Enhancing Product Value through the Stable Supply of High-Quality Pharmaceuticals
To ensure stable supply of high-quality pharmaceuticals, ONO faithfully practices scientific evidence-based manufacturing with a strong sense of responsibility and ethics while maintaining close collaboration with all departments involved in manufacturing. We are also working to strengthen our manufacturing systems and capabilities in terms of both hardware and software for more stable supply of pharmaceuticals.
Initiatives to Ensure the Stable Supply of High-Quality Pharmaceuticals
As a company in the health and life sciences industry, it is essential for us to improve productivity to maintain a stable supply of products. As part of such efforts, we continually work to optimize our production systems and make appropriate investments in plant and equipment. For products to be newly marketed, we design an optimal production system, taking into account a sales start date, production volume, and product features, and for already marketed products, we review and reconfigure the production systems and processes to further improve production efficiency. Furthermore, we implement integrated cost management, from active pharmaceutical ingredient (API) production through to commercialization. We also strictly manage costs of raw materials and labeling/packaging materials from the supplier selection stage.
We ensure that all pharmaceuticals are manufactured, whether in-house or through outsourcing, under an appropriate quality assurance system. All our plants have a quality assurance system in place that complies with international standards, such as cGMP and PIC/S GMP. In outsourcing production, we confirm, through regular quality audits, that appropriate manufacturing control and quality control are implemented. We take various measures to ensure a stable supply of high-quality pharmaceuticals. Such measures include providing training to all employees involved in production and quality assurance, strengthening the quality control system in accordance with the ICH Q10 Pharmaceutical Quality System Guidelines, and upgrading the risk management systems at our manufacturing centers.
Quality Management System
We manufacture products while performing quality checks at every step of the manufacturing process. For raw materials used in our production, we assess the risks that raw materials may pose to product quality. For raw materials with high quality risks, we select suppliers through a rigorous screening process. We evaluate potential suppliers carefully and select only companies with the capability to produce raw materials that meet our stringent quality requirements as certified suppliers. Certified suppliers are re-evaluated at an interval of two to five years according to the level of quality risk and are re-certified if deemed to meet our criteria. Upon receiving raw materials from the suppliers, we perform acceptance tests in-house for every lot, and raw materials are used in manufacture only after they are confirmed to meet the prescribed quality standards.
At ONO, all products are manufactured in compliance with the prescribed procedures while checking quality at each stage of the manufacturing process according to the level of quality risk. For example, for quality testing conducted during the tablet manufacturing process, the methods and frequency of assessing the quality risks (weight, hardness, thickness, appearance, etc.) that lead directly to the tablet’s efficacy and safety are defined and documented for each item to ensure proper quality management throughout the manufacturing process.
Also, prior to beginning regular production, we conduct process validation to ensure that our manufacturing process is capable of consistently producing pharmaceuticals of the required quality even if the process is repeated tens of thousands of times, and based on the results of the validation, we define manufacturing procedures. All members involved in production receive training on the prescribed procedures, and only those who understand the procedures are allowed to be engaged in manufacturing operations. All manufactured pharmaceuticals are subjected to final quality inspection by the quality department, which is independent from the manufacturing department. Those in charge of quality testing are evaluated each year to determine whether they can perform quality testing properly, and only those who meet the criteria are allowed to perform quality testing.
The duties of the quality department include examination of the records related to manufacturing and testing, change and deviation management, document management, including establishment and revision of procedure manuals, and confirmation of training implementation status. In selecting contract manufacturing organizations (CMOs), we carry out quality audits on CMO candidates to confirm that they can manufacture pharmaceuticals that meet our quality standards, and we also evaluate their quality systems as well as manufacturing and quality control systems. Only those that pass our audits are certified as our CMOs.
Certified CMOs are re-evaluated at an interval of two to five years according to the level of quality risk and are re-certified if deemed to meet our criteria. To ensure consistent quality, we supply APIs to our CMOs after conducting quality testing. As for raw materials other than APIs, their quality is evaluated by CMOs based on the relevant quality agreements. We check each CMO’s implementation status in our quality audits.
New employees assigned to a plant receive a two-month introductory training program comprising classroom lectures and on-site training to learn the basics of GