Compliance with Laws and Regulations and Consideration for the Human Rights of Participants in Clinical Studies

In conducting clinical studies, Ono complies with local regulatory requirements, including Good Clinical Practice (GCP), the Declaration of Helsinki, and the International Council for Harmonisation (ICH) guidelines. Ono conducts clinical studies with the utmost respect for the human rights of clinical study participants and with close attention to their safety. Ono is also committed to protecting the personal information of clinical trial participants and to conducting clinical studies in accordance with the highest ethical standards. In the planning of clinical studies, the feasibility of conducting a clinical study is first examined from ethical and scientific perspectives by the internal institutional review board. A clinical study that has been determined to be feasible by the internal review will be conducted after undergoing a process of review and approval by the institutional review board of the medical institution conducting the clinical trial.

Informed Consent of Participants

Participants in clinical studies are given a full explanation by the investigator in advance about the study objectives, methods, expected benefits and disadvantages, the fact that they can withdraw from the study at any time, and that they will not be disadvantaged if they do not participate, and they give their consent voluntarily (informed consent). If any new information related to the study is obtained, the participants will be promptly informed of the details and their willingness to continue participation in the clinical trial will be confirmed.

Planning and Conduct of Clinical Studies

Clinical study plans are drawn up after thorough consideration from specialist perspectives, including medicine, pharmacy, and statistics. Clinical studies are conducted in accordance with the protocol, which includes the collection of adverse reaction data and risk assessments to ensure the safety of clinical study participants. In addition, Ono regularly monitors clinical studies to ensure that the studies are conducted appropriately in accordance with the protocol and GCP, and if any deviations are found as a result of this monitoring, Ono investigates their causes and take measures to prevent recurrence, thereby ensuring that clinical studies are always conducted appropriately.

Training and Monitoring

In order to ensure that clinical studies are conducted in compliance with GCP and ICH guidelines, Ono provides the necessary training to the employees involved in clinical studies and the medical institutions conducting the study. In addition, Ono also provides training on clinical study protocols and standard operating procedures, and has a system in place to ensure that clinical studies are conducted in accordance with the pre-established study plan and procedures. Even when outsourcing clinical study-related operations to a contract research organization (CRO), Ono confirms that the necessary training is provided to ensure that CRO staff can perform their work in compliance with GCP and other regulations, and conduct regular audits to confirm that the outsourced clinical study operations are carried out appropriately.

Management and Disclosure of Clinical Study Data

Ono believes that sharing clinical study data and results with researchers, healthcare professionals, and patients contributes to the promotion of scientific and medical research and is in the public interest, and Ono discloses the data through external websites in accordance with our “Disclosure of Clinical Study Data Global Policy.” With regard to the personal information of patients who have participated in clinical studies, Ono manages it using legal and appropriate means in accordance with the applicable laws and regulations, as well as our own internal rules, and handle it within the scope of the intended use for which consent has been obtained. Ono also protects the personal information of patients by anonymizing it, etc., when making it public.

For “Disclosure of Clinical Study Data Global Policy”, please see here.

Post-study Access to Investigational Product

In cases where the target disease of the clinical study is a serious one and there is no alternative treatment, the study plan is drafted taking ethical issues into consideration, such as making changes to the study plan to enable the continuation of treatment with the investigational product depending on the medical condition of the participating patients, even after the evaluation of efficacy and safety as stipulated in the protocol has been completed and the clinical study has ended. For example, after obtaining marketing approval from the government, there may be a certain period of time before the investigational product can be prescribed at medical institutions. In such cases, the clinical trial is switched to a post-marketing clinical study and continued so that patients who participated in the clinical trial can continue to receive treatment with the investigational product. In addition, if the investigational product is in the final stage of development, Ono considers conducting a clinical study (expanded access program) in which patients who could not participate in the clinical study can receive the investigational product, in response to requests from medical institutions.

In the process of new drug discovery, research using human specimens (blood, tissue, cells, genes, etc.) will be conducted as an effective means for predicting the efficacy and safety in human. It should be considered essential not only to obtain the donors’ understanding and consent about the necessity and usefulness of such research but to give ethical considerations including strict protection of privacy through proper management of personal information obtained in the course of research. Especially, analytical research on human genome/gene sometimes reveals the genetic predisposition of donors as well as his or her relatives, depending on how the genetic information is handled, various ethical, legal or social issues may arise. Ono also recognizes that the use of human embryonic stem cells (ES cells) for research purposes raises bioethical concerns because human ES cells are derived by destroying human embryos, which are the emerging potential of human life, and they have the potential to differentiate into any type of human cells. Ono believes that we should carefully consider the use of human ES cells for research purposes at an internal ethics committee based on relevant laws and regulations and guidelines.

