of biopharmaceutical products. These proprietary technologies drive in-house innovation and generate licensing revenue. 3. A broad range of marketed vaccine products that together combat 12 major infectious diseases. 1. Our strong research and development pipeline Innovation is the driving force behind our strong and broad R&D pipeline, with promising products in pre-clinical and clinical development. Product candidates include flu-mab, an antibody effective against a 1 Figure based on Crucell s top five vaccines in terms of sales volumes: Quinvaxem, Hepavax-Gene, Epaxal, Vivotif and Inflexal V.

7 Overview Crucell at a glance 05 broad range of influenza virus strains, tuberculosis and malaria vaccines, and a rabies monoclonal antibody combination all produced on our unique PER.C6 human cell-line technology. Read more on page Our cutting-edge technologies Crucell s proprietary technologies offer unique advantages for biopharmaceutical innovation. This competitive edge is exemplified by our PER.C6 technology, which is ideally suited to the manufacture of vaccines and therapeutic proteins, such as antibodies. Compared to traditional production platforms, PER.C6 human cell-line technology provides higher yields at lower cost, as well as safety advantages. Crucell licenses its PER.C6 technology and other technologies to the biopharmaceutical industry. Important partners and licensees include, among others, Johnson & Johnson, DSM Biologics, Merck & Co., Novartis, sanofi pasteur and Pfizer/Wyeth. Read more on page Our broad range of innovative products Vaccines play a vital role in protecting against diseases and have contributed significantly to the improvement of global health. Currently we are combating twelve major infectious diseases with our range of marketed vaccines in the paediatric, travel and endemic, and respiratory fields. We are one of the major suppliers of vaccines to supranational organizations in the developing world, and the first manufacturer to launch a fully liquid pentavalent vaccine, called Quinvaxem. This innovative combination vaccine protects against five important childhood diseases. Over 200 million doses have been sold since its launch in 2006 in more than 50 GAVI (the Global Alliance for Vaccines and Immunisation) countries. With this innovation, Crucell has become a major partner in protecting children in developing countries. Other products in Crucell s core portfolio include Hepavax-Gene, a vaccine against hepatitis B; Epaxal, the only aluminum-free hepatitis A vaccine on the market; Vivotif and Dukoral, oral vaccines against typhoid and cholera, respectively; and Inflexal V, a virosomal adjuvanted vaccine against influenza. Read more on page 26. Partners and licensees In addition to our own R&D activities, we have strategic partnerships with several leading healthcare companies, such as Johnson & Johnson, DSM Biologics, Merck, Novartis and sanofi pasteur. Through these agreements, our technologies play a vital role in the development of a vast number of vaccines and antibody products.

8 06 Overview Crucell: A global perspective China Marketing and sales. 2. Italy Marketing and sales. 3. Korea Marketing and sales + Manufacturing. 4. Netherlands (Headquarters) Marketing and sales. 5. Spain Marketing and sales + Manufacturing. 6. Sweden Marketing and sales + Manufacturing. 7. Switzerland Marketing and sales + Manufacturing. 8. UK Marketing and sales. 9. USA Marketing and sales.

9 Overview Crucell: A global perspective 07 Research and development Vaccines in development: Flavimun yellow fever vaccine. Influenza Seasonal cell-based seasonal vaccine. Universal Influenza cell-based universal vaccine. Tuberculosis recombinant AdVac based vaccine. Malaria recombinant AdVac based vaccine. Ebola and Marburg recombinant AdVac based vaccine. Technologies PER.C6 human cell line for development and manufacturing. AdVac used with PER.C6 to develop recombinant vaccines. MAbstract to discover novel drug targets and identify human monoclonal antibodies. HIV recombinant AdVac -based vaccine. HPV recombinant AdVac -based vaccine. RSV recombinant AdVac -based vaccine. Human monoclonal antibodies in development: Rabies antibody combination. Influenza antibodies. Hepatitis C antibody combination. Details on page 12 STAR to enhance yields of recombinant human antibodies and proteins. Virosome a vehicle enabling the use of virus antigens in the making of vaccines. Details on page 20 Products Paediatric: Quinvaxem fully liquid vaccine to protect against five important childhood diseases. Hepavax-Gene recombinant hepatitis B vaccine. Epaxal Junior low dosage, aluminum-free hepatitis A vaccine. MoRu-Viraten vaccine for protection against measles and rubella. Travel and endemic: Epaxal aluminum-free hepatitis A vaccine. Vivotif oral typhoid vaccine. Dukoral only internationally licensed oral vaccine against cholera (and ETEC). Respiratory: Inflexal V virosomal adjuvanted influenza vaccine. Details on page 26

10 08 Overview Message from our CEO I am therefore delighted that talks held with Johnson & Johnson during 2010 have resulted in Crucell becoming the center of excellence for vaccines within the world s largest and possibly most respected healthcare company. As a member of the Johnson & Johnson Family of Companies, we can do so much more to make the world we live in a healthier place. The combination of our two companies will enable Crucell to further accelerate growth, and our shared expertise and talent will help to make an even bigger difference in the lives of people worldwide. We are delighted by the prospect of pursuing our mission with the support of Johnson & Johnson that shares our passion for healthcare innovation, our values and our commitment to care for people. Crucell s mission to bring meaningful innovation to global health reflects a deep commitment to improving the lives of people worldwide. This underpins everything we do as a global organization and as individuals united by a common purpose. Protecting and contributing to society in the fullest possible sense and to the best of our ability is our core business, our passion and the essence of our company. Our commitment to the principles of corporate social responsibility is a logical extension of our mission to bring innovation to global health, focusing especially on the prevention of infectious diseases. During 2010, we distributed over 105 million 1 doses of vaccines to people around the world, with the majority going to infants in developing countries. The range of vaccines we have on the market prevents twelve major infectious diseases: childhood infections, travel and endemic illnesses, and respiratory disease. We estimate that a Crucell vaccine was given to 190 individuals 2 every minute during 2010, a thought that makes us very proud. However, I believe that the best measure of our impact on global health is not the number of doses we supply, but the number of deaths and cases of disease we prevent each year. In 2010, Crucell s top-five vaccines prevented more than 3.6 million cases of infectious disease and 809,823 deaths. 1 Crucell s core business is the discovery, development and delivery of innovative solutions for major health threats. Our specialty is the creation of much-needed immunization products: vaccines that safely 1 Figure based on Crucell s top five vaccines in terms of sales volumes: Quinvaxem, Hepavax-Gene, Epaxal, Vivotif and Inflexal V. 2 Figures based on Crucell s top 5 vaccines Quinvaxem, Hepavax-Gene, Epaxal, Vivotif and Inflexal V. Total 101,666,000 doses minus 2% waste (2,033,320 doses) = 99,632,680 doses sold in 2010 / minutes in 2010 = doses administered per minute.

11 Overview Message from our CEO 09 and effectively mobilize the body s own immune defenses against infections, and antibodies that provide ready-made immune protection against invading microbes. After clean water, immunization is believed to be the most cost-effective health intervention and its key role in promoting the socioeconomic development of countries is becoming increasingly clear. The world population is predicted to reach 7 billion in 2011 and protecting these billions of individuals from infectious diseases is more important and challenging than ever. Trends such as climate change, globalization, urbanization, wider travel and population aging are presenting new opportunities for infectious pathogens to thrive and spread. Doing our utmost to tackle this problem is our primary responsibility and our privilege. It lies at the heart of Crucell. More importantly, I see that we are expanding the boundaries of that reality, day by day. Innovation is the foundation on which Crucell was built, and the fuel driving us forward. Crucell s core business is the discovery, development and delivery of innovative solutions for major health threats. Our achievements so far are thanks to the tireless efforts and dedication of our loyal employees, Crucell s most important asset. In 2010 hundreds of talented people were recruited in order to further boost our capacity to bring innovation to global health going forward. Improving healthcare access The cover photograph of this booklet shows an Expanded Program on Immunization (EPI) session set up by the nongovernmental organization Friendship in collaboration with local governmental agents in Bangladesh. The mothers holding young babies are waiting in line for their infants to receive Crucell s Quinvaxem vaccine. With support from Crucell, Friendship has set up the cold chain to enable children in these remote char areas to be immunized. This initiative is one of many described in our corporate social responsibility (CSR) report in this booklet. The EPI was established by the World Health Organization (WHO) in 1974 with the aim of ensuring that all children in all countries benefit from life-saving vaccines. The first diseases targeted by the EPI were diphtheria, pertussis (whooping cough), tetanus, measles, poliomyelitis and tuberculosis. In 1977, the WHO established global policies for immunization and set the goal of universal immunization for all children by 1990, as an essential element of the WHO strategy to achieve health for all. In 2009, an estimated 82% of children globally had received at least three doses of diphtheria tetanus pertussis vaccine (DTP3) by one year of age, which has traditionally been used as an indicator of EPI coverage. Additional vaccines have progressively been added to the original six recommended by the WHO in The EPI remains committed to the goal of universal access to all relevant vaccines for all at risk. Information on the EPI was sourced from the WHO website. Ronald H.P. Brus President and Chief Executive Officer Leiden, the Netherlands, April 18, 2011

12 10 Our business Research and development, technologies and products At Crucell we bring meaningful innovation to global health. We do this by discovering, developing, manufacturing and marketing products that combat major threats to the health of people worldwide. Our specialty is fighting infectious diseases a growing healthcare challenge. In the following pages we highlight Crucell s key innovations in the field of research and development, our cutting-edge technologies and robust product portfolio. Research and development mln Invested in research and development in mln Doses distributed in Technologies 100 countries Crucell vaccines were distributed in more than 100 countries in Products

13 Our business Research and development, technologies and products 11 Development stage Discovery/ Pre-clinical Phase I Phase II Phase III Marketed Description Marketed products: Quinvaxem Fully liquid vaccine for protection against five childhood diseases. Hepavax-Gene Recombinant hepatitis B vaccine. Epaxal Junior Low-dosage, aluminum-free hepatitis A vaccine (0.25ml). MoRu-Viraten Vaccine for protection against measles and rubella. Epaxal Aluminum-free hepatitis A vaccine. Vivotif Oral typhoid vaccine. Dukoral Only internationally licensed oral vaccine against cholera. Inflexal V Virosomal adjuvanted influenza vaccine. Vaccines in development: Flavimun Yellow fever vaccine. Tuberculosis Recombinant AdVac -based tuberculosis vaccine. 1 Malaria Recombinant AdVac -based malaria vaccine. 2 Ebola and Marburg Recombinant AdVac -based Ebola and Marburg vaccine. 2 HIV Recombinant AdVac -based HIV vaccine. 3 Cell-based Influenza Seasonal influenza vaccine produced on PER.C6. Universal influenza Universal influenza vaccine produced on PER.C6. HPV Recombinant AdVac -based HPV vaccine. 4 RSV Recombinant AdVac -based RSV vaccine. 5 Human monoclonal antibodies in development: Rabies antibody combination Mix of two monoclonal antibodies for post-exposure treatment of rabies. 6 Influenza antibodies Hepatitis C antibody combination 1 Partnered with Aeras. 2 Partnered with NIH/NIAID, GSK. 3 Partnered with Harvard. 4 Human papilloma virus (HPV), partnered with Johnson & Johnson. 5 Respiratory syncytial virus (RSV), partnered with Johnson & Johnson. 6 Partnered with sanofi pasteur. Antibodies neutralizing a wide range of influenza subtypes, including H5 and H1. Neutralizing monoclonal antibody combination across all genotypes tested.

14 12 Our business Research and development

15 Our business Research and development 13 Crucell s research efforts focus on developing vaccines and antibodies that address infectious disease and unmet medical needs. In this section you can read more about the discovery and development of next-generation medical products facilitated by our range of innovative technologies.

16 14 Our business Research and development Our strong research and development pipeline Innovation is the driving force behind Crucell s future growth supported by a strong R&D pipeline. Our scientists focus on the discovery and development of much-needed solutions for major threats to human health particularly vaccines and antibodies for the prevention and treatment of infectious diseases. This has resulted in a broad pipeline of investigational products with the potential to revolutionize the fight against diseases such as influenza, rabies, malaria and tuberculosis. Vaccine development: based on AdVac technology AdVac technology involves the use of novel adenoviral vectors, such as Ad35 and Ad26, in vaccines for diseases caused by viruses, bacteria or parasites. These vectors are harmless adenoviruses that have been disabled so that they cannot replicate. A vector functions as an efficient gene taxi, delivering into the human body a fragment of DNA that carries the code for a protein of a specific pathogen. Once inside the body, the vectors express (produce) these proteins and present them to the person s immune system, which mounts its protective response. Using this versatile vaccine vector platform in combination with our PER.C6 manufacturing technology, we are working with our partners to develop vaccines against major threats to human health, including tuberculosis, malaria, Ebola and Marburg, HIV, human papilloma virus (HPV) and respiratory syncytial virus (RSV). See page 17. Tuberculosis (Phase II) Crucell joined forces with the nongovernmental organization (NGO) Aeras Global TB Vaccine Foundation in 2004 to develop a safe, effective and affordable vaccine against tuberculosis (TB). The traditional TB vaccine developed more than 85 years ago, Bacille Calmette Guérin (BCG), does not reliably prevent pulmonary disease the most common form of TB so there is a great need for a better alternative. Together with Aeras, we are developing the novel TB vaccine candidate AERAS-402/Crucell Ad35. The vaccine is based on Crucell s innovative AdVac technology, which uses novel harmless adenoviruses as vaccine vectors (vehicles). We are using the adenovirus 35 (Ad35) vector for this particular vaccine. AERAS-402/Crucell Ad35 is being designed as a booster vaccine that will be given to people who have previously been vaccinated with the traditional TB vaccine or an improved, recombinant version of the BCG vaccine that is being developed by Aeras. The BCG vaccine will prime (prepare) the immune system to fight off TB infection and the AERAS-402/ Crucell Ad35 will be given later to boost this initial immune response. Data from AERAS-402/Crucell Ad35 clinical trials (Phase I and II) support the immunogenicity and acceptable safety profile of the candidate TB vaccine. In 2009, an estimated 1.7 million people died of tuberculosis. Source: WHO, Global TB Control 2010 report. Tuberculosis Estimated new TB cases (all forms) per 100,000 population in >300 No estimate

17 Our business Research and development 15 Malaria Countries or areas at risk of transmission in Transmission occurs Limited risk of transmission No report Source: WHO, World Malaria Report Malaria (Phase I) Malaria is one of the most prevalent infections in tropical and subtropical regions. Children and pregnant women are most severely affected. According to the World Health Organization (WHO), half of the world s population is at risk of malaria, and an estimated 225 million cases led to 781,000 deaths in There is currently no licensed vaccine to protect people against malaria, a disease caused by infection with the Plasmodium parasite and transmitted by mosquitoes. Therapies are available for malaria patients, but the worsening problem of drug resistance in many parts of the world is making adequate treatment and control of malaria increasingly difficult. In addition, many insecticides are no longer useful against the mosquitoes that transmit the disease. Crucell is working in collaboration with a number of research groups to develop a safe, effective and affordable vaccine against Plasmodium falciparum, the most lethal of the four species of malaria parasite that infect humans. Crucell s approach is based on our innovative AdVac technology, which uses novel, harmless adenoviruses as vaccine delivery vehicles (vectors). In April, 2010, Crucell entered into an agreement with GlaxoSmithKline Biologicals (GSK) to collaborate on developing a second-generation malaria vaccine candidate. Crucell is contributing the recombinant malaria vaccine candidate Ad35-CS, based on Crucell s PER.C6 and AdVac technologies, while GSK is contributing its late-stage malaria vaccine candidate RTS,S/AS. The collaborative partners aim to advance this new vaccine candidate into human clinical studies with the support of the PATH Malaria Vaccine Initiative (MVI). Clinical efficacy challenge trials sponsored by the MVI will be initiated in 2011 at the US Walter Reed Army Institute of Research, providing all agreements are finalized. Pending the results of these Phase I/IIa trials, Crucell and GSK expect to advance the prime boost candidate in further clinical studies with the support of public or non-profit partners who are interested in accelerating the development of a malaria vaccine. In May 2010, Crucell announced the start of a new Phase I clinical study in Burkina Faso, West Africa. Crucell is developing its malaria vaccine vector, Ad35-CS, in collaboration with National Institute of Allergy and Infectious Diseases (NIAID)/ National Institutes of Health (NIH), the Centre National de Recherche et de Formation sur le Paludisme (CNRFP) in Burkina Faso, and the Noguchi Memorial Institute for Medical Research at the University of Ghana. Enrolment has been completed and boost vaccinations are ongoing. This is the first study evaluating the safety and immunogenicity of this AdVac -based malaria vaccine vector candidate in a population living in a malaria endemic area. Ebola and Marburg (Phase I) Ebola and Marburg are among the world s most lethal viral diseases. Both Ebola and Marburg are among the few viruses causing hemorrhagic fever, a severe, often fatal disease in humans. There are currently no vaccines or antiviral therapies available for either disease. Crucell is developing a multivalent filovirus vaccine against Ebola and Marburg in collaboration with the Vaccine Research Center of the US National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). The candidate vaccine is based on Crucell s proprietary adenoviral vector technology and is produced using Crucell s PER.C6 technology.

