Getting public credibility is crucial to our company’s business activities. In the life science-oriented industries, in particular, noble ethical standards are strongly required because of the responsibility and impact of our work on patients. In fiscal 2016, 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 or business interests) as its global R&D unit core value, and our research and development activities are based on this philosophy. We are aware that we are deeply committed to the safety of people`s and patients' health and lives, and we therefore are committed to fostering values based on higher 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
In order to deliver safer drugs with higher efficacy to patients more quickly, we evaluate drug candidates using human-derived biological materials, such as tissues, cells, blood, or genes, as well as information from human subjects. We are conducting 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.
On the other hand, research using human-derived biological materials and information may have significant physical and mental effects on the research human subjects or have great impact on the society and may cause various ethical, legal, or social issues. Therefore, in accordance with Japanese guidelines, including “the Ethical Guidelines for Medical and Health Research Involving Human Subjects” and “the Ethical Guidelines for Human Genome / Gene Analysis Research”, 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 detailed regulations, we have also established “the Ethical Research Practice Committee for Research on Human Tissue, Information and Other Human Material” with members that include external specialists, and conduct research while objectively ascertaining its necessity and usefulness. We respect and protect human rights and dignity of research human subjects and have thorough discussions on the ethical issues in conducting the research. When conducting the research, we obtain voluntary prior consent from research human 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. Researchers engaged in work using human-derived materials and information are required to receive research ethics training from the Association for the Promotion of Research Integrity (APRIN) as well as in-house education each year.
Ethical Considerations in Animal Experiments
Daiichi Sankyo has established internal regulations called “the Detailed Regulations on Animal Experimentation”, which is based on Japanese laws and guidelines, including “the Act on Welfare and Management of Animals and the fundamental guidelines” issued by the Ministry of Health, Labour and Welfare and related activities. Understanding the importance of these rules, we practice the 3Rs of animal usage.*1
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. In this way, we are working on the 3Rs of animal usage.
All animal-use protocol must be reviewed 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. Moreover, researchers conducting animal research are required to undergo specialized educations each year.
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 Kasai R&D Center has continued to receive its certification from the Japan Health Sciences Foundation’s Center for Accreditation of Laboratory Animal Care and Use. The Shinagawa R&D Center has continued to receive its full accreditation from the AAALAC*2 International.
- *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, on top of stringent evaluation, enforces the following regulations with regard to the 3Rs of animal usage.
The availability or appropriateness of completely replacing the animal test with alternative test measures or replacing a portion of animal tests 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.
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.
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.
As a specific effort for the 3Rs of animal usage, we have adopted the in silico prediction of pharmacokinetic properties on the computer and the toxicity evaluation method using cultured cells from animals or humans prior to conducting an evaluation using animals.
In addition, by acquiring the micro blood sampling and analytical technology, we have significantly reduced the number of animals required for pharmacokinetic evaluation in toxicity tests of rodents, 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 conducting 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 to laboratory animals.
Handling of Biohazards and Genetically Modified Organisms
We introduce new modality tools, conduct research on regenerative medicine and cell therapy, and handle genetically modified organisms and biohazard materials related to the research properly. Specifically, Daiichi Sankyo has established an internal biosafety manual that includes rules for the safe handling of pathogens and pathogen-containing materials in order to handle them safely and complies with the laws and regulations concerning these biohazard materials including “the Act on the Prevention of Infectious Diseases and Medical Care for Patients with Infectious Diseases” and “the Act on Domestic Animal Infectious Diseases Control”. The Biosafety Committee determines the proper operating rules for handling biohazard materials. Daiichi Sankyo has formulated internal rules for recombinant DNA experiments to ensure that genetically modified organisms are managed appropriately in accordance with the Cartagena Act on Biosafety*4. Furthermore, the Recombinant DNA Safety Committee checks all research protocol to ensure compliance with the Cartagena Act on Biosafety prior to commencement.
Furthermore, we endeavor to take preventive measures against accidents in experiments and breach of laws by requiring researchers who are engaged in these research activities to receive education on the containment of recombinant DNA experiments that are provided by the APRIN, as well as in-house education each year.
*4Act 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 conducts clinical trials in accordance with the Declaration of Helsinki that defines the standards for ethical medical research involving human subjects, while also adhering to ICH-GCP (Good Clinical Practice from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) and complying with the applicable regulations of relevant countries. This means that clinical trials are only conducted after obtaining voluntary informed consent from participants.
All clinical trials sponsored by Daiichi Sankyo are evaluated in terms of ethical standards and scientific validity based on internal review processes. In particular, we ensure that our first in human study is an appropriate through clinical trial review meetings that include employees who are qualified physician as review members. Furthermore, clinical trials are conducted after an external independent committee (Institutional Review Board / Independent Ethics Committee) also reviews the same content (human rights of trial subjects, etc.) and approves the conduct of clinical trials.
Daiichi Sankyo provides training programs on GCP and Ethics related to clinical trials to people who are engaged in clinical trials.
R&D & PV Quality Assurance Department conducts audits of the Company’s clinical trial activities to promote appropriate correction and preventive measures.
Collaboration with Contract Research Organizations
Daiichi Sankyo has defined the Global Policy of Clinical Trials Standards and ensure the highest degree of respect for the human rights and well-being of all individuals participating in clinical trials. At the same time, we guarantee that our clinical trials are ensured scientifically high quality, reliable and ethically sound. We also plan and conduct all clinical trials in accordance with GCP and in compliance with local regulations in each country.
In case of that Daiichi Sankyo outsources part or all of clinical trial activities to contract research organizations (CROs), Daiichi Sankyo policies and standards for clinical trials are applied. For this reason, we assess CROs as part of the selection process to determine if they have the necessary capabilities to perform clinical trials and CROs are selected based on the results of assessments. Daiichi Sankyo requires the CRO staff to be trained on Daiichi Sankyo policies and standard procedures. After contracts have been executed, we continue monitoring their performance on a regular basis, as well as maintaining oversight of their services. Our R&D & PV Quality Assurance Department conducts independent audits to determine whether clinical trial services are appropriately outsourced to CROs.
Disclosure of Clinical Trial Information
Daiichi Sankyo registers and discloses all Daiichi Sankyo sponsored Phase 1 to Phase 4 clinical trials on public clinical trial information disclosure websites such as ClinicalTrials.gov, EU-CTR, and JapicCTI in accordance with the regulations of relevant countries and the Guidelines and Principles of industry groups.
Our clinical trial information is also disclosed on the clinical trial information disclosure page of our corporate website
In addition, we provide the environment where external researchers can access to clinical trial data of products that obtained approval in Japan, Europe, and the U.S. under a defined process through a clinical trial data sharing platform (vivli.org).