Public credibility is crucial to business activities. In the life science industry, high ethical standards are necessary because of the responsibility and impact of our work on patients. Daiichi Sankyo’s R&D Division defined “Ethics and Patient Safety First” (a statement that encapsulates our commitment to prioritizing ethics and patient safety above scientific and business interests) as our slogan to foster a “Patient-Centric Mindset”, and our research and development activities are based on this philosophy. We are deeply committed to the safety of people’s and patients’ health and lives and are dedicated to fostering values based on a high level of ethics. The following introduces our R&D activities and ethical response in those activities.

• Ethical Considerations in Research Using Human-derived Biological Materials and Information
• Ethical Considerations in Animal Experiments
• 3Rs of Animal Usage
• Handling of Biohazards and Genetically Modified Organisms
• Fair Utilization of Genetic Resources
• Ethics in Clinical Trials
• Collaboration with Contract Research Organizations
• Disclosure of Clinical Trials information

Ethical Considerations in Research Using Human-derived Biological Materials and Information

In order to deliver safer drugs with higher efficacy to patients quickly, Daiichi Sankyo Co., Ltd. evaluates drug candidates using human-derived biological materials, such as tissues, cells, blood, or genes, as well as information from human subjects. We conduct proactively cutting-edge, multi-omics (e.g., Genomics, Proteomics, Metabolomics) analysis using these materials for promoting biomarker research. These research activities aim to predict the effectiveness and side effects of drugs in clinical trials early and avoid unnecessary treatment for patients. In new research areas, specifically regenerative medicine and cell therapy, we use induced pluripotent stem (iPS) cells, somatic stem cells, or a combination of human-derived biological materials and genetic engineering technology to try developing new therapies.
Research using human-derived biological materials and information may have significant physical and mental effects on the research subjects or have great impact on the society and may raise various ethical, legal, or social issues. Therefore, we conduct various types of research using these materials and information in accordance with the regulations in each country.   In Japan, under   the　National guideline,   “Ethical Guidelines for Medical and Biological Research Involving Human Subjects,” Daiichi Sankyo has established internal regulations, namely the “Detailed Regulations for Ethical Research on Human Tissue, Information and Other Human Material Research.” In accordance with these regulations, we have also established the “Ethical Research Practice Committee for Research on Human Tissue, Information and Other Human Material”, which includes external specialists, and conduct research while objectively ascertaining its necessity and usefulness. We respect and protect the rights and dignity of research subjects and have thorough discussions on the ethical issues in conducting the research. When conducting the research, we obtain voluntary prior consent from research subjects and manage their personal information, including genetic information, in compliance with the revised “Act on the Protection of Personal Information.” We also disclose any research agenda on the Company’s   corporate website as necessary. In addition to annual in-house education, all personnel involved in the above research are required to undergo the Education for Research Ethics and Integrity program   provided by the Association for the Promotion of Research Integrity (APRIN) to ensure appropriate research implementation.

Ethical Considerations in Animal Experiments

Daiichi Sankyo Co., Ltd. has established an internal regulation called the “Detailed Regulations on Animal Experimentation,” which is based on Japanese laws and guidelines, including the “Act on Welfare and Management of Animals,” the “Standards for the Care and Keeping of Laboratory Animals and the Alleviation of Pain and Suffering  ,” and the “Basic Guidelines for the Conduct of Animal Experiments at the Conducting Institutions under the Jurisdiction of the Ministry of Health, Labor and Welfare.”  We promote the 3Rs of Animal Usage^*1 based on our understanding of the importance of the above.
Before conducting an animal experiment, we evaluate the target molecules and compounds using in silico and in vitro evaluation models, which are introduced in the next section (3Rs of Animal Usage) to narrow down compounds    to be evaluated in animal experiments. 
All animal-use protocol must be reviewed at the planning stage for scientific appropriateness, alternative methods, and experiment details, including the 3Rs of Animal Usage, by the Company’s Institutional Animal Care and Use Committee, and only the protocols that have been approved can be carried out. We also provide in-house annual training for animal experimentation personnel.
To confirm that our animal experiment facilities are in compliance with Japanese laws and guidelines, we conduct regular self-inspections and also seek accreditation from third-party certifying organizations. The R&D Division has continued to receive its full accreditation from the AAALAC International^*2. The Biologics Division (the Vaccine Research Laboratories) has continued to receive its certification from the Center for Accreditation of Laboratory Animal Care (the Japan Pharmaceutical Information Center).

• *1Replacement (methods that avoid using animals), Reduction (use of fewer animals), and Refinement (minimize or eliminate pain and distress). 
• *2Association for Assessment and Accreditation of Laboratory Animal Care International.

3Rs of Animal Usage

The Institutional Animal Care and Use Committee reviews animal-use protocol prior to enactment and, in addition to stringent evaluation, enforces the following regulations with regards to the 3Rs of Animal Usage.

1) Replacement
The availability or appropriateness of completely replacing the animal test with alternative test measures or replacing a portion of animal test subjects with animals that are ranked lower from a phylogenic perspective is investigated, and animal experiments are only conducted if there is no alternative found.