18 16 Our business Research and development In August 2010, Crucell announced its participation in an international Phase I clinical trial in the United States and Africa of a combination of two AdVac -based AIDS vaccine candidates, Ad26.ENVA.01 and Ad35-ENV, in healthy adults who are not infected with HIV. The clinical trial, which will be led by the International AIDS Vaccine Initiative (IAVI), represents a collaboration between IAVI, Crucell, the Ragon Institute, and Beth Israel Deaconess Medical Center (BIDMC), a major teaching hospital of Harvard Medical School. In 2008, an estimated 2.7 million people were newly infected with HIV. Source: WHO. Every 17,5 seconds one person dies of AIDS. Source: Stop Aids Now! HIV (Phase I) Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immune deficiency syndrome (AIDS), a condition in which the immune system progressively fails, leading to life-threatening infections. Over the past 25 years, HIV infection resulting in AIDS has claimed millions of lives, devastated communities, and enormously frustrated efforts to fight poverty, improve global health and promote economic development. According to the 2010 Progress Report (a joint report by UNAIDS, Unicef and WHO), the HIV epidemic remains a major global public health challenge, with a total of 33.4 million people living with HIV worldwide. In 2008 alone, 2.7 million people were newly infected with HIV. The Ad26.ENVA.01 vaccine candidate used in this study is developed and manufactured by Crucell, while the Ad35-ENV vaccine is developed by IAVI. Both vaccines candidates are based on Crucell s proprietary AdVac technology. The planned Phase 1 trial of the vaccine combination represents a key step towards proof of concept studies to evaluate the efficacy of the vaccine combination in humans. HPV (Discovery/Pre-clinical) Genital infection with human papilloma virus (HPV) is very common in both men and women and usually spontaneously clears within one year after infection. In about 1% of individuals, however, HPV persists and ultimately results in genital neoplastic lesions. 1 Source: WHO, factsheet on rabies.

19 Our business Research and development 17 In November 2010, Crucell announced the start of a discovery program leading to the development and commercialization of a therapeutic HPV vaccine. The discovery program is part of a strategic collaboration, signed in September 2009 with Johnson & Johnson, through its subsidiary Ortho-McNeil-Janssen Pharmaceuticals, Inc., to develop innovative products, including antibodies for influenza prevention and treatment. RSV (Discovery/Pre-clinical) Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness in infants and children. RSV-induced disease is the last of the major paediatric diseases for which no preventive vaccine is available. Current prevention in developed countries is based on the administration of a costly RSV-neutralizing antibody, which is given to high-risk infants, in particular premature newborns. RSV also induces severe disease in immunocompromized adults and elderly people with weak immune systems, for whom the RSV antibody is not available. In June 2010, Crucell announced the start of a discovery program leading to the development and commercialization of a universal RSV vaccine. The vaccine will be designed to prevent severe infections with the most common RSV strains in infants and the elderly. This discovery program is part of a strategic collaboration with Johnson & Johnson, signed in September As an encouragement towards the RSV research community, Crucell sponsored the VII Respiratory Syncytial Virus Symposium held in December 2010 and established the Innovation Award for RSV Research. This support highlights Crucell s long-standing commitment to improve the health of people worldwide by advancing the fight against infectious diseases. Antibody development Antibodies are proteins made naturally by cells of the body s immune system. They function as one of the body s principal defense mechanisms against pathogens disease-causing agents such as parasites, viruses or bacteria. As antibodies recognize and bind to invading pathogens, ultimately eliminating them, they play a crucial role in protecting humans against disease. Rabies antibody combination (Phase II) Rabies is a viral disease of mammals and is most often transmitted through the bite of a rabid animal. The virus infects the central nervous system, causing encephalitis (inflammation of the brain) and ultimately death if appropriate medical intervention is not given promptly. Every year, more than 15 million people worldwide receive a post-exposure preventive regimen to avert the disease. This is estimated to prevent 327,000 rabies deaths annually. 1 Nevertheless, an estimated 55,000 individuals exposed to rabies virus mostly children die each year. Most of those who die receive a rabies vaccine only, rather than the proper post-exposure treatment consisting of anti-rabies antibodies as well as a vaccine. Concerns about the availability and safety of the current, blood-derived antibody treatment have prompted the search for a safe, effective and affordable alternative.

20 18 Our business Research and development Since January 2008, the route toward global availability of this next-generation, life-saving rabies biological has been facilitated by a strategic partnership between Crucell and sanofi pasteur, a world leader in rabies immunization. Under the terms of this agreement, Crucell will be responsible for manufacturing the commercial product and has retained exclusive distribution rights in Europe, co-exclusive distribution rights in China and the rights to sell to supranational organizations, while sanofi pasteur will have exclusive distribution rights for all other territories and co-exclusive distribution rights in China. A planned Phase II trial in India is expected to start in the first half of This study is designed to collect data on the safety and neutralizing activity of the rabies antibody combination plus vaccine in a simulated rabies post-exposure prophylaxis setting. An estimated 55,000 individuals exposed to rabies virus mostly children die each year. Source: WHO. Crucell scientists in collaboration with scientists from Thomas Jefferson University (TJU) in Philadelphia and the US Centers for Disease Control and Prevention in Atlanta, USA to discover a combination of human monoclonal antibodies (mabs) for the post-exposure treatment of rabies. Crucell s innovative MAbstract and PER.C6 technologies played a crucial role in the discovery and development of this promising therapy. The candidate mab product is designed to be used together with rabies vaccine. Preclinical studies conducted during 2004 indicated that the mab combination could neutralize (inactivate) rabies virus at least as effectively as blood-derived human rabies immune globulin (HRIG), the current gold standard for providing immediate protection against rabies virus. Since then, the rabies mab combination has successfully progressed through phase I clinical trials in the USA and India (in ) and phase II trials in the USA and the Philippines. The US Food and Drug Administration (FDA) has granted the rabies mab combination Fast Track status, paving the way for priority handling of the regulatory dossier. Human monoclonal antibodies against a broad range of influenza strains (Pre-clinical) Imagine a single product that could solve all the problems currently limiting influenza control. It would have to reliably protect all subgroups of the population especially the elderly against serious illness and death, regardless of the causal viral strain. Ideally, it would both prevent and cure influenza. In December 2008, Crucell announced the discovery of a new class of mabs with this extraordinary potential. Crucell also reported the results of preclinical studies involving a representative of this new mab class, CR6261. The antibody was shown to neutralize a broad range of influenza viruses, including the currently circulating H1N1 seasonal flu strains (genetic descendants of the virus responsible for 40 million deaths during the pandemic of ) and the highly pathogenic H5N1 ( bird flu ) virus. More recent tests have shown that CR6261 also combats the novel H1N1 virus that caused the 2009 pandemic. 1 Source: US National Library of Medicine, National Institute of Health.

21 Our business Research and development 19 In a pre-clinical study comparing CR6261 with the leading antiviral drug, oseltamivir, Crucell s mab strongly outperformed oseltamivir for influenza prevention and treatment. The study showed that CR6261 provides immediate protection against influenza viruses, suggesting that it will be able to prevent disease spread and therefore ward off a threatening pandemic. In contrast, oseltamivir was less effective and in some cases, not effective at all. In August 2009, Crucell obtained an exclusive license from Stanford University (Palo Alto, California) for the development of an antibody combination against HCV. A large panel of fully human mabs against HCV is being evaluated by Crucell in a proof of concept phase. The mabs have been found to neutralize the virus across all genotypes tested and each recognizes a different part of the HCV surface protein. In September 2009, Johnson & Johnson, through its subsidiary Ortho-McNeil-Janssen Pharmaceuticals, Inc., entered into a strategic collaboration with Crucell for the development and commercialization of a universal mab product (flu-mab) for the treatment and prevention of influenza. An important recent step in the development of this flu-mab has been the first production of this antibody product in a mobile and fully disposable FlexFactory. Universal influenza vaccine (Discovery/Pre-clinical) The exciting flu-mab research and development has laid the basis for the discovery and development of a vaccine that could protect against all subtypes of influenza virus. Hepatitis C antibody combination (Pre-clinical) Hepatitis C is a disease of the liver, caused by the hepatitis C virus (HCV). The virus can be transmitted by direct blood contact, for instance by sharing contaminated needles among drug users or by needle stick injuries in healthcare settings. Hepatitis C is a major global public health problem. A significant proportion of people (20 50%) develop progressive liver disease leading ultimately to liver cirrhosis, liver failure and hepatocellular carcinoma (HCC). 1 Most people who have been infected develop chronic disease. Symptomatic chronic HCV patients can be treated with antiviral agents (usually a combination of pegylated interferon and ribavirin), but with limited success. The only treatment option for end-stage liver disease is transplantation. HCV-induced cirrhosis is the leading cause for liver transplantation. It is estimated that up to 170 million people worldwide (3% of the world s population) are infected with HCV. There is no available vaccine against HCV.

22 20 Our business Technologies

23 Our business Technologies 21 Crucell s strong research and development (R&D) pipeline is supported by a range of patented technologies. Our technologies open up new areas of research, speed our development programs and optimize production processes. In this section you can read about our technologies and the way Crucell continues to extend their applications.

24 22 Our business Technologies Core proprietary technology platforms Crucell has five core proprietary technology platforms, and two support technologies developed by Crucell to facilitate biopharmaceutical innovation: Our cutting-edge technologies Crucell s strong product portfolio is supported by a range of patented technologies. Our cutting-edge technology platforms enable the cost-effective discovery, development and production of a range of biopharmaceutical products, including innovative vaccines, therapeutic proteins and gene therapies. In therapeutic areas where Crucell does not plan to develop its own products, these proprietary technologies may be licensed out to other biopharmaceutical manufacturers or research groups. 5 core platforms 1. PER.C6 technology: a comprehensive package of technology and know-how based on our PER.C6 human cell line. It provides a safe and cost-effective manufacturing system for high-yield, large-scale production of vaccines, recombinant proteins including monoclonal antibodies, and gene therapy products. 2. AdVac technology: a technology based on the development and production of novel adenovirus vectors. It can be used together with PER.C6 technology to develop recombinant vaccines against life-threatening diseases or to develop gene therapy products. 3. MAbstract technology: a human-based antibody phage display technology that facilitates the discovery of novel drug targets and the identification of human monoclonal antibodies against those targets. 4. STAR technology: a gene expression technology that enhances yields of recombinant human antibodies and therapeutic proteins on mammalian cells lines. 5. Virosome technology: a virosome is a virus-like particle that acts as a vaccine adjuvant and carrier system. Vaccines based on virosome technology combine high efficacy with high purity, and therefore low potential for causing side effects. Support technologies A. Recombinant Paramyxovirus technology: a novel vaccine design technology based on recombinant measles vectors. These vaccine vectors can be manufactured economically in large quantities, and induce strong and sustained immune responses against the antigens they carry. B. Hansenula polymorpha technology: an innovative yeast-based production platform widely used for the manufacture of industrial proteins, food and feed additives, and highly immunogenic vaccines such as Crucell s Hepavax-Gene vaccine against hepatitis B.

25 Our business Technologies 23 PER.C6 technology: an innovative package The PER.C6 human cell line is the cornerstone on which Crucell was built. It was originally developed for making antibodies against cancer and for gene therapy, but around 2002 researchers in the company discovered that a wide range of viruses also grow very well on PER.C6. This meant that PER.C6 could be developed as a platform for producing the new viral vaccines the world needs classical as well as adenovirus-based vaccines. PER.C6 technology offers major advantages over other platforms used for manufacturing biological products and is uniquely positioned to meet the key challenges in the industry. These include the need to produce larger volumes of product more quickly and cost-effectively, while meeting increasingly stringent safety requirements. The heart of PER.C6 technology is the PER.C6 human cell line. This is a continuously dividing set of cells derived from a single human cell, immortalized using recombinant DNA technology. Like other continuous cell lines, PER.C6 cells can replicate indefinitely but that is where the comparison ends. One of the great advantages of PER.C6 cells is that they grow to much higher density than other continuous cell lines. This is due to inherent characteristics of the PER.C6 cells themselves, which are further enhanced by the intensified manufacturing process and special growth media developed as part of the PER.C6 technology package. The ability of PER.C6 cells to grow to exceptionally high densities means that much more biological product can be harvested from much smaller bioreactors. For example, PER.C6 cells infected with virus for manufacturing purposes produce at least 10 times more virus per milliliter than any other cell line does. The same yield can therefore be obtained from a 500-liter bioreactor using PER.C6 as a 5000-liter or larger bioreactor using another cell line. This translates into significant savings in capital expenditure and production costs, as well as shorter production times. PER.C6 technology is an ideal companion for other innovative Crucell technologies, such as the virosome (a vaccine design technology combining high efficacy with low side effects) and AdVac technology (which focuses on the development of novel adenovirus vectors and is used with PER.C6 to develop recombinant vaccines). 27 g/l Record-level titer achieved at harvest for an antibody product using PER.C6 human cell line technology. 10 times More virus per millimeter are produced by PER.C6 infected cells.

