About Ono

Manufacturing

Enhancing Product Value through the Stable Supply of High-quality Pharmaceuticals

At ONO, all divisions involved in manufacturing cooperate closely with each other and consistently maintain a strong sense of responsibility and ethics as they faithfully practice scientific evidence-based manufacturing according to the operating procedures, and continuously make maximum efforts towards the stable supply of high-quality pharmaceuticals. We are committed to strengthening our capabilities in terms of both “hardware” and “software” related to manufacturing activities for the stable supply of pharmaceuticals.


Initiatives to Ensure the Stable Supply of High-quality Pharmaceuticals


As a health and life science business, it is essential for us to improve productivity to achieve a stable product supply. ONO continually reviews its production systems and invests appropriately in plant and equipment for further optimization for marketed products, while keeping in mind the timing of launching, production volume and product features relevant to the production system structure for products destined for market launch. We also consistently perform cost management encompassing the entire manufacturing process including production of active pharmaceutical ingredient and finished products, as well as managing the costs of raw materials and labeling/packaging materials starting from the supplier selection.

We ensure that all pharmaceuticals are manufactured, whether in-house or through outsourcing, under an appropriate quality assurance system. ONO’s plants have a quality assurance system in place that is compliant with global regulations such as cGMP and PIC/S GMP. In outsourcing production, ONO verifies through regular quality auditing, that appropriate manufacturing control and quality control are implemented We take various measures to ensure the stable supply of high-quality pharmaceuticals, including education and training for all personnel involved in production and quality assurance, strengthening the quality management system in accordance with the ICH Q10 Pharmaceutical Quality System, and upgrading risk management systems at our manufacturing sites.


Quality Management System

We manufacture products while confirming their quality during the entire process of manufacturing. As for the raw materials ONO uses for production, we assess the risks that raw materials may pose to product quality. Suppliers of high-risk materials are required to be confirmed on that they can produce materials that fulfill our product quality requirements before we approve the suppliers. The approved suppliers are re-evaluated at an interval of two to five years according to the level of quality risk, and re-qualified if deemed to meet our criteria. ONO conducts acceptance tests for each lot of raw materials delivered by these suppliers. After we have confirmed that the raw materials satisfy the prescribed quality standards, we use them in manufacturing.

ONO manufactures its products following the prescribed procedures, while checking the product quality at each process of the manufacturing, according to the level of quality risk. As one example, we verify the quality of tablets during the manufacturing process as in-process control from the viewpoint of the quality risk (weight, hardness, thickness, appearance, etc.) that lead directly to the tablet’s efficacy and safety. The method and frequency of these in-process control are established for each item and managed in an appropriate manner.

To develop a manufacturing process that enables us to manufacture a pharmaceutical of the same quality even if the process is repeated tens of thousands of times, we carry out a validation before establishing the process. Production personnel receives training on the prescribed procedure, and is permitted to be engaged in manufacturing operation only after understanding the procedure.

Products that have been manufactured through the manufacturing process are subject to a final confirmation at the quality unit independent from production. Those in charge of quality confirmation are evaluated each year as to whether they can perform appropriate quality tests, and only those who meet the criteria of the qualification are permitted to conduct the quality tests.

In selecting contract manufacturing organizations (CMOs), we evaluate candidates on whether they can conduct outsourced work in compliance with our quality standards, and those satisfying the standards are qualified as our approved CMOs. The approved CMOs are re-evaluated at an interval of two to five years according to the level of quality risk, and re-qualified if deemed to meet our standards. To conduct outsourced work, ONO supplies active pharmaceutical ingredients after their quality has been evaluated. As for other raw materials, their quality is evaluated by the CMOs based on the relevant quality agreements, and ONO checks how this evaluation is implemented through quality auditing by Ono.


Training System

New employees assigned to a plant receive about two months of classroom lectures and on-site introductory training, in order to learn the basics of GMP. They then take on-the-job training at each worksite. According to their proficiency level, these trainees are qualified as Level 2, at which they are permitted to do the work when attended by a skilled worker, or Level 3, at which they can do the work by themselves.
Moreover, we establish an annual training plan for all plant employees, and based on that plan, then, we educate them on the relevant laws and regulations such as the Pharmaceutical and Medical Device Act and the GMP ordinance, the internal rules necessary for manufacturing, and procedures required for production and testing (hereinafter referred to as “GMP education”). This plan covers not only training at plants, but also education conducted by the Corporate Regulatory Compliance Safety and Quality Assurance Division. In fiscal 2018, we held a training program on the importance of quality assurance and recording. Apart from the above training, we also provide training to persons in charge when a standard operating procedure (SOP) is revised, or as the need arises.


Training held in fiscal 2018

Content No. of sessions scheduled No. of sessions implemented
GMP education At least three times
(Scheduled by the section in charge at the start of the fiscal year)
Four to eight times
Importance of quality assurance and recording — Fostering a quality culture Once a year One time
Training regarding revisions of SOPs Every time an SOP is revised 794 times

As for education for employees of our all CMOs, we check the implementation status during quality auditing.

Fujiyama Plant(Shizuoka)

Yamaguchi Plant

Enhancement of Production Systems

ONO has a manufacturing plant, Fujiyama Plant, which is compliant with GMP in Shizuoka. Fujiyama Plant proceeds with continual improvement of its facilities. In addition, a new plant (Yamaguchi Plant) which is compliant with GMP has been constructed in Yamaguchi to mitigate the risk of a major disaster from a business continuity perspective as well as strengthening our production capabilities aimed at future business expansion. Equipped with a production line for highly-potent substances and antibody pharmaceuticals, Yamaguchi Plant started to produce injections at the end of March 2020.


Plant Location GMP
Fujiyama Plant Shizuoka Prefecture Compliant
Yamaguchi Plant Yamaguchi Prefecture Compliant

Safety and Quality Assurance

Enhancing Product Value Through Drug Reliability Assurance Activities

From a patient standpoint, ONO conducts drug reliability assurance activities with global perspective through drug life cycle to constantly check for drug quality assurance and reflect opinions from healthcare professionals and patients on further quality improvement. In addition, we analyze and assess, based on latest scientific evidence, drug quality and efficacy and safety (adverse reaction) information collected from, e.g., reports from patients and healthcare professionals, literature, and surveys, to constantly provide updates to the frontline of healthcare


Quality Assurance Policy

We not only meet the legal requirements as a marketing authorization holder, but also set out our own quality manual to establish a drug quality system and work to continuously improve systems so as to provide high-quality drugs from the viewpoints of patients, caretakers and healthcare professionals. In addition, we contribute to society through stable supply of pharmaceuticals that are assured to a high-quality standard.


Initiatives for Proper Use of Pharmaceuticals

We develop a risk management plan and collect and manage safety (adverse reaction) information for each pharmaceutical. We assess collected data and information, and if necessary revise the cautions on package inserts and make announcements about proper use. As safety information drastically increases inside and outside Japan after market launch of antineoplastic drugs, we assess such information based on opinions from external medical experts to promote the proper use of the drugs, e.g., by disseminating it through promotional materials, conference presentations, and medical journals. In addition, the Corporate Regulatory Compliance Safety and Quality Assurance Division, containing a section responsible for data, also uses and utilizes medical databases to analyze pharmaceutical product profiles and safety information for proper use.


Maintenance of Product Recall System

We have a system in place to recall any products with efficacy, quality or safety problems and to promptly provide medical professionals with information on them. We also have relevant departments jointly conduct periodical drills in preparation for product recall to check that they can be executed quickly even in unexpected circumstances.