2) Reduction
The number of animals to be used is justified by determining the minimum number of subjects necessary to accomplish the experiment’s goals based on statistical method. Even if the specifications of the experiment call for spare animals or the exclusion of certain animals, the usage of additional animals will not be approved unless deemed scientifically necessary.

3) Refinement
Procedures may only be performed on animals if it is determined that the procedure in question will cause the minimum amount of pain and distress regardless of the experiment’s goals. In addition, all animal-use protocol applications must include considerations of humane end points^*3 in addition to experimental end points.

Specifically, we have adopted the in silico prediction of pharmacokinetics and toxicity by the computer simulation and the in vitro evaluation method using cultured cells from animals or humans prior to conducting an evaluation using animals.
In addition, with advances in micro blood sampling and analytical technology, we have significantly reduced the number of animals required in small rodent studies and reduced the number of animals used for pharmacokinetic evaluation of compounds by adopting a technique to individually analyze the multiple compounds administered.
We confirm the latest trends on the philosophy and ideas on the 3Rs of Animal Usage by attending academic and other meetings regarding animal experiments in Japan and overseas. Thereby, we conduct education based on updated information to ensure that our researchers always possess the level of ethics that society expects in animal usage. In addition, researchers undergo training from instructors certified by the Japanese Society for Laboratory Animal Resources on techniques to use in performing experimental procedures on animals.

*3Standards for suspending or canceling animal experiments established so as not to cause excessive pain or destress to laboratory animals.

Handling of Biohazards and Genetically Modified Organisms

Daiichi Sankyo Co., Ltd. introduced new modality tools, conduct research on regenerative medicine and cell therapy, and properly handle genetically modified organisms and biohazard materials related to the research. Specifically, Daiichi Sankyo has established the “Detailed Regulations for Biosafety”, an internal biosafety manual, in order to handle pathogens and pathogen-containing materials safely and in compliance with the laws and regulations concerning these biohazard materials, including the “Act on the Prevention of Infectious Diseases”^*4 and the “Act on Domestic Animal Infectious Diseases Control.” The Biosafety Committee determines the proper operating rules for handling biohazard materials. In addition, in order to properly handle genetically modified organisms in accordance with the Cartagena Act,^*5 we have established the “Detailed Regulations on Recombinant DNA Experiments”.”The Recombinant DNA Safety Committee confirms in advance that the experiment is planned in accordance with the Cartagena Act.
In addition to the annual in-house education, we require all personnel involved in such research to undergo the Education for Research Ethics and Integrity program provided by the Association for the Promotion of Research Integrity (APRIN) to prevent experimental accidents and violations of laws and regulations.

• *4 Act on the Prevention of Infectious Diseases and Medical Care for Patients with Infectious Diseases.
• *5Act on the Conservation and Sustainable Use of Biological Diversity through Regulations on the Use of Living Modified Organisms.

Fair Utilization of Genetic Resources

Concerning the preservation of biodiversity, sustainable use of components of biodiversity, and fair and equitable sharing of the benefits arising out of the utilization of genetic resources, we abide by the Convention on Biological Diversity.

Ethics in Clinical Trials

Daiichi Sankyo Co., Ltd. has established the Global Policy of Clinical Trials Standards and conducts clinical trials in accordance with global standards in consideration of the human rights and safety of participants in clinical trials and based on high ethical and scientific standards. Clinical trials are conducted in compliance with applicable regulations, the Declaration of Helsinki^*6, and ICH^*7-GCP^*8, upon obtaining individual’s voluntary consent after providing a detailed explanation (informed consent).
We conduct all clinical trials after both ethical propriety and scientific validity are confirmed in accordance with the internal review processes. Particularly, we ensure the first-in-human study is appropriate ethically and scientifically through clinical trial review meetings that include qualified physicians as review members. Furthermore, clinical trials are conducted after an external independent committee (Institutional Review Board / Independent Ethics Committee) reviews the ethics (human rights of trial participants, etc.) and scientific validity, and approves the conduct of clinical trials.
We ensure the training of the standard operation procedures aimed for the ICH-GCP and clinical trial ethics to people who are engaged in clinical trials.
An independent department of the Company conducts the audit of clinical trial activities and drives remedial actions and preventive measures.

• *6 Ethical principles for medical research involving human subjects.
• *7Abbreviation of “International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use”.
• *8 Abbreviation of “Good Clinical Practice”, an international ethical, scientific and practical standard to which all clinical research is conducted.

Collaboration with Contract Research Organizations

Disclosure of Clinical Trials information

Daiichi Sankyo Co., Ltd and applicable group companies register Daiichi Sankyo sponsored Phase 1 to Phase 4 clinical trials on public clinical trial registries, such as ClinicalTrials.gov, EU-CTR, EU-CTIS, JapicCTI, and jRCT, in line with applicable regulations and the guidelines and principles of industry groups.
Our clinical trial information is also accessible from our clinical trial information portal(www.daiichisankyo.com/rd/clinical_trials/).

In addition, we prepare clinical trial summaries in plain language for patients who participate in a Daiichi Sankyo sponsored clinical trial.
We also provide the opportunity for external researchers to access clinical trial data of products that obtained approval in Japan, Europe, and the U.S. under a defined process through Vivli clinical research data sharing platform(vivli.org).