26 24 Our business Technologies The PERCIVIA PER.C6 Development Center is designed to further develop the PER.C6 cell line and to provide turnkey solutions for licensees utilizing the PER.C6 human cell line to produce pharmaceutical proteins. PERCIVIA PER.C6 Development Center In September 2010, Crucell and Royal DSM announced the expansion of activities in their existing joint venture, the PERCIVIA PER.C6 Development Center (Cambridge, Massachusetts, US), to transform the company from a development center into a full biopharmaceutical company for the development of PER.C6 -based biobetter proteins and monoclonal antibodies as well as global licensing of the PER.C6 human cell line for production of third party monoclonal antibodies and other proteins. The joint venture, in which DSM and Crucell each hold an equal equity share, will be known as PERCIVIA LLC. The joint venture will broaden its scope and will focus on proprietary development of PER.C6 -based biobetter proteins and monoclonal antibodies, initially to early clinical stages. AdVac technology is a powerful vector system, especially when coupled with Crucell s PER.C6 technology, which unlike any other cell line does not allow replication-competent adenoviruses to form during the production of replication-deficient vectors. AdVac technology is based on adenoviruses that very rarely infect humans, whereas other adenovirus vectors are based on viruses that are widespread in human populations and therefore much more likely to encounter pre-existing immunity. By circumventing pre-existing immune responses against the adenovirus vector, AdVac -based vaccines allow accurate dose control and are potentially more effective than other adenoviral vector vaccines. AdVac -based vectors share the advantages of the widely used adenovirus vectors, such as scalable production, high yields and the ability to mediate a strong T-cell immune response. AdVac technology AdVac technology involves the development and manufacture of novel vectors (gene transport vehicles) made from adenoviruses (harmless cold viruses) that very rarely infect humans, such as Ad35. Genetic material encoding for viruses, parasites or bacteria can be inserted into these vectors to make novel vaccines against a broad range of human pathogens, or the vectors can be used to make gene therapy products.

27 Our business Technologies 25 MAbstract technology MAbstract technology is a human antibody-based phage display system, which facilitates the discovery of novel drug targets and the identification of human monoclonal antibody against those targets. A phage (or bacteriophage ) is a virus that can infect and multiply in bacteria. In phage display technology, phages are genetically engineered to expresses the pathogen-binding part of a human antibody on their surfaces. In the application of MAbstract technology, a library of phages exposing a wide variety of human antibody fragments on their surfaces is brought into contact with disease-causing microorganisms (pathogens) or parts of pathogens in order to identify human antibodies that selectively bind to targets of interest. MAbstract technology is an efficient method for the discovery of human antibodies to be applied for the prevention, diagnosis and therapy of diseases. STAR technology STAR technology is a gene expression technology. Acquired by Crucell in 2004, it has proved extremely valuable for increasing production of recombinant antibodies and therapeutic proteins on mammalian cell lines. STAR technology uses well-established mammalian cell banks for protein and antibody production, thereby eliminating the need for specially engineered mammalian cells. It allows for very rapid, stable mammalian cell clone generation and typically generates stable mammalian cell clones that produce 5 to 10 times more antibody or other therapeutic protein than cell clones generated without STAR technology. Virosome technology Virosome technology is a tool for developing novel vaccines against infectious and chronic diseases. A virosome is a virus-like particle that acts as a vaccine carrier and adjuvant (immunity enhancing) system. Vaccines based on virosome technology combine high efficacy with high purity, which means they are effective and safe to use even in infants and individuals with a weakened immune system.

28 26 Our business Products

29 Our business Products 27 Crucell focuses on developing and marketing vaccines and antibodies against a range of infectious diseases in the paediatric, travel and endemic, and respiratory fields. We currently have a product portfolio of vaccines against twelve major infectious diseases, such as influenza, hepatitis A, hepatitis B and typhoid fever.

30 28 Our business Products In this section, you will find information about Crucell s marketed products and comprehensive information about the diseases each of these vaccines is designed to prevent. Quinvaxem Our broad range of innovative products Vaccines play a vital role in protecting against disease and have contributed significantly to the improvement of global public health. Smallpox was eradicated through the use of vaccines. Significant advances include the introduction of combination vaccines and the development of new vaccine technologies. In 2010, a Crucell vaccine was given to 190 people every minute. 1 Over the full year, more than 105 million doses of vaccines were distributed in more than 100 countries, thereby preventing more than 3.6 million cases of infectious diseases and over 809, 000 deaths that would otherwise have occurred. 1 Figures based on Crucell s top 5 vaccines Quinvaxem, Hepavax-Gene, Epaxal, Vivotif and Inflexal V. Total 101,666,000 doses minus 2% waste (2,033,320 doses) = 99,632,680 doses sold in 2010 / minutes in 2010 = doses administered per minute. Quinvaxem fully liquid pentavalent (five-in-one) vaccine protects infants against five deadly childhood infections: diphtheria (D), tetanus (T), pertussis (P, whooping cough), hepatitis B (HepB), and Haemophilus influenzae type b (Hib). Combination vaccines help to simplify and harmonize vaccination schedules, leading to increased vaccine coverage and greater costeffectiveness. As the first fully liquid pentavalent DTwP HepB Hib vaccine brought to the market, Quinvaxem further simplified vaccine delivery because it is ready to use as soon as the vial is opened. This makes it an ideal choice for protecting babies in developing countries with infrastructure and hygiene problems. Quinvaxem remains the only fully liquid pentavalent vaccine that offers these advantages in a preservative-free formulation. Since the launch of Quinvaxem in 2006, over 200 million doses of this life-saving vaccine have been delivered to developing countries, including 50 GAVI-supported countries. Most were low-income countries supplied through Unicef and the Pan American Health Organization (PAHO). With this innovation, Crucell has become a major partner in protecting children in under-resourced countries.

31 Our business Products 29 Cases of disease prevented by Quinvaxem < 5,000 5,000 10,000 10, ,000 > 100,000 No report Hepavax-Gene 190 people Were given a Crucell vaccine every minute during mln Doses of vaccines were distributed in more than 100 countries in Hepavax-Gene is a recombinant vaccine against hepatitis B virus infection, providing long-term protection. With a track record of more than 800 million doses administered worldwide since the launch of this vaccine in 1997, it is also one of the established WHO pre-qualified vaccines. 3.6 mln Cases of infectious diseases were prevented in 2010.

32 30 Our business Products MoRu-Viraten Epaxal is approved for use in adults and children from 1 year of age. The vaccine is currently licensed in more than 35 countries under the brand names Epaxal, HAVpur and VIROHEP-A. Vivotif MoRu-Viraten is a safe, well-tolerated and effective vaccine for protection against measles and rubella in children, adolescents and adults. As MoRu-Viraten is free of egg proteins and antibiotics, it can be safely used in children with allergies to these substances. The vaccine has been marketed since 1986 and is on the WHO list of vaccines for purchase by UN agencies. Epaxal and Epaxal Junior Vivotif is a live attenuated oral vaccine for immunization of children and adults against typhoid fever. It is available as gastro-resistant capsules for oral administration. It is the only oral vaccine approved for protection against typhoid fever. The most common cause of this bacterial disease is Salmonella serotype Typhi (S. Typhi). The protective action starts about 10 days after the last dose is taken. Vivotif is remarkably well tolerated, with post-marketing experience over more than 20 years confirming that adverse events are rare. Vivotif typhoid fever vaccine is currently licensed in more than 30 countries, including the United States. Dukoral Virosomal adjuvanted Epaxal is the only aluminum-free hepatitis A vaccine on the international market. The absence of aluminum reduces the pain associated with injection, making this vaccine especially suitable for children. A virosome is a biodegradable adjuvant system and provides a more natural presentation of the antigens than traditional adjuvants. Epaxal induces protective antibody levels within 10 days after the initial injection. A second dose prolongs effective protection for an estimated 30 years or more. The booster dose is preferably injected 6 12 months after the first dose but may be given up to 10 years later. Dukoral oral inactivated cholera vaccine provides safe, effective and convenient protection against cholera for people living in at-risk

33 Our business Products 31 areas as well as visitors to these regions. Outbreaks of severe disease in regions where cholera is endemic put local populations at risk of serious illness and death. Travelers diarrhea caused by cholera is generally not life-threatening but is distressing and debilitating, spoiling many holidays and business trips. This preventable diarrheal infection is now the most common travel illness but remains an under-recognized problem. Dukoral was first licensed in 1992 and is now registered in 65 countries for the prevention of cholera, with additional indications (ETEC, travelers diarrhea) in some of these countries. It is an oral inactivated vaccine approved for use in adults and children from two years of age. Dukoral drinkable vaccine is easy to use and offers 84 86% protection against cholera, as demonstrated in field clinical trials on various continents. Dukoral also has a reassuringly favorable safety profile, with an adverse event rate comparable to placebo reported in clinical trials. The vaccine s safety and tolerability has been confirmed over many years of use around the world. Inflexal V Inflexal V virosomal adjuvanted vaccine offers protection against influenza thanks to its virosome technology one of Crucell s patented innovations. Virosomes are reconstituted influenza virus envelopes, constructed without the genetic information of the virus so that they are unable to replicate or cause infections. In the context of vaccines, virosomes serve as both a carrier system and an adjuvant. Inflexal V is the only adjuvanted influenza vaccine licensed for all age groups (from 6 months upwards). Since its launch in 1997, Inflexal V has been licensed in 38 countries with over 60 million doses distributed. Extensive experience in the market has confirmed its efficacy and favorable safety profile. The vaccine s unique design and manufacturing process eliminate the need for thiomersal (a vaccine preservative) or formaldehyde (commonly used to inactivate influenza viruses) and minimize residual traces of antibiotics, detergent and hen s egg protein compared with other influenza vaccines. The vaccine s antigen composition changes in accordance with annual recommendations issued by the World Health Organization (WHO) on the basis of data on the circulating influenza virus strains. Other products We also distribute a variety of other products, such as Gardasil (Merck) and Prolastin (Talecris).

34 32 Crucell s commitment to the world Taking responsibility

35 Crucell s commitment to the world Taking responsibility 33 Crucell s mission to bring innovation to global health reflects a deep commitment to improving the lives of people worldwide. We see this as part of our corporate social responsibility (CSR) a responsibility that underpins everything we do as a global organization and as individuals united by a common purpose. For several years we have been working to develop our approach to CSR, with the goal of maximizing our contribution to society and minimizing our environmental impact. This report highlights the recent steps we have taken on our journey and outlines the road ahead.

36 34 Crucell s commitment to the world Taking responsibility Taking responsibility for a better world Crucell is making great strides with the implementation of a comprehensive policy for integrating sustainability practices in our organization. In 2009, we outlined our CSR 4P policy framework incorporating the four Ps of Performance, People, Planet and Philanthropy. In 2010, we focused on bringing this policy to life in our global organization, with substantial success. A first step in this process was to establish a CSR Working Group, which is responsible for driving continuous progress in the four P-categories. With strong support from Crucell s Management Board and many Crucell employees worldwide, this group has risen to the challenge of introducing a consistent approach to CSR development, information management and reporting. Despite the complexity of harmonizing data and definitions across departments and sites, close to full data coverage has been achieved. This will enable us to measure our progress and further improve both target setting and reporting in the years ahead. At the same time, we have been seizing opportunities for increasing our contribution to society right here and now. The rapid evolution of Footprint, our community outreach program, is one exciting example of this. The introduction of global learning and development programs for Crucell employees is another. Wherever possible, we have achieved quick wins regarding our environmental impact, while working towards a more comprehensive approach in the longer term. Looking to the future, we are delighted that talks we held with Johnson & Johnson during 2010 have resulted in Crucell becoming the center of excellence for vaccines within the world s largest and possibly most respected healthcare company. As a member of the Johnson & Johnson Family of Companies, we can do so much more to make the world we live in a healthier and safer place. This is our core business, our passion and a key component of our CSR program. On the threshold of this new era, we have compiled this report in order to update our stakeholders on the current status of our CSR program, the contribution we made to society during 2010 and our plans for the future. About this report The information in this report covers the global Crucell organization during the full calendar year 2010, unless otherwise stated. Crucell has not sought external verification of the information presented here as our current priority is to facilitate the smooth working of our newly implemented systems for CSR development. Contents CSR highlights in Our CSR policy 36 Performance 40 People 51 Planet 58 Philanthropy 62 Appendix 70

37 Crucell s commitment to the world Taking responsibility 35 CSR highlights in 2010 y A CSR Working Group was established in the first quarter of 2010 and has driven the implementation of Crucell s global policy for evidence-based CSR development and reporting. y The initial set of ambitions, targets and key performance indicators in the CSR 4P framework categories of Performance, People, Planet and Philanthropy have been reviewed, revised and expanded where necessary. y A centralized system for CSR information management has been developed and rolled out worldwide, and company-wide data collected for baseline assessments. y For the second successive year, Crucell was listed on the Dow Jones Sustainability Index (DJSI) in 2010 and showed strong progress on the Dutch Transparency Benchmark. y Crucell CEO Ronald Brus was nominated by the vaccine industry of industrialized countries to represent the constituency on the Board of the GAVI Alliance, a public-private partnership dedicated to improving access to new and underused vaccines in the world s poorest countries. y Hundreds of talented people were recruited and further operational improvements were made in order to boost Crucell s capacity to bring innovation to global health. y A range of global initiatives were launched to foster employees learning and development, which has been identified as the CSR priority with respect to human resources. y Crucell made important advances towards responsible supply chain management. y Crucell partnered the International Pediatric Association, the nongovernmental organization (NGO) Friendship and other organizations in their great efforts to support national vaccination programs in developing countries, as well as other NGOs such as the Max Foundation. y Footprint, Crucell s community outreach program, expanded in scope and impact. Two field trips made an indelible impression on the lives of participating employees from different Crucell offices around the world, as well as the people living in disadvantaged communities in South Africa and Bangladesh. y The success of Crucell s collaboration with Johnson & Johnson on research and development (R&D) projects during 2010 prompted both parties to explore the possibility of closer ties. This led to Crucell joining the Johnson & Johnson Family of Companies in February 2011, in what we see as an exciting advance for world health. Our CSR program is a concerted effort to ensure that we maximize the benefits we bring to society while minimizing our environmental footprint.