In order to properly conduct the research using human specimens, Ono has established internal rules based on the National ethical guidelines (“Ethical Guidelines for Medical and Biological Research Involving Human Subjects”). In addition, Ono has established the “Ethics Committee for Research Using Human Specimens" as an advisory committee, and scrutinizes and rules on the ethical and scientific appropriateness of each research plan. This advisory committee comprises internal and external members including experts in the fields of humanities and social sciences, including ethics and law, experts in the field of natural science and person representing the ordinary public interest so that fair and independent review can be made based on an academic as well as multidisciplinary knowledge and viewpoints.

The committee rules, list of members, and summary of the committee’s minutes are made available to the public via “Ethical Review Committee Reporting System” of the Ministry of Health, Labor and Welfare. For above information, please see here (only available in Japanese).

Emerging technologies including the creation of artificial pluripotent stem cells (iPS cells) from human somatic cells and human genome editing for gene therapy have the potential to be applied to the investigation of the causes of diseases and the fundamental treatment of diseases, and we have a keen interest in these technologies. In Japan, basic research to create human germ cells is permitted as long as it meets certain requirements under the “Guidelines for Research on the Derivation of Human Germ Cells from Human iPS Cells or Human Tissue Stem Cells.” However, the creation of human embryos using artificially produced germ cells is prohibited. Ono complies with this guideline and does not conduct research involving the creation of human embryos from artificially produced germ cells.

When utilizing emerging technologies, Ono handles them with care by complying with relevant laws and guidelines and taking ethical considerations into account.

Ono wishes to make a social contribution by developing drugs that support the healthy lives of people. However, in the process of new drug discovery, experiments on laboratory animals are imperative. From the viewpoint of animal welfare, Ono believes that the lives of laboratory animals must be respected and their distress minimized, and that scientifically rational experiments should be conducted with a minimum number of animals.

To this end, Ono follows in-house regulations in compliance with Japan's Act on Welfare and Management of Animals and related guidelines. Before conducting animal experiments, Ono evaluates the target molecules and compounds using in silico and in vitro evaluation models to narrow down compounds to be evaluated in animal experiments. In this way, Ono is implementing the 3Rs^*1 principle of animal experimentation. All animal experimental protocols must be reviewed, whether or not they follow the 3Rs principle of animal experimentation by the Institutional Animal Care and Use Committee, and only the protocols that have been approved can be carried out. Moreover, researchers who conduct animal experiments are required to undergo specialized training every year to learn about Japanese laws and guidelines related to animal experiments, in-house regulations, and the handling of laboratory animals.

To confirm that our animal experiment facilities are in compliance with Japanese laws, guidelines, and in-house regulations, we conduct regular self-inspections and continue to earn accreditation from the Center for Accreditation of Laboratory Animal Care and Use^*2. In addition, Ono holds an animal memorial service every year to express our gratitude to the animals and to wish them peace of mind.

*1　3Rs

Replacement: methods that utilize alternative methods for non-animal experiments

Reduction: methods that minimize the number of animals used

Refinement: methods that avoid unnecessary distress to animals

*2　The Center for Accreditation of Laboratory Animal Care and Use is an organization within the Japan Pharmaceutical Information Center that conducts third–party inspections and evaluations of animal experimentation and other work at animal testing research institutions under the jurisdiction of the Ministry of Health, Labour and Welfare. The Center for Accreditation of Laboratory Animal Care and Use determines whether such facilities are conducting appropriate experiments based on a scientific perspective, while promoting voluntary ethics management of animal testing programs and consideration of animal welfare.

https://www.japic.or.jp/calac/english.html

Ono uses genetically modified organisms for purposes such as new drug research and development, production of antibodies and proteins, and cell therapy research. Ono prevents the spread or leakage of genetically modified organisms into the environment by complying with our internal regulations based on the “Act on the Conservation and Sustainable Use of Biological Diversity through Regulations on the Use of Living Modified Organisms” (Cartagena Act). In addition, to promote the appropriate use of these research samples, the in-house committee for biosafety continues to provide education and training to laboratory staff and conduct examinations on the experimental applications.