38 36 Crucell s commitment to the world Taking responsibility Our CSR policy Because we care To protect, care for and contribute to society in the fullest possible sense and to the best of our ability: that is the essence of Crucell s CSR policy. These principles of protection, care and contribution are a logical extension of our mission to bring innovation to global health, focusing especially on the prevention of infectious diseases. Crucell s core business is the discovery, development and delivery of innovative solutions for major health threats. Our specialty is the creation of much-needed immunization products: vaccines that safely and effectively mobilize the body s own immune defenses against infections, and antibodies that provide ready-made immune protection against invading microbes. After clean water, immunization is believed to be the most cost-effective health intervention and its key role in promoting the socioeconomic development of countries is becoming increasingly clear. The world population is predicted to reach 7 billion in 2011 and protecting these billions of individuals from infectious diseases is more important and challenging than ever. Trends such as climate change, globalization, urbanization, wider travel and population aging are presenting new opportunities for infectious pathogens to thrive and spread. Doing our utmost to tackle this problem is our primary responsibility and our privilege. It lies at the heart of our approach to CSR. At the same time, we recognize that Crucell as a global business with many stakeholders has wider social responsibilities. As our business expands in line with our ambitions, our impact on the world around us will increase. Our CSR program is a concerted effort to ensure that we maximize the benefits we bring to society while minimizing our environmental footprint. Achieving the optimal balance is a challenge that calls for a proactive approach and ongoing, careful evaluation of our activities and their effects. Our stakeholders Crucell works to bring significant benefit to the lives of people worldwide. This requires constructive interaction with a large number of stakeholders, including employees, legislators, investors, policy makers, business partners, licensees, suppliers, customers and organizations dedicated to sustainability issues. Our external stakeholders are far too numerous to mention, but in the interests of transparency here is a shortlist of key examples. y Legislators: US Food and Drug Administration, European Medicines Agency, and national regulatory authorities. y Policy makers: World Health Organization (WHO), Pan American Health Organization (PAHO), GAVI Alliance. y Business partners: Johnson & Johnson, DSM Biologics, Merck, Novartis, sanofi pasteur, Wyeth and MedImmune. y Customers: Supranational purchasing organizations such as Unicef (on behalf of developing countries); public and/or private health organizations in developed countries. y Sustainability organizatons: Dow Jones Sustainability Index, Carbon Disclosure Project. Stepwise progress Crucell sees CSR development as a continuous process and aims for steady progression. When we launched our global CSR program in 2008, our priority was to raise awareness and support for this initiative throughout our own organization, as well as starting a dialogue with our external stakeholders about our ambition to focus more on CSR performance and transparency. In 2009, we made the transition from this ambition to a strategy for CSR development, and outlined the 4P framework for a global CSR policy (see page 40) based on the four categories of Performance, People, Planet and Philanthropy. An initial set of ambitions, targets

39 Crucell s commitment to the world Taking responsibility 37 and key performance indicators (KPIs) was formulated for each category. Of these, five were earmarked for special effort: CSR information management improvement, transparency objectives, responsible supply chain, CO 2 footprint and water use. Ambitious longer-term objectives were set for several of these indicators (see table 1). In 2010, we embarked on the implementation of our global CSR policy, including the roll-out of systems that will enable us to monitor, evaluate and improve our CSR performance and report on this in a transparent way. To protect, care for and contribute to society in the fullest possible sense and to the best of our ability: that is the essence of Crucell s CSR policy. Table 1: Crucell s top-five ambitions for CSR development KPI Target achieved in 2010 Target for 2011 Target for longer term CSR information management improvement Roll out Reporting Manual Report based on 100% company coverage Set action plans for long term and set Define in 2011 quantitative targets for EHS 1 Transparency objectives Remain in DJSI 2 Improve CSR web page Further improve CSR web page and continue to develop reporting practices 2015: GRI 3 A rating Responsible supply chain Extend global procurement policy Train all relevant employees 80% of top 100 vendors sign Supplier Code of Conduct (CSR declaration) and take part in CSR assessment Monitor and maintain training level 100% supplier coverage and monitoring of target group in 2011 CO 2 footprint Baseline setting Quantitative ambition setting 2020: 15% relative reduction 4 Water use Baseline setting (100% company coverage) Quantitative ambition setting 2020: 10% relative reduction 4 1 EHS environment, health and safety. 2 DJSI Dow Jones Sustainability Indexes. 3 GRI Global Reporting Initiative. 4 Relative to workforce size expressed in full-time equivalents.

40 38 Crucell s commitment to the world Taking responsibility The 4P framework of Crucell s CSR Policy Performance Saving lives Innovation Responsible supply chain Transparency Emissions to air Emissions to water Consumption Recycling Planet People Responsible employer Health & safety Business conduct Sector sustainability initiatives Contributing to science Access to healthcare NGO partnerships Community outreach Philanthropy Clarity and leadership Crucell s CSR policy 4P framework (see left) summarizes the main ways we strive to make a positive difference to society: y by performing at our best as a business dedicated to healthcare innovation; y by taking the best possible care of the people we work with, inside and outside the company; y by doing whatever we can to preserve and protect the earth s precious resources; y and by contributing even more than we are required to do as a company with an intrinsically CSR-oriented mission. The four categories of Performance, People, Planet and Philanthropy are each further subdivided into a variety of themes, which represent a range of related responsibilities. Themes can be added over time to reflect our evolving responsibilities, as this is a dynamic framework. This classification system is somewhat artificial, as there is considerable overlap and interdependence among the P-categories and their component themes. However, it serves as a useful reminder of the many different facets of our CSR strategy and provides a clear overview of what we, as a socially responsible company, stand for and strive towards. A practical advantage of the 4P framework is that it breaks the enormous task of CSR development and reporting into manageable portions. Early in 2010, one or more leaders ( P-owners ) were appointed for each P-category. They have taken real ownership for progress in their area, providing crucial inspiration and direction as well as coordinating the flow of information. This approach fosters transparency, clarity and focus, which helps the P-owners in consultation with top-level management to define realistic but challenging targets for the coming years. This step is vital for achieving the continuous progress we strive for and ensuring that our CSR strategy delivers tangible benefits for society. Adding real value is our goal.

41 Crucell s commitment to the world Taking responsibility 39 Organization and governance A CSR Working Group comprising the P-owners and several Crucell employees with a special advisory role was established in the first quarter of It is a diverse group of senior managers representing a wide range of disciplines and different Crucell sites. Members of the CSR Working Group gather information from all levels and parts of the organization. They also initiate improvements with support and advice from the Management Board. Overall ownership of CSR has been taken on by Chief Executive Officer Ronald Brus, ensuring top-level support for its ongoing development. The CSR Working Group meets on a quarterly basis to discuss progress and formulate plans for the future. Cees de Jong, Crucell s Chief Operating Officer, chaired these meetings in 2010 and reported on their outcomes at meetings of the Management Board. This participation reflects the importance Crucell s top management places on CSR, and ensures governance of the program at Management Board level. Bringing our CSR policy to life While strong leadership is essential for driving our CSR program, its success will depend on how firmly it can be embedded in the fabric of our organization and brought to life. That was our priority over the past year. In the next section of this report, we focus on each of the P-categories in turn, describing our current level of achievement, the actions undertaken in 2010, our progress relative to the targets and ambitions formulated in 2009, and our priorities for the future.

42 40 Crucell s commitment to the world Taking responsibility Performance The P-category we call Performance embraces four social responsibilities that we see as being central to our core business and our mission: innovation, saving lives, responsible supply chain management and transparency, by which we mean the responsibility to evaluate and report on our CSR activities in a comprehensive and systematic way. Transparency is, of course, an overarching principle in our CSR program and applies equally to all categories in the 4P policy framework. We have chosen to include it in the category most closely allied with our core business because we see transparency as a tool for strategic decision making, as well as a key responsibility towards our stakeholders. As a company dedicated to making a meaningful difference to people s lives, we want the fullest possible understanding of our impact on society and our planet. Under the leadership of the Performance P-owner, whose function in the organization is Director Global Procurement, a large number of Crucell employees have contributed to the gathering and analysis of information relevant to the initial set of key performance indicators (KPIs), targets and ambitions that were defined for this P-category in 2010 (see table 2). The P-owner s expertise in the field of Procurement was especially valuable for developing a strategy for responsible supply chain management, which is one of five KPIs for which we have set particularly ambitious objectives. Besides a responsible supply chain, the other KPIs we have selected to measure our contribution in the Performance category are: prevention of illness and deaths, the number of pipeline products, research and development (R&D) expenses, animal welfare, CSR management improvement, and transparency objectives (relating to benchmarks such as the Dow Jones Sustainability Index, the Carbon Disclosure Project and the Transparency Benchmark). These indicators form the basis of the following discussion of activities and outcomes in the Performance category during Saving lives During 2010, Crucell delivered 105 million doses of vaccines to people around the world, with the majority going to infants in developing countries. Together, the vaccines we have on the market prevent twelve major infectious diseases: childhood infections, travel and endemic illnesses, and respiratory disease. Allowing for the fact that some vaccines inevitably go to waste, we can estimate that a Crucell vaccine was given to 190 individuals every minute during a thought that makes us proud. However, we believe that the best measure of our impact on global health is not the number of doses we supply, but the number of deaths and cases of disease we prevent each year. In other words, how many people would have become sick or died if they had not received our vaccine? This can be estimated by combining sales figures with data on vaccine efficacy (how well a vaccine works), disease incidence (the expected number of new cases in a population) and case fatality (the death rate among infected patients). Based on the best available evidence for these parameters, and assuming a 2% vaccine waste rate, Crucell s top-five vaccines prevented more than 3.6 million cases of infectious disease and 809,823 deaths in This was similar to our health impact in 2009, when we prevented more than 3.6 million cases of disease and over 819,000 deaths. We did not meet our target of continuous improvement in the prevention of illness and deaths, as overall product sales were slightly lower in 2010 than Higher sales of travel and endemic vaccines were more than offset by lower sales of our seasonal influenza vaccine (due to the limited availability of flu antigen and weaker overall demand) as well as the temporary suspension of Quinvaxem shipments, as explained on page Figures based on Crucell s top 5 vaccines Quinvaxem, Hepavax-Gene, Epaxal, Vivotif and Inflexal V. Total 101,666,000 doses minus 2% waste (2,033,320 doses) = 99,632,680 doses sold in 2010 / minutes in 2010 = doses administered per minute. 2 Figure based on Crucell s top five vaccines in terms of sales volumes: Quinvaxem, Hepavax-Gene, Epaxal, Vivotif and Inflexal V.

43 Crucell s commitment to the world Taking responsibility 41 Innovation While we are already preventing an estimated 3.6 million cases of infectious disease and saving over 809,000 lives with our existing portfolio of marketed vaccines, we want to do much more. Ongoing innovation is the key to realizing this ambition. Crucell s broad research and development (R&D) pipeline currently includes twelve investigational products, of which nine are candidate vaccines and three are antibody-based immunization products. All are based on Crucell s innovative proprietary technologies, which provide unique opportunities for combating major threats to human health. These threats include some of the world s most powerful and elusive killers, such as tuberculosis, HIV/AIDS and malaria. The first two were responsible for 1.7 and 1.8 million deaths, respectively, in 2009, while malaria affected 225 million people in 2009 and claims almost one million lives annually. These enormous numbers highlight the importance and urgency of our promising vaccine research in these disease areas. Table 2: Performance KPIs and targets going forward KPI Quantitative/Qualitative Target Prevention of illness and death Continuous improvement Number of pipeline products Report annually Report annually Animal welfare Continuous improvement 3Rs 1 R&D expenses Report annually CSR information management improvement 2011: Set action plans and set quantitative targets for EHS 2 Responsible supply chain 2011: Train all relevant employees in responsible supply chain management 2011: 80% of top 100 vendors sign Supplier Code of Conduct (CSR declaration) and take part in CSR assessment Beyond 2011: Full coverage and monitoring of supplier target group Transparency objectives 2011: Further improve CSR web page and continue to develop reporting practices 2015: GRI 3 A rating 1 3Rs Reduce, Refine and Replace. 2 EHS Environment, health and safety. 3 GRI Global Reporting Initiative. Quantitative Qualitative

44 42 Crucell s commitment to the world Taking responsibility In the influenza field, our research teams are working on a trio of programs aimed at registering a better seasonal flu vaccine by 2014 and developing products that will revolutionize the approach to influenza prevention and treatment in the longer term. Influenza currently kills an estimated 345,000 people annually and imposes a heavy burden on society in terms of lost productivity and healthcare costs. The emergence of a lethal influenza virus with pandemic potential could push the death toll into tens of millions. For the 55,000 people especially children who die of rabies each year, we are developing a monoclonal antibody (mab) product in partnership with sanofi pasteur. People who are bitten by a rabid animal can be saved by immediate injection of rabies antibodies and vaccine, both of which exist, but the blood-derived antibodies now available are in short supply and too expensive for most developing countries, where the need is greatest. Our rabies mab product is poised to enter a large Phase II clinical trial in India in the first half of 2011, after showing very promising results in other clinical settings and populations. These are just some examples of the ways in which Crucell is working on medical solutions that really matter. A full overview of our pipeline products is given on page 13, and more information is available on the R&D section of our website. Animal welfare Before any candidate medical product can be given to humans, it must be rigorously tested in pre-clinical (non-human) models. Crucell performs animal testing to the minimum extent that is required by law. We conduct essential safety studies in animals in accordance with the highest international standards, which are designed to prevent or minimize any suffering of the animals tested. Simultaneously, we apply the 3R principles Reduce, Refine and Replace to pre-clinical studies involving animals. Crucell has been working over many years to replace animal tests with cell-based assays, and these efforts have already resulted in the significant reduction of animal testing mln Research and development investment in 2010 compared to 70.2 mln in Crucell invested heavily in the advancement and expansion of pipeline programs in

45 Crucell s commitment to the world Taking responsibility 43 R&D progress Crucell invested heavily in the advancement and expansion of pipeline programs in In line with our guidance to the financial market, R&D expenses increased by more than a third to million, compared to 70.2 million in The rise was predominantly due to an increase in clinical development spending, reflecting progress in clinical trials and significant investments in our in-house product development capabilities. Development of our pipeline during 2010 was accelerated by a strategic collaboration with Johnson & Johnson, signed in September Under the terms of this agreement, Johnson & Johnson will finance a significant part of Crucell s existing R&D program aimed at discovery, development and commercialization of a monoclonal antibody product for the universal prevention and treatment of influenza. This program is based on Crucell s discovery of a new class of antibodies with the unprecedented ability to neutralize a broad range of influenza virus strains. The strategic collaboration also provided funding for four new discovery programs in areas where Crucell s innovative science and technologies show significant potential to make an important difference to global health. One of these was specified at the time the agreement was signed, and two others were decided jointly by the collaboration partners on the basis of exploratory work by Crucell s Innovation & Discovery Laboratory (I&DL) teams in the course of In the first of the new discovery programs, Crucell scientists are using the knowledge generated in our flu antibodies program to design a vaccine with the potential to provide lifelong protection against influenza, regardless of the causal virus strain. A universal flu vaccine would eliminate the need to formulate new flu vaccines year after year, and would at last provide a defense against a lethal new influenza virus with pandemic potential. Work started on this exciting project at the beginning of The second discovery program, launched in June, focuses on the design of a vaccine to prevent severe respiratory infections caused by all of the most common strains of respiratory syncytial virus (RSV). Infants and the elderly are especially vulnerable to life-threatening illness caused by RSV, which currently claims an estimated 160,000 lives annually. RSV-induced disease is the last major childhood illness for which no preventive vaccine is available. The third new discovery program, announced in November, targets the development and commercialization of a therapeutic vaccine against human papillomavirus (HPV). Around 250,000 men and women with chronic HPV infection die each year. Another R&D highlight during 2010 was the launch of Crucell s in-house FluCell program: a new frontier for seasonal influenza vaccines. Inflexal V, our current flu vaccine, is both highly effective and very well tolerated thanks to its underlying virosomal technology. Now we are working to combine this innovative approach to vaccine design with our highdensity PER.C6 cell based production system. This will enable us to manufacture unlimited supplies of high-quality flu vaccine more efficiently, more cost-effectively and starting earlier in the flu season. The traditional production method grows the viruses used for flu vaccines in chicken eggs a slow and laborious method that does not lend itself to high-volume manufacturing, as we saw during the recent pandemic. The fact that we now have three influenza programs in the pipeline illustrates Crucell s approach to innovation. We seize opportunities to make a difference in the near future while simultaneously working towards breakthrough products that will take considerably longer to develop, test and bring to market. Investigational vaccines we already have in clinical trials made important progress during For example, in May the recombinant malaria vaccine Crucell is developing in collaboration with the US National Institute of Allergy and Infectious Diseases entered a new phase I trial in Burkina Faso, Africa. This is the first trial of the vaccine in a population living in an area where malaria is endemic. In October, we were delighted to announce the start of a new phase II clinical trial of the tuberculosis vaccine we are developing together with the Aeras Global TB Vaccine Foundation. The trial will evaluate the safety and efficacy of this promising vaccine candidate in infants previously immunized with Bacille Calmette Guérin (BCG) vaccine. BCG is the only available TB vaccine, but has very limited efficacy.

46 44 Crucell s commitment to the world Taking responsibility Prototype Uniject device Quinvaxem in Uniject : simply better Crucell has embarked on a development project that will make Quinvaxem pentavalent vaccine available in Uniject, an innovative vaccine injection system. The nonprofit organization PATH developed Uniject over 20 years ago with the aim of simplifying vaccine delivery, which the World Health Organization (WHO) sees as a key strategy for helping developing countries to improve their national immunization programs and reach populations in remote areas. The Uniject device is essentially a small plastic bubble attached to a fine, short needle and fitted with an auto-disable mechanism so that it can be used only once. The bubble will be filled with a single dose of Quinvaxem at Crucell s new manufacturing facility in Korea, where a state-of-the-art filling and inspection line will be created for this purpose. From there, the factory-filled devices will be shipped to the growing number of countries that are choosing Crucell s five-in-one vaccine to protect their children against diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type B (Hib), a leading cause of severe pneumonia and meningitis. Because the Uniject device needs no assembly or preparation in the field, it is ideal for countries with limited healthcare resources and a poor infrastructure. It is much faster and easier to use than the standard needle and syringe system, delivering the correct vaccine dose with a simple squeeze of the bubble. Medical staff can therefore administer more vaccines during an immunization session, with less risk of error, and even non-traditional healthcare workers can safely administer the vaccine after a short training. The auto-disable feature is important for preventing the spread of HIV and other infectious diseases. Uniject also reduces the vaccine wastage associated with multi-dose vials. Finally, its light weight and compact size facilitate transport to hard-to-reach areas. These benefits are proven, as Uniject has already been used to deliver hepatitis B and tetanus vaccines to over 73 million women and children in developing countries. Beckton- Dickinson (BD), with whom Crucell collaborates on the Uniject project, continues to further develop and improve the device. Crucell s commitment to the Uniject project reflects the breadth of our efforts to bring innovation to global health. We know that improving access to lifesaving vaccines depends on programmatic innovations as well as new vaccines. Crucell developed Quinvaxem to meet the specific immunization needs of the world s poorest countries, where delivering the WHOrecommended package of vaccines to all children under five is a major challenge. When it was introduced in 2006, the only other available pentavalent vaccine came in two vials and had to be reconstituted in the field. The Quinvaxem fully liquid formulation simplified vaccine delivery because it is ready for use as soon as the vial is opened. Putting Quinvaxem into Uniject will make delivery simpler again, further improving vaccine coverage and cost-effectiveness. The introduction of one of the key EPI 1 vaccines in BD Uniject also brings environmental advantages: no need for separate transport of syringes and vials, ease of disposal and reduction of toxic substance emissions during burning of waste. This development is the next logical step in an ongoing process of innovation. PATH is thrilled that Crucell is making this significant commitment, Steve Brooke from PATH told key opinion leaders at the International Pediatric Association (IPA) Congress in South Africa last August. Crucell announced its Uniject plans at the conference and invited feedback from potential users. This followed a meeting of the WHO group focusing on new and underutilized vaccines implementation (NUVI) in June, where stakeholders were surveyed on the benefits and constraints for pentavalent vaccine in Uniject. The WHO consultation at Technet, which explores technological innovations, provided another opportunity for dialogue and debate in December. Participation in such meetings helps us to understand and meet local needs, for example regarding packaging. 1 EPI stands for Expanded Program on Immunization, the WHO strategy for making vaccines available to all children worldwide.

47 Crucell s commitment to the world Taking responsibility 45 Recruitment and operational improvements in our R&D groups were a high priority during Dr Jerald Sadoff, a veteran of vaccine development and former director of the Aeras Global TB Vaccine Foundation, joined Crucell as Chief Medical Officer & Head of Development in March He brings with him a wealth of experience and enthusiasm to take Crucell s pipeline products to market in the shortest possible time. While working on the discovery and development of new vaccines and antibody products, Crucell also invests in programs that will increase the value and reach of existing products. A prime example of this sort of lifecycle development is our project to make Quinvaxem available in Uniject, an ingenious vaccine delivery device designed to meet the immunization needs of developing countries (see box). Other examples are our efforts to launch Epaxal hepatitis A vaccine on the US market and our R&D program to add a sixth vaccine to the Quinvaxem combination. Success and setback A total of 68.9 million doses of Quinvaxem vaccine, Crucell s lead product, were delivered to developing countries in 2010, compared to 64.3 million in Quinvaxem is a fully liquid pentavalent (five-inone) vaccine that protects against five major childhood diseases. It was developed specifically to meet the needs of countries with limited resources and is making a major contribution towards achieving the United Nations Millennium Development Goal of reducing the mortality rate among children under five by two-thirds between 1990 and In 2010, Vietnam joined the growing number of recipient countries after the Vietnamese health authorities registered Quinvaxem for use in the national immunization program. The first shipment was sent to Vietnam in April 2010 a month in which we shipped a record number of Quinvaxem doses. Fill and finish operations started at our new Korean production facility mid Quinvaxem vaccines sold (Doses in million units)

48 46 Crucell s commitment to the world Taking responsibility During 2010 we made excellent progress on the project to relocate Crucell s Korean production facility from the Shingal site in Yongin City to the Incheon Free Economic Zone. Operational testing of the Incheon production facility began in March 2010 and progressed rapidly from simulated test runs to validation testing of the real production process, which generates data on product consistency for submission to the regulatory authorities. These consistency runs have been completed successfully and we expect to receive regulatory approval of the Incheon facility in the second half of With a capacity of over 100 million doses annually, the new facility will enable us to significantly increase production volumes and efficiency in order to meet anticipated further growth in demand for Quinvaxem pentavalent vaccine and our hepatitis B vaccine Hepavax-Gene, which is also produced in Korea. Unfortunately, this success was followed by a setback later in the year. Despite our stringent quality and safety procedures, a microbiological contamination occurred at the Shingal plant in Korea where we manufacture Quinvaxem, leading us to temporarily suspend all shipments of vaccines from this facility at the end of October 2010 and launch a thorough investigation. Shipments of noncontaminated stock of Quinvaxem were resumed in December Full-scale commercial production of the vaccine recommenced at the Shingal facility at the start of February 2011, after the Korean regulatory authorities inspected the plant and declared it to be safe. This experience emphasizes the challenges and dilemmas inherent in our industry. Suspending the delivery of lifesaving vaccines as a precautionary measure was a painful choice and had significant financial consequences, but the alternative was unthinkable. We are not prepared to accept the slightest risk that a Crucell vaccine could cause harm. A new era The landmark event of 2010 was Johnson & Johnson making a recommended cash offer to acquire Crucell N.V. at a price of per share. The offer was formally made on 8 December 2010, and was declared unconditional on 22 February 2011, after more than 95% of the issued and outstanding share capital of Crucell was tendered for the offered price. The agreement makes Crucell the center for vaccines within the Johnson & Johnson Family of Companies, ushering in an exciting new era for our organization and above all for human health. We are delighted by the prospect of pursuing our mission with the support of Johnson & Johnson, an organization that shares our passion for healthcare innovation, our values and our commitment to care for people. We are an excellent fit and together we can make a much greater difference to the lives of people worldwide, says Crucell s CEO Ronald Brus. Johnson & Johnson is fully committed to investing in Crucell in order to accelerate our programs. What s more, its management clearly values and wants to foster Crucell s innovative and entrepreneurial spirit. This trust and respect is the key to a successful relationship.

49 Crucell s commitment to the world Taking responsibility 47 Responsible supply chain Responsible supply chain management was identified in 2009 as one of five priority areas for CSR development. Crucell wants to make sustainability issues an integral aspect of our choice of suppliers and our relationship with them, and we have charted a clear course towards this goal. The progress made in 2010 well exceeds our expectations. In 2009, we laid the basis for active management of our supply chain, from a CSR perspective, by professionalizing our procurement organization and introducing a global procurement policy. The main target set for 2010 was to incorporate industry best practices for responsible supply chain management, as defined by the Pharmaceutical Supply Chain Initiative (PSCI), into our procurement policy and practice. Rather than simply reproducing the PSCI best practices in Crucell s procurement guidelines, a team led by Crucell s Global Procurement director has developed a Suppliers Code of Conduct focusing on the PSCI principles that are most important and relevant for Crucell and our vendors. This Code is a declaration of Crucell s commitment to sustainability and what we expect of our suppliers. It is designed to encourage dialogue with suppliers, instead of a checklist or compliancy mentality. For this reason, the Code incorporates Crucellspecific ambitions relating to sustainability as well as guidelines for best practice. Working together Over the past year, this focus on dialogue has become central to our vision and strategy for responsible supply chain management. We want to engage our suppliers in an open conversation about sustainability practices, challenges and opportunities. By sharing our experiences and working together, we believe we can help the organizations that supply us with goods and services to make CSR improvements that benefit Crucell and ultimately, of course, our planet. Good things come in small packages During 2010, a multifunctional team at Crucell worked together with suppliers on a project to deliver our pentavalent paediatric vaccine Quinvaxem in smaller glass vials. The new vials contain the same volume of vaccine and are made of the same glass as before, so this change raises no regulatory or health issues. Each vial is 1 gram lighter and we expect to fit 17% more vials in the containers used for shipping. This significantly reduces energy used for transportation and makes more efficient use of the cold chain, which in developing countries is particularly limited. Smaller vials also mean less raw material and less waste. The wide range of benefits associated with this development highlights the breadth of Crucell s CSR efforts and the overlap among the 4P categories. We will start shipping Quinvaxem in the new vials in September With a capacity of over 100 million doses annually, the new facility will enable us to significantly increase production volumes and efficiency in order to meet anticipated further growth in demand for our Quinvaxem pentavalent vaccine and our hepatitis B vaccine Hepavax-Gene, which is also produced in Korea. Two new initiatives were launched in 2010 to foster the kind of dialogue and improvements we aspire to. One focuses on supplier assessment, the other on supplier participation in Crucell-led efforts to promote good sustainability practices in line with our CSR objectives.

50 48 Crucell s commitment to the world Taking responsibility on developing sustainability practices. From our supply base, we have selected those suppliers that seem most willing and able to work with us on improvements that will deliver real benefit. The innovative concept for the workshop includes inspiring speakers, organic catering, and full CO 2 compensation for the event, including associated travel. As our ideas about responsible supply chain management have evolved during 2010, we have decided to refine our initial target (set in 2009) to achieve 100% supplier coverage and monitoring in Sending a Supplier Code of Conduct and questionnaire to each and every one of our thousands of suppliers is unlikely to lead to more than superficial communication, whereas we are aiming for real engagement and follow-up. Our revised target is to start rolling out the Suppliers Code of Conduct and the vendor assessment questionnaire to a sample of around 100 key suppliers in The feedback we receive should give us a good indication of the impact our CSR program can have. We will report on our findings in In order to conduct our business in a responsible way, we need to know more about the social and environmental impact of the companies in our supply chain. This will enable us to make the best choices and support our suppliers who may need help to develop their own sustainability practices. An online tool for gathering information about our vendors practices and aspirations with respect to CSR was developed in 2010 and will be implemented in In March 2011, Crucell held the first of a series of CSR workshops for core groups of Crucell suppliers in three regions: Korea, Switzerland and the Netherlands. These are the three major locations in terms of Crucell s manufacturing and procurement volumes. Our aim is to bring the groups together annually to explore green ideas and work together There is an interesting story behind the substantial results delivered in Students from Hogeschool Rotterdam, a Dutch tertiary college, were invited to work with the Global Procurement department on development of the Suppliers Code of Conduct, vendor assessment tool and Supplier Day program. This arrangement was mutually beneficial, giving the students valuable experience in a corporate environment while enabling Crucell to make faster progress towards our goal of responsible supply chain management. Training our people Having made great strides in 2010, we are well on track to train all relevant Crucell employees in best practices for responsible supply chain management in 2011, as targeted. In preparation for this next step, the people in our Procurement organization were given an update on Crucell s CSR ambitions at a global event held in

51 Crucell s commitment to the world Taking responsibility 49 Responsible choices Our successful cool-box recycling program in Sweden is an example of how smart supply chain management can combine environmental and financial benefits. This local initiative encourages vaccine customers to return the cool boxes in which they receive the products. Normally, these temperature-controlled boxes are thrown away after a single use. Crucell pays for the return transport, which costs about 50% of the new box price, and reuses each container up to four times before disposing of it responsibly. The average monthly return rate in 2010 was 89% a great response and much higher than the 60% expected when the program was launched in Our Swedish organization sent out around 30,000 boxes of vaccines last year and purchased only around 6,700 replacements, so the program substantially cuts down on both waste and expenses. CSR information management The better we understand the impact our organization has, the better choices we can make as a business that is committed to delivering sustainable profit, measured in human and financial terms. Comprehensive and reliable information about our global activities and effects is essential in order to run Crucell with a warm heart and a cool head and communicate transparently with our stakeholders. Therefore, improving CSR information management was identified in 2009 as one of our top-five priorities for the coming years. The main targets set for 2010 were to roll out the Reporting Manual an information tool custom-built to fit Crucell s organization and CSR policy and achieve 100% company coverage regarding data collection. We have reached this goal for nearly all indicators, thanks to a tremendous effort from Crucell people at all levels and parts of our organization. The senior managers who shouldered responsibility for each of the 4P policy areas (P-owners) at the global level have shown real ownership and leadership. They, in turn, have received great support from a growing band of enthusiastic CSR supporters from the local affiliates. The active involvement of the Chief Operating Officer in Crucell s CSR Working Group sessions (held four times in 2010) has been invaluable for ensuring the alignment of this program with the Management Board s vision and strategy for Crucell. The better we understand the impact our organization has, the better choices we can make as a business that is committed to delivering sustainable profit, measured in human and financial terms. Rolling out a Reporting Manual may sound easy and effortless, but it was far from that. People grappled with the challenge of finding consistent definitions for key performance indicators (KPIs) and meaningful parameters for measuring outcomes. Training sessions and data collection had to be fitted into our employees already busy work days. However, by the end of 2010 a system for consistent and comprehensive reporting of information relevant to our CSR ambitions was in place, and company-wide data collection was on track. This establishes a 2010 baseline for our CSR performance, against which progress towards our ambitions can be evaluated over time. The insights we gain in the process will help us to refine and develop our CSR activities and ambitions. We see this as a continuous feedback loop enabling steady improvement.

52 50 Crucell s commitment to the world Taking responsibility Our fledgling system for CSR information management has its teething problems, of course. Looking at the 2010 data, we see some gaps and surprising differences across sites, which need to be investigated further. This uneven or uncertain quality of reporting mainly applies to specific quantitative KPIs in the categories of People and Planet. More intensive training may be required in these areas to ensure these KPIs mean the same thing to everyone contributing data. We are also thinking about the creation of incentive schemes to encourage and improve reporting. We will continue to develop, refine and improve our data collection methodology, scope and KPI set as we grow as an organization. As targeted, we will move on to formulating quantitative ambitions for environment, health and safety (EHS) parameters in Transparency A commitment to transparent communication with all stakeholders is fundamental to Crucell s CSR policy. We measure our performance in this regard against external benchmarks and our own targets for CSR development. In line with our ambitions, Crucell continued to show good performance and progress on major external benchmarks of transparency and sustainability in We are especially proud that Crucell was relisted on the Dow Jones Sustainability Index (DJSI) on September 9, 2010, for the second successive year. This significant achievement is in line with our target, expressed in 2009, to remain in the DJSI family of indexes the leading benchmarks for sustainable investment. The Dow Jones Sustainability Indexes were introduced in 1999 to indicate international corporations that have made sustainability an integral part of their business strategy. Companies are included on the basis of best-in-class performance. To find out more about the DJSI, go to Crucell participated in the Carbon Disclosure Project (CDP) in 2010, as in the previous year. This project is a worldwide, investor-driven initiative encouraging multinational corporations to report on their environmental impact, specifically in relation to carbon emissions and climate change. Our participation reflects our ambition to measure and manage Crucell s carbon footprint. For more information about the CDP, go to In the Netherlands, where Crucell has its global headquarters, Crucell is listed on the Transparantiebenchmark (Transparency Benchmark), an index published by the Dutch Ministry of Economic Affairs, Innovation and Agriculture. The Transparency Benchmark criteria were changed considerably in 2010 compared with the previous years, the index was expanded to include the country s 500 largest companies and the rating scale was increased from 100 to 200 points. The Ministry expected the new criteria to have a negative impact on scores. Nevertheless, Crucell showed good progress on the benchmark in 2010, scoring 96 out of 200 points compared with 38 out of 100 points in This substantial growth continues the trend seen since Crucell continues to make progress towards the goal of reporting on our CSR activities in accordance with Global Reporting Initiative (GRI) criteria and verified by external audit. The improvements in CSR information management implemented in 2010 take us a step further in this direction.

53 Crucell s commitment to the world Taking responsibility 51 People Crucell is committed to conducting business with integrity, in a way that respects the rights and needs of our large network of stakeholders, inside and outside the company. As a company dedicated to bringing innovation to global health, we recognize the importance of creating a working environment that attracts and retains talented people and fosters their ongoing development. In this section we describe what Crucell is doing to live up to its responsibilities towards people, focusing on three main themes: being a responsible employer, health and safety, and good business conduct. Crucell s VP Global Human Resources has taken on ownership of the People category within the CSR policy framework. He has driven Crucell s efforts to improve CSR performance and reporting in the area of people and organization during In consultation with the Management Board, the CSR Working Group has refined and expanded the initial set of key performance indicators (KPIs) for the People category (see table 3) and formulated qualitative targets corresponding to these indicators. Thanks to efforts from Crucell employees worldwide, the ambition to collect relevant People KPI data from all parts of the organization was achieved in 2010, giving us a better overview of our global organization and a baseline to evaluate further progress. Being a responsible employer Crucell can only fulfill its mission through the concerted efforts of the people making up our global organization. With their creativity, passion and drive, Crucell employees make a difference that matters especially to the millions of individuals who lead healthy and productive lives because of the innovative products we deliver. Taking the best possible care of Crucell s employees is therefore a responsibility with wide implications, and one we embrace. In line with Crucell s growing ambitions, recruitment was a high priority over the past year. We are determined to accelerate our pipeline programs in order to bring new products to market faster, thereby increasing our impact on global health. The total workforce expanded to in 2010, representing a 12% increase from Most of the new employees are based in the Netherlands and Switzerland, where Crucell s research and development (R&D) activities are located. Crucell remains an organization of relatively young people, with the average employee age being Excluding insourced staff in China.

54 52 Crucell s commitment to the world Taking responsibility Table 3: People KPIs and targets going forward KPI Quantitative/Qualitative Target Number of employees by gender Average age of employees Number of women in management Number of nationalities Total number of accidents Continue focus on equal-opportunity human resource management worldwide Report annually Fair and equitable representation Focus on cross-cultural teams 2011: LTC rate of 0.4 or less 2015: LTC rate below 0.2 Employee turnover % employees receiving regular performance reviews Voluntary turnover rate no more than 10% of workforce, excluding temporary staff > 95% Number of own recruits 1 Report annually Absenteeism 1 Set criteria in 2011 Report annually 1 New KPI added in Quantitative Qualitative Of the people who joined Crucell in 2010, 250 were recruited through referral and the strong employer s reputation on the labor market. We actively encourage our employees to talk to their contacts about job opportunities at Crucell or recommend suitable candidates. As talent attracts talent, this has proven to be an efficient and effective means to develop Crucell s capabilities in specialist areas. We also see it as an indicator of employee satisfaction, the key prerequisite for achieving our ambition to become an employer of choice. For this reason, the number of own recruits has been added to the list of People KPIs and will be reported annually. Crucell aims to maximize the number of own recruits. Another new KPI is absenteeism: the percentage of days missed from work (apart from planned leave). Our first experience with collecting these data in 2010 has pointed to the need to sharpen definitions, which we will do in We are interested in this parameter as a global measure of our employees health, well-being and job satisfaction. Voluntary employee turnover in 2010 was 12.93%. We aim to work proactively to minimize the number of people who choose to leave the company, with a target of less than 10% voluntary turnover. To achieve this, Crucell will continue to focus on creating the sort of working environment that not only inspires and empowers our employees, but also provides ample opportunities for learning and development within the organization.

55 Crucell s commitment to the world Taking responsibility 53 Developing talent Crucell is investing heavily in the skills and competencies of its people. Our Global Human Resources (HR) team has developed a long-term strategy for people development and identified this as a key CSR priority for taking Crucell where it wants to go. Implementation of this strategy started in 2010 and great strides have been made. A Global Manager Learning & Development was appointed in May, reflecting the importance we attach to building a continuous learning culture at Crucell. In collaboration with other key stakeholders, the Global HR team has launched two global training programs for Crucell managers at various levels. One program focuses on developing people s project management skills, the other on helping managers to develop financial and business acumen. Crucell employees have asked for this kind of support and this dovetails with the company s strategic goals. With a view to providing a gateway to learning and development opportunities for all Crucell employees, the Global HR department launched an online People Development Portal in July The basic launch version will be progressively enriched and expanded over the coming years. The idea is to offer our people a toolkit that will help them to reflect on their learning potential and seize opportunities for development. Crucell ran a leadership training for managers in Switzerland and the Netherlands in 2010, as part of an ongoing program established in We see a vital role in our organization for good leaders who can inspire and empower their teams of people to excel. An essential aspect of this leadership role is conducting regular performance reviews, which when done well provide people with feedback that will enable them to achieve their full potential. In 2010, about 95% of Crucell employees received regular performance reviews. Our aim is to ensure all employees receive regular performance reviews, and to increase their added value for both the employee and the company. Diversity and equal opportunity Crucell sees the value of diversity and strives to foster this through our recruitment practices and organizational structure, for example by building cross-functional and cross-site teams. Our site in the Netherlands employs people of 24 nationalities, closely followed by Switzerland with 23. This rich cultural mix fosters the cross-fertilization of ideas, as well as fun. Looking at the numbers of male and female employees in 2010, we see that Crucell has a reasonably balanced workforce in terms of gender (more than 47% females in 2010, compared with 45% in 2009). There was a substantially greater year-on-year increase (20% versus 10%) in the number of women compared with men. In our 2009 report, we noted the relatively low number of women in senior management positions as a point for attention. It is encouraging to see that the number of female employees with senior management roles increased by 45% in 2010 compared with 2009, bringing the total number to 84. Crucell is an equal-opportunity employer. We are committed to recruiting and promoting employees on the basis of talent and ability, without negative or positive discrimination on the basis of gender, race or age.

56 54 Crucell s commitment to the world Taking responsibility We value both gender and ethnic diversity and accordingly act as an equal opportunity employer. The characteristics of our workforce are as follows: China Italy Korea Netherlands Spain Sweden Switzerland UK USA Total 2010 Number of male employees Number of female employees Total number of employees ,398 Average age of employees Number of women in management Number of nationalities per location n/a 2009 Number of male employees Number of female employees Total number of employees ,248 Average age of employees Number of women in management Number of nationalities per location n/a 2008 Number of male employees n/a Number of female employees n/a Total number of employees n/a ,126 Average age of employees n/a Number of women in management n/a 3 58 Number of nationalities per location n/a 5 n/a 1 Not applicable, as Crucell s UK organization was launched in October

57 Crucell s commitment to the world Taking responsibility 55 Male/female ratio of Crucell employees in % 47% Male Female Number of nationalities per Crucell office in 2010 Health and safety Crucell invests in protecting the health, safety and well being of our employees. This is both a moral obligation and essential for building a strong and sustainable business. China 1 Italy 1 Korea 4 Netherlands 24 Spain 2 Sweden 1 Switzerland 23 UK 3 USA 7 For several years, Crucell has been working systematically to enhance workplace safety, focusing especially on accident prevention and preparedness. To ensure a coordinated approach, we have created the position of Global Head of Environment Health & Safety (EHS) and introduced a global EHS policy based on international standards and certification requirements. Safety officers have been appointed at our sites worldwide and sent to DuPont safety training, the gold standard in the chemicals and biopharmaceuticals industry. They take responsibility at the local level for introducing best practices and monitoring workplace safety.

58 56 Crucell s commitment to the world Taking responsibility Safety improvement: a case study In January 2011, a Crucell technician had a serious accident while handling glassware in one of our production facilities. The worker was pushing a tray of bottles sprayed with antiseptic under the laminar flow hood (air-control barrier) of a sterile handling unit. The bottles toppled and fell, and the technician suffered a deep cut as he tried and failed to catch them in his gloved hands. His colleagues had received safety training and responded appropriately, most probably saving his life. If we examine the risk factors in this situation the wet and slippery glassware, the laminar hood, the sterile gloves, the tray and handling method we see that they are all related to Good Manufacturing Practice (GMP) in our industry. Biopharmaceutical production must be conducted under highly sterile and controlled conditions in order to ensure the safety of the people who receive our products. However, this can potentially create unsafe conditions for production workers. The challenge we face is to safeguard both our employees and products. Our safety and process experts meet this sort of challenge by analyzing the precise circumstances in which accidents occur and looking for GMP compliant technical workarounds, or ways to avoid unsafe process steps altogether. At the same time, they focus on raising employees awareness of workplace risks and how to respond if an accident does occur. One of the tasks of safety officers is to collect data on accidents, with the aim of gaining a better understanding of risk factors and how to manage them. In our 2009 CSR report, we published accident data collected independently at our five manufacturing and/or development sites (covering 90% of the workforce) but noted the limitations of these data. For example, countries used different definitions and ways of measuring accidents. In 2010, we focused on taking EHS information management to the next level by introducing a global reporting system based on harmonized criteria. Access to more detailed information, collected from our production and R&D facilities using the same definitions, will give us greater power to continuously improve safety, using a plan-do-check-act approach. We are well on track towards this goal. A clear procedure for accident reporting, analysis and follow-up with corrective action has been introduced. An EHS Reporting Manual has been developed, local safety officers have been trained in its use and full-year data based on consistent criteria have been collected and analyzed. A reporting infrastructure has been established and is working well: local data are reported to the global EHS manager, who gives regular updates to the Chief Operating Officer (safety data on a monthly basis, other information quarterly). Accident reporting Agreeing on a consistent definition of reportable accidents was a challenge. After considerable debate, we have decided to adopt the United States Occupational Safety and Health Administration (OSHA) definition of lost time case rate (LTC) 1, excluding accidents that occur on the way to or from work and excluding medical conditions (such as fainting at work). Using consistent definitions allow trends to be followed. Analysis of the LTC among Crucell employees at our five main sites over the period (see graph) suggests that accident frequency has 1 The OSHA defines the LTC as the number of accidents resulting in at least one whole shift absence, per hours worked by 100 employees in 12 months (200,000 hours).

59 Crucell s commitment to the world Taking responsibility 57 been dropping. Whole-year LTC values decreased from 0.75 in 2009 to 0.40 in The target we have set for this KPI is to maintain or improve an LTC of 0.40 in 2011, which is the industry average. By 2015 we want to achieve a rate below 0.2. Increasing safety awareness Crucell s approach to improving workplace safety starts with accident preparedness: anticipating accidents that could occur and making sure that people know what action to take if they do. The importance of this is highlighted by a serious accident that occurred recently in one of our production facilities (see box left). Accident frequency (in LTC values) Other initiatives Crucell promotes the health and well-being of employees in other ways. Here are just a few examples of recent developments: y In Switzerland, improvements to the production line for Vivotif, Crucell s vaccine against typhoid fever, have made work more comfortable and pleasant for our people, as well as more efficient. y Our Spanish site has significantly improved security in order to increase the protection of our people and our products. y Free vaccination against seasonal influenza is offered to employees and their families each year, in countries where this is feasible and appropriate. In Korea, employees identified as being at risk of hepatitis A were also offered free vaccination with Crucell s Epaxal vaccine in 2010, while Crucell s travel vaccines were made available to employees and their families in the Netherlands and Switzerland. Our new reporting system provides a tool for understanding why accidents happen, so that we can take corrective action and prevent further occurrences. Ideally, we want to identify unsafe situations before any accident occurs. Reports of near misses (narrowly avoided accidents) are perhaps the most valuable information for managing risks and preventing accidents. Our accident data are classified into four groups according to the severity of their outcomes: near miss, first aid, medical treatment and fatality. On the basis of the assumed frequency of events in each category, we could expect to receive far more reports of near misses than serious accidents. Our data show the opposite pattern, suggesting that a relatively small proportion of near misses are being reported. Good business conduct Crucell adheres to high standards of ethics and transparency in dealing with all stakeholders. We take our legal and ethical obligations very seriously. Crucell s Code of Conduct guides employees in the high standards of behavior expected of them and their obligation to act with integrity at all times. The Code of Conduct urges employees to report any behavior or action that may be in breach of this code. A procedure for reporting non-compliance is in place and compliance offers have been appointed worldwide. We encourage every employee to report unsafe situations and near misses. With a view to raising the general level of safety awareness in the organization, we will hold a series of safety workshops for managers in They will be asked to act as role models and adopt a number of best practices in order to foster a culture of sustainable safety awareness.

60 58 Crucell s commitment to the world Taking responsibility Planet As a company dedicated to fostering the health and well-being of people worldwide, Crucell is very conscious of its responsibility to care for the planet our shared home. We are actively working to integrate environmental awareness into our strategic decision making and routine work practices so that we can live up to this responsibility. Our aim is to maximize our productivity and thereby our health impact while minimizing our environmental footprint. In 2009, we defined an initial set of KPIs for measuring our progress towards this goal. We also set targets for reducing energy and water consumption, minimizing our carbon footprint and improving waste management, basing these targets on the data then available in the organization. At the same time, we pointed out the need for more comprehensive and reliable data. With the development and implementation of the CSR Reporting Manual in 2010, we now have what we aimed for: company-wide data on relevant Planet KPIs, collected for the full calendar year using consistent criteria. This gives us a solid baseline for future reporting and target setting. Reporting methodology As targeted, the findings reported here are based on 100% data coverage for our global organization in We took a pragmatic approach to achieving this target, focusing primarily on collecting data from our five manufacturing and/or development sites, which together employ over 90% of the total workforce and account for almost all of Crucell s environmental impact. Solid data were also obtained from a representative marketing and sales office and extrapolated to cover the remaining offices in order to calculate our carbon footprint. Table 4: Planet KPIs and targets going forward KPI Quantitative/Qualitative Target Total water use Waste water Relative reduction 1 of 10% from 2010 baseline by 2020 Monitor and minimize Total energy use See CO 2 footprint CO 2 footprint Relative reduction 1 of 15% from 2010 baseline by 2020 Number, sort and impact of accidents 2011: LTC rate of 0.4 or less 2015: LTC rate below 0.2 Amount and characteristics of waste and disposal method Develop and/or refine waste minimization programs on all sites 1 Relative to workforce size expressed in full-time equivalents (FTEs). Quantitative Qualitative

61 Crucell s commitment to the world Taking responsibility 59 Total energy consumption (in kwh, million) Total water consumption (in m 3 ) 201, , , , Energy savings and safety: a dilemma A dilemma we face in our industry is that what makes sense from an environmental point of view can conflict with our responsibility to provide safe biopharmaceutical products. It seems logical to save energy by shutting down the air conditioning in our production facilities overnight or at the weekend. However, maintaining a constant and clean environment is essential for safeguarding against microbial contamination and ensuring the quality of the product. The energy gain from a temporary shutdown is outweighed by the energy that would be required to restore the correct environment and the time-consuming quality assurance tests that would be needed. Crucell s marketing and sales offices were found to account for less than 1% of total CO 2 emissions, confirming the validity of the method used for data collection and the importance of focusing our Planet efforts on the five production related sites. To safeguard the reliability of data, the managers responsible for data delivery have been trained in KPI definitions and CSR reporting rules. For example, they are instructed to report quantities and units as invoiced, without conversion. Any estimates must be indicated as such, and assumptions or algorithms must be documented. Pilot studies were conducted during 2010 to evaluate the quality of the data being collected, identify any problem areas and adapt the reporting methodology as needed. For example, the initial waste classification system was simplified in the course of the year to promote the consistency and value of reporting. We will report amounts of waste in three major categories: solid waste, special waste and recycled quantities. Waste water has been added to our KPI set. The EHS Reporting Manual has been developed progressively over the year and will continue to evolve as we learn by doing. We extend our thanks to all who have put so much time, energy and enthusiasm into this project. What they have produced, under the leadership of our global EHS director, is an indispensable tool for understanding and progressively improving Crucell s relationship with the planet. Energy consumption Crucell s global organization consumed a total of 88.4 million kilowatt hours (kwh) of energy in This represents a 44.6% increase compared to the previous year (see graph). Energy use includes electricity, natural gas, oil, and other fuels such as gasoline and diesel, all of which are converted to kwh. Electricity (from the grid) is Crucell s primary source of energy. Crucell s total energy consumption in 2010 was equivalent to that of approximately 4,935 average households (consuming 17,906 kwh). Parallel operations in Korea account for most of the increase in total energy consumption in 2010 compared with Our new Korean manufacturing facility on the Incheon site became fully operational in validation mode in 2010, while commercial production continued at the facility on the Shingal site. The latter will be decommissioned once the Incheon facility receives regulatory approval. The Incheon vaccine plant has around twice the capacity of the Shingal facility and has been engineered for highly efficient production. Manufacturing larger volumes more efficiently translates into significant gains in eco-efficiency. That is exactly what Crucell strives for: greater output and health impact with lower energy use.

62 60 Crucell s commitment to the world Taking responsibility Water management Crucell has decided to measure both total water consumption and waste water. Total water consumption in 2010 was 312,259 cubic meters, which was 41.1% higher than in Water is sourced from the grid, except for Madrid, Spain, where we operate a well on our premises. In 2010 Crucell generated 156,643 cubic meters of waste water. The addition of this new parameter to our KPI set reflects the high potential we see to decrease overall water consumption by optimizing water management in our production facilities. Higher occupancy at our sites in Switzerland and the Netherlands also played a role in the greater energy consumption. In Switzerland, total energy consumption increased by around a third in 2010 versus This reflects the fact that two formerly decommissioned buildings were brought on line again in the summer to house groups working on product process development and activities related to taking our Epaxal vaccine to the USA. Expansion of these groups is part of Crucell s strategy for accelerating pipeline growth. This also explains rising energy use in the Netherlands, where we significantly increased our R&D capabilities and activities in An additional building was rented to accommodate the rapidly growing workforce and provide space for new laboratories. The large increase in total water consumption during 2010 can be explained by the significant expansion of manufacturing and development operations, as discussed in the section on energy consumption. The observation that water consumption increased to a lesser extent than energy consumption might therefore reflect the success of recent efforts to improve water management, for example at facilities in Switzerland and Spain. At one of our production facilities in Switzerland, fresh water intake for plant steam generation has been cut substantially by optimizing the working of the steam and condensate system. The maximal amount of recoverable water is now being returned to the boiler. Besides saving water, this saves energy (as the recovered water requires less heating) and cuts down on water conditioning chemicals. Crucell s production plant in Madrid installed a new system for purified water production in The old system supplied 50% purified water and 50% concentrate (water with impurities), which was used to water plants on the site. The output from the new system is 85% purified water, decreasing waste to 15%. Improving water use is one of the top-five ambitions relating to CSR that we identified in We are targeting a 10% relative reduction in water use by ,2 Relative to workforce size expressed in full-time equivalents (FTEs).

63 Crucell s commitment to the world Taking responsibility 61 Waste Outcomes of our waste generation analysis for the global organization in 2010 are as follows: y Solid waste: 754,420 kilograms. y Special waste: 52,995 kilograms (representing 7% of total waste). y Recycled waste: 203,596 kilograms (representing 27% of total waste). Now that we have a good overview of the amounts and types of waste generated in our global organization, as well as the disposal method, we can start to develop and implement waste minimization programs. A workshop with EHS managers was held in March 2011 to spark ideas. Packaging Crucell continuously explores options for improving packaging, especially in ways that benefit both the environment and our customers. One of the success stories is our project to deliver Crucell s Quinvaxem pentavalent vaccine in smaller vials, which means less raw material, less weight to be transported and more efficient use of cold chain storage (for more details see the section on responsible supply chain management). In 2010 our regulatory team set out to reduce the size of the boxes carrying two vials of Dukoral cholera vaccine, which are considerably oversized. Smaller volumes would facilitate transport and cold storage, as well as saving packaging material. The team was disappointed to hear from the Canadian regulatory authorities that they could not carry out their plan. The information printed on the boxes must be in both English and French, and of a specified font size. These regulatory requirements designed to promote safe use of the product could not be met using a smaller box. This dilemma is an example of the complexity of factors that must be taken into consideration in the highly regulated vaccines industry. Carbon footprint Crucell s carbon footprint in 2010 was just over 21,000 tonnes CO 2 (21, tonnes). The carbon footprint was calculated using the Greenhouse Gas Protocol and accompanying conversion factors (to account for different energy mixes) per country. The most recent conversion factors were sourced from the UK Department for Environment, Food and Rural Affairs (DEFRA). Reducing our carbon footprint is one of the top-five CSR ambitions formulated in We are targeting a 15% relative reduction 2 from the baseline set in Planting the seed For years, Crucell s organization in Spain has taken a creative approach to recycling plastic packaging material that would otherwise go to waste. The large plastic containers in which syringes are delivered to Crucell are ideal for re-use as seedling trays. Crucell Spain sells the boxes to a nursery for this purpose. Though this is a relatively small-scale activity, it is a good example of the kind of CSR thinking Crucell wants to promote. A large volume of plastic is recycled in this way every year. Crucell Sweden shows the same spirit with its vaccine cool-box recycling program. Crucell continuously explores options for improving packaging, especially in ways that benefit both the environment and our customers.

64 62 Crucell s commitment to the world Taking responsibility Philanthropy Besides doing the very best we can to discover, develop, manufacture and market innovative products that protect people s health and well-being, we look for extra ways to make a positive difference to the lives of people worldwide. For reporting purposes, we group these noncommercial efforts under the heading of Philanthropy. This is a broad category that embraces everything from community outreach projects and efforts to improve healthcare access to the sharing of scientific knowledge and participation in sector sustainability initiatives. Community outreach Footprint Crucell encourages and facilitates employees involvement in philanthropic projects, in the belief that this benefits those who give help as well as those who receive it. This is the philosophy behind our global CSR outreach program Footprint, which gives Crucell employees an opportunity to visit disadvantaged communities where Crucell is working in partnership with local organizations to make a major difference to people s lives. In last year s report we introduced two of these partners: the South African Tuberculosis Vaccine Initiative (SATVI) and the nongovernmental organization (NGO) Friendship. SATVI conducts clinical trials of the tuberculosis vaccine Crucell is developing in collaboration with the Aeras Global TB Vaccine Foundation. Friendship is doing wonderful work with Crucell s support to extend the reach of the government s routine vaccination program in the remote northern districts of Bangladesh. Many children in this poor and inaccessible part of the country have been missing out on vaccinations prescribed by the national Expanded Program on Immunization (EPI). In the course of 2010, we enlarged the scope of these CSR outreach efforts to include support for the Max Foundation, a nonprofit organization that carries out small-scale projects to provide clean drinking water to communities in the southern part of Bangladesh. Crucell has so far sent three teams of Crucell volunteers to take part in these local projects and see for themselves the challenges faced by people living in the world s poorest and most needy communities. The employees have returned to work with a new understanding of the devastating effect infectious diseases have on communities without

65 Crucell s commitment to the world Taking responsibility 63 adequate access to childhood vaccines and clean water, as well as the importance of what they are doing in their daily work as Crucell employees to give the people in these communities a future. A blog entry posted on our Global Intranet by the Footprint team during the latest field trip says it all: We took the ambulance boat along the chars to an EPI session set up by Friendship in collaboration with local governmental agents. When we arrived there was a long queue of mothers with very young babies in their arms. And there we saw it, the babies were getting Quinvaxem! With funding from Crucell, Friendship has set up a cold chain to enable children in these remote char areas to be immunized. Even though all these tiny babies had to cry when they were injected, we were thrilled to know that it would significantly increase their chances of growing up into healthy teenagers. I went into this experience really not having a clue what to expect and it was amazing! The cliché term of a once in a lifetime opportunity is really the only way I can describe my experience in Bangladesh. Table 5: Philanthropy KPIs and targets going forward KPI Quantitative/Qualitative Target Number of doses donated Report annually Global policy for disaster relief (donations) Support of sector sustainability initiatives Participation in DJSI 1, CDP 2 and Transparency Benchmark to end due to delisting Continue participation in GRI 3 NGO partnerships New Footprint field trips scheduled for 2011 Further strengthen current NGO partnerships Explore potential new partnerships 1 DJSI Dow Jones Sustainability Indexes. 2 CDP Carbon Disclosure Project. 3 GRI Global Reporting Initiative. Quantitative Qualitative

66 64 Crucell s commitment to the world Taking responsibility Whenever possible, the Footprint volunteers have provided practical help during these field trips, for example by painting the children s ward of a hospital in South Africa or helping to dig a well in Bangladesh. They arrived with suitcases laden with small gifts from coloring sets, jewelry, sweets and toys to large boxes of disinfectant solutions and plasters which were received like treasures by excited children and parents. What the volunteers took away with them was equally treasured. One field trip member points out: I went into this experience really not having a clue what to expect and it was amazing! The cliché term of a once in a lifetime opportunity is really the only way I can describe my experience in Bangladesh. All Crucell employees can apply to take part in the Footprint field trips, and teams are carefully chosen to include people with different job functions and from different countries. They share their experiences with their colleagues on their return, thereby creating a ripple-on effect that is helping to raise the overall level of CSR awareness and enthusiasm in our organization. Community outreach in Korea In 2010, our Korean colleagues continued their efforts to make life a bit brighter for children taking part in the Dream Start program, a government health and welfare program targeting children from low-income families. Many of these children live in urban squats and lack access to even basic amenities like hot water, which means they are often teased and rejected at school. In 2009, Crucell volunteers were inspired to organize a bath day, combining a trip to the public baths with games, presents and a barbeque. This successful formula was repeated again in February 2010, providing a day of warmth and fun in the middle of winter. Around 20 Crucell employees and 25 Dream Start children participated. In the heat and humidity of July 2010, Crucell volunteers took the Dream Start collaboration a step further by organizing a clean-up day for two families living in Seongnam-si, one of the poorest neighborhoods in the city. The teams put up fresh wallpaper, renovated the floors and cleaned both houses. It was a great joy to see the kids playing around in a clean and tidy home, was how one volunteer summed up the day. What my colleagues did might seem like a small contribution to improving the lives of people in this squalid area, but it is a great start and I am very proud of all of them, said Sang Jeom Ahn, General Manager of Crucell Korea. This example highlights the importance of local as well as global CSR initiatives.

67 Crucell s commitment to the world Taking responsibility 65 Runa Khan, Executive Director Friendship Let me tell you a true story On char Bhatiborial under Sundarganj, Gaibandha, a young girl is already a mother at the age of 16. Khadija Begum was 15 when she married Shomizuddin. She had never received medical treatment or visited a doctor and had not received her tetanus injection (TT). She was not even aware that adolescent girls should receive three doses of TT under the Government Expanded Program on Immunization (EPI) to minimize the risk of infection during delivery. To her knowledge, the government has never held an EPI session at Bhatiborial and she does not recall a health worker ever visiting the char for health education. The closest family welfare center was approximately 3 hours away. To get there, she would have to walk 2 kilometers over sand, wait for a boat that may come only twice a week (and not even at a fixed time), and then take a van ride, making her journey both tiring and costly. In May 2010, when she was about 4 months pregnant, a team showed up on her island not only to conduct an EPI session on the char itself but also to inform and educate the community through household visits and group meetings. Khadija s son, Mohammad Khairul, is now 5 months old and under the Friendship Crucell EPI Support Program has received his BCG (tuberculosis), Quinvaxem 1 and 2 (pertussis, diphtheria, hepatitis B, tetanus and Haemophilus influenzae type B), and OPV 1 and 2 (polio) vaccine doses. More importantly, Khadija is aware of when his next dose is due and will be bringing him to the center for it. If by chance she forgets, she is secure in the knowledge that a Friendship health worker will come by to remind her. Khadija Begum s story is one of thousands. This outcome is made possible by the joint efforts of Crucell and Friendship. NGO partnerships Crucell and Friendship Crucell s partnership with Friendship is a good example of how we work with NGOs to overcome barriers to healthcare access in developing countries. Crucell provides funding and scientific expertise, as well as practical support, to enable organizations that understand the local needs, culture and healthcare challenges to develop targeted solutions. Friendship is a value-based national organization dedicated to improving the lives of people living in the remote riverbank and char areas of northern Bangladesh. The chars (nomad islands) are isolated from the mainland in terms of physical distance, access to healthcare, and other basic resources. Rates of morbidity and mortality due to vaccine-preventable diseases are high, especially among children. The partnership between Crucell and Friendship is successfully tackling this problem by facilitating the government EPI program, which aims to deliver the WHO recommended schedule of vaccines to all children under five. We focus on logistics and infrastructure, providing a riverbased health service system with floating hospitals, satellite clinics and community medics. The Friendship Crucell program has purchased three boats, recruited staff who help the government healthcare

68 66 Crucell s commitment to the world Taking responsibility workers to deliver the regular vaccine schedule and monitor delivery, trained community medics and leaders, and conducted community meetings to increase awareness about vaccine-preventable diseases and the importance of the EPI program. Crucell employees help locals dig a well in Bangladesh. Steven and Joke Le Poole, Directors of the Max Foundation Both Crucell and the Max Foundation want to reduce child mortality. We use our privileged position to fund projects that provide high health value per euro spent. We are especially impressed that Crucell has the vision to support our non pharmaceutical approach based on wells, latrines and hygiene training. We really value the cooperation with Crucell as far too many children still die from water-borne infectious diseases. Together we can make the difference. Crucell not only supports us but also recently visited the project in Bangladesh where they could see first-hand the major impact their program had on the local community. These efforts have greatly increased the rate of vaccination coverage in the target region. From May 2010, when the Friendship Crucell EPI Support Program was inaugurated, to the end of the year, all but 50 of the 704 planned EPI sessions were held; problems such as extreme rains account for the missed sessions. A total of 1809 babies received Quinvaxem doses at 6, 10 and 14 weeks of age, in accordance with the EPI schedule. This gives them protection against five common and potentially deadly childhood infections. The infants were also vaccinated against tuberculosis, polio and measles, and received vitamin A, which reduces child mortality and the risk of river blindness. Crucell and the Max Foundation Crucell is proud to be supporting the Max Foundation in its work to save children s lives through community-based water projects in Bangladesh. Since its foundation in 2004, over 200,000 people have been supplied with clean drinking water and sanitation. The 1,000th project was completed in March The foundation was set up by Dutch couple Steven and Joke Le Poole after their 8-month old son Max died from a rare viral infection. They wanted to turn their loss into something positive, says Crucell s Chief Strategy Officer Arthur Lahr, who brought the Max Foundation to the attention of his Management Committee colleagues. For Crucell, partnering this NGO is a logical choice: It is gratifying to be able to support a nonprofit organization that shares our drive to improve children s lives. Immunization and clean water are the most cost effective contributors to child health, says CEO Ronald Brus. Every euro donated to the foundation goes towards microsanitation projects.

69 Crucell s commitment to the world Taking responsibility 67 Bringing color to children s lives Crucell employees gave generously to good causes in Here are two examples we particularly like. y Child ambassadors for Stichting Kinderpostzegels (Foundation for Childrens Stamps) sold a record number of stamps and cards during a lunchtime visit to Crucell s Dutch site in October 2010, raising over 1,400 from employees. Crucell management doubled their contribution. y Employees in Switzerland donated money to purchase over 200 coloring sets for the children in Bangladesh. The initiative was sparked by a presentation on Friendship during a general staff meeting. Access to healthcare Crucell s work with Friendship is an example of a targeted community initiative to remove barriers to healthcare access. Crucell also works on this issue at the international and global level, through close and continuous engagement with a wide range of organizations. Here are the 2010 highlights. Crucell supported the International Pediatric Association (IPA) in its efforts to drive EPI development by empowering its members to take on an advocacy role. The IPA believes that pediatricians have a crucial role to play in advising their governments on the best vaccines and implementation strategies. Crucell gave the IPA an unrestricted grant to run an advocacy workshop during its latest international congress, held early August in Johannesburg, South Africa. Crucell also provided a follow-up grant to help in-country implementation of the best advocacy proposals. At the same conference, Crucell supported educational activities through the IPA. These focused on innovative strategies for simplifying vaccine delivery, which are seen to be key for reaching neglected populations. Crucell s collaboration with the nonprofit organization PATH to make Quinvaxem available in a Uniject device underlines our commitment to this type of innovation (see page 44). In November 2010, the launch of a global Coalition Against Typhoid (CaT) was announced by the Sabin Vaccine Institute in Washington, DC, which will serve as the secretariat. Crucell played a significant role in bringing together this worldwide collaboration of stakeholders in the field of typhoid fever. Despite the availability of low-cost vaccines against typhoid and a WHO Strategic Advisory Group of Experts recommendation for their use, typhoid fever vaccination has been a low priority for many countries, including those most impacted by the disease, said Dr Christopher Nelson, Director of the CaT secretariat.

70 68 Crucell s commitment to the world Taking responsibility Crucell also worked on healthcare access improvements as a member of: y the IFPMA Biologicals & Vaccines Committee, which contributes to discussions with the World Health Organization (WHO) on general vaccination policies; y the advisory group for Project Optimize, a WHO/PATH collaboration aimed at developing innovative delivery systems to ensure that vaccines get to the right place, at the right time, in the right condition; y the European Vaccine Manufacturers (EVM), part of the European Federation of Pharmaceutical Industries and Associations, which is committed to working in partnership with EU institutions to support vaccine policy development and promote vaccine innovation. Crucell was the vaccine industry representative (for the third successive year) on the formal advisory Program & Policy Committee of the GAVI Alliance, a public-private partnership with the mission to improve access to vaccines in the world s poorest countries. In 2010, the committee played an important role in the development of a new GAVI Alliance strategy and business plan for the period. Other key issues were how to prioritize new vaccine applications in order to bridge a funding gap, a strategy for resources mobilization, and health system strengthening. Crucell s innovative work with international organizations dedicated to immunization program development paved the way for our CEO Ronald Brus to be nominated by the vaccine industry in industrialized countries to represent the constituency on the Board of the GAVI Alliance. Vaccine donations In 2010, Crucell donated 321,000 doses of MoRu-Viraten vaccine against measles and rubella to Unicef to assist earthquake victims in Haiti. The vaccines were shipped in August The donation was made as part of the emergency aid campaign organized by the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA), of which Crucell is a member. Contributing to science Crucell contributes to the advancement of science and healthcare by sharing knowledge and expertise. In 2010, Crucell participated in 58 1 international conferences and many more seminars, informal meetings and media presentations. Our leading scientists gave over 25 1 public lectures and presentations to their peers on a wide range of topics, including innovative technologies for vaccine and antibody discovery, design and manufacturing; novel approaches to fighting major infectious diseases; and results emerging from Crucell s research and development programs. 1 Including PERCIVIA events.

71 Crucell s commitment to the world Taking responsibility 69 In 2010, Crucell once again sponsored events and symposia to facilitate information exchange among key opinion leaders and promote scientific development. One example is the Seventh Respiratory Syncytial Virus Symposium held in Rotterdam, the Netherlands, in December As well as sponsoring this meeting of leading RSV investigators, Crucell s Innovation and Discovery Laboratories presented two researchers with a Crucell Innovation Award in recognition of their outstanding work in this field. A total of 15 scientific papers by Crucell researchers were published in peer-reviewed journals in Sector sustainability initiatives In 2010, Crucell participated in a number of initiatives that provide an objective measure of corporate performance on sustainability issues, including the Dow Jones Sustainability Index (DJSI), the Carbon Disclosure Project (CDP) and the Transparantiebenchmark (Transparency Benchmark), an index published by the Dutch Ministry of Economic Affairs, Innovation and Agriculture. See page 50. Crucell remains committed to making sustainability issues an integral part of strategic decision-making, with the aim of maximizing our contribution to a better world. Conclusion Corporate social responsibility (CSR) is an integral part of Crucell s mission to conduct good business, for the good of humanity. Crucell is committed to continuous development of its approach to CSR reporting and the engagement of stakeholders in dialogue about sustainability issues. We are again pleased to have taken important steps in this direction during Crucell welcomes feedback on this report or any issues related to our CSR activities. Your opinion matters to us. Reactions can be sent to [email protected].

72 70 Crucell s commitment to the world Taking responsibility Appendix Performance overview What we said (2009 target setting) What we did (2010 actions) Where we are (2010 outcomes) Where we are going (2010 target setting) KPI: Prevention of illness and deaths Continuous improvement Report annually Maintained similar levels of prevention compared with 2009 Prevented more than 3.6 million cases of infectious disease and 809,823 deaths Continuous improvement Report annually Number of pipeline products Report annually Expanded and advanced our pipeline of investigational vaccines and antibodies Crucell has 12 candidate products in its R&D pipeline Report annually Animal welfare Continuous improvement 3Rs (Reduce, Refine, Replace) Continued to apply 3R principles to animal testing for preclinical R&D Essential safety studies are conducted to minimal extent required by law and in accordance with highest international standards Continuous improvement 3Rs R&D expenses Report annually Reported in press release (2010 financial results, February 7, 2011) and in this CSR report Annual R&D expenses 100 mln in 2010 versus 70.2 mln in 2009 Report annually CSR information management improvement In 2010 roll out Reporting Manual In 2010 report with 100% company coverage In 2011 set action plans (quantitative targets) Responsible supply chain In 2010 incorporate PSCI 1 principles into procurement policy In 2011 train all relevant employees In % supplier coverage & monitoring Transparency objectives GRI 2 A+ level CSR reporting in 2015 Remain in DJSI 3 In 2010 improve CSR web page Developed, finetuned and rolled out Reporting Manual Collected and analyzed company-wide data Produced Supplier Code of Conduct based on PSCI principles and incorporating Crucell-specific CSR ambitions and guidelines Created vendor assessment questionnaire to survey key suppliers Devised strategy and program for Crucell supplier days (CSR workshops) Made substantial further progress with CSR reporting and performance, as measured by a range of external benchmarks (DJSI, CDP 4, GRI and Dutch Transparency Benchmark 5 ) Improved CSR page on Crucell website A system for consistent and comprehensive reporting is in place Data coverage is 100% Areas where further training or reporting incentives are needed have been identified Strategy and tools are in place to engage key suppliers in constructive dialogue about Crucell s CSR guidelines and ambitions Self-declared GRI level C; DJSI listing for second successive year; Transparency Benchmark score 96/200 Web page outlines Crucell s CSR ambition and strategy, and provides links for more information/contact 2011: Set action plans and set quantitative targets for environment, health and safety (EHS) indicators In 2011: train all relevant employees in responsible supply chain management In 2011: 80% of top 100 vendors to sign Supplier Code of Conduct (CSR declaration) and take part in CSR assessment Beyond 2011: full coverage & monitoring of supplier target group Hold supplier day with focus on CSR in three countries in : Further improve CSR web page and continue to develop reporting practices 2015: GRI A rating 1 PSCI Pharmaceutical Supply Chain Initiative. 2 GRI Global Reporting Initiative. 3 DJSI Dow Jones Sustainability Indexes. 4 CDP Carbon Disclosure Project. 5 Transparantiebenchmark (Transparency Benchmark), an index published by the Dutch Ministry of Economic Affairs, Innovation and Agriculture. Quantitative Qualitative

73 Crucell s commitment to the world Taking responsibility Appendix 71 People overview What we said (2009 target setting) What we did (2010 actions) Where we are (2010 outcomes) Where we are going (2010 target setting) Number of employees by gender Formulate target in 2010 Achieved 100% data coverage and formulated target Total workforce 1,398 1 (12% increase from 2009); ~47% women Continue focus on equal-opportunity human resource management worldwide Average age of employees Report annually Achieved 100% data collection and formulated target Average age 40 years Report annually Number of women in management Formulate target in 2010 Achieved 100% data collection and formulated target 84 women in senior management positions, 45% increase versus 2009 Fair and equitable representation Number of nationalities Formulate target in 2010 Achieved 100% data collection and formulated target Teams show high cultural diversity, particularly in the Netherlands and Switzerland Focus on cross-cultural teams Total number of accidents Formulate target in 2010 Defined reporting criteria, achieved 100% data collection and formulated target Lost time case (LTC) rate 2 of : LTC rate of 0.4 or less 2015: LTC rate below 0.2 Employee turnover Formulate target in 2010 Achieved 100% data collection, refined KPI definition and formulated target Strong and successful recruitment drive Learning & development (L&D) identified by global Human Resources department as key CSR priority; global L&D manager appointed and multiple L&D initiatives launched Voluntary turnover in 2010 was 12.93% Voluntary turnover rate no more than 10% of workforce, excluding temporary staff Percentage of employees receiving regular performance reviews Formulate target in 2010 Achieved 100% data collection and formulated target ~95% > 95% Added two new KPIs to initial set: Number of own recruits* 250 new employees in 2010 were recruited by referral Report annually Absenteeism* Wide variation in data across sites, suggesting need to sharpen definition of this new KPI Set criteria in 2011 Report annually 1 Excluding 31 insourced staff in China. 2 US Occupational Safety and Health Administration (OSHA) definition. Quantitative Qualitative

74 72 Crucell s commitment to the world Taking responsibility Appendix Planet overview What we said (2009 target setting) What we did (2010 actions) Where we are (2010 outcomes) Where we are going (2010 target setting) Total water use Relative reduction 1 of 10% by 2020 In 2010 achieve 100% coverage (i.e. baseline) Achieved significant water savings by installing a new purified water generation plant in Spain and improving steam boiler operations in a Swiss facility Initiated full operational testing at new Korean facility in addition to commercial operations at old site and increased activity at two Swiss facilities, leading to overall increase in water consumption Achieved 100% data coverage. Waste water was monitored and reported as an additional parameter 312,259 m 3 (41.1% increase versus 2009 due to operational increases) 156,643 m 3 of waste water Relative reduction 1 of 10% from 2010 baseline by 2020 Monitor and minimize waste water Total energy use See CO 2 footprint In 2010 achieve 100% coverage Increased operations in Korea and Switzerland, leading to overall increase in energy consumption (see water use ) Total energy use: 88.4 million kwh (44.6% increase versus 2009 due to operational increases) See CO 2 footprint CO 2 footprint Relative reduction 1 of 15% by 2020 In 2010 set baseline In 2011 set action plans The carbon footprint was calculated using the Greenhouse Gas Protocol and latest conversion factors sourced from the UK Department for Environment, Food and Rural Affairs (DEFRA) 21, tonnes CO 2 Relative reduction 1 of 15% from 2010 baseline by 2020 Number, sort and impact of accidents Formulate target in 2010 Defined reporting criteria, achieved 100% data collection and formulated target Lost time case (LTC) rate 2 of : LTC rate of 0.4 or less 2015: LTC rate below 0.2 Amount and characteristics of waste and disposal method Implement waste minimization programs on all sites System for global data collection and analysis developed, piloted and refined; 2010 baseline established; recycling initiatives mapped Plan drawn up for workshop early 2011 to share best practices and develop waste minimization programs Solid waste: 754,420 kg Special waste: 52,995 kg (7% of total waste) Recycled waste: 203,596 kg (27% of total waste) Develop and/or refine waste minimization programs on all sites 1 Relative to workforce size expressed in full-time equivalents (FTEs). Quantitative Qualitative

75 Crucell s commitment to the world Taking responsibility Appendix 73 Philanthropy overview What we said (2009 target setting) What we did (2010 actions) Where we are (2010 outcomes) Where we are going (2010 target setting) Number of doses donated Report annually Donated 321,000 doses of MoRu-Viraten vaccine against measles and rubella to Unicef to assist earthquake victims in Haiti 321,000 donated doses of MoRu-Viraten vaccine were shipped in August 2010 Report annually Global policy for disaster relief (donations) Support of sector sustainability initiatives Further Crucell involvement Participated in a range of initiatives measuring sustainability and CSR transparency: DJSI 1, CDP 2, GRI 3 and Transparency Benchmark 4 Self-declared GRI level C; DJSI listing for second successive year Transparency Benchmark score 96/200 Participation in CDP Participation in DJSI, CDP and Transparency Benchmark to end due to delisting Continue participation in GRI NGO partnerships Liaise with key NGOs and evaluate partnership yearly Conducted two Footprint field trips to Bangladesh and planned a third trip which was held early in 2011 Strengthened and expanded partnerships with NGOs Evaluated partnerships Strong employee involvement in and support for community outreach activities Crucell Friendship partnership is highly successful in helping Bangladeshi government to improve immunization coverage in remote areas In partnership with the Max Foundation (new partner in 2010) Crucell is supporting microsanitation projects in Bangladesh New Footprint fieldtrips scheduled for 2011 Further strengthen current NGO partnerships Explore potential new partnerships 1 DJSI Dow Jones Sustainability indexes. 2 CDP Carbon Disclosure Project. 3 GRI Global Reporting Initiative. 4 Transparantiebenchmark (Transparency Benchmark), an index published by the Dutch Ministry of Economic Affairs, Innovation and Agriculture. Quantitative Qualitative

76 74 Crucell s commitment to the world Taking responsibility Field trips Impression photo s taken by Crucell employees during Footprint field trips, Crucell s CSR outreach program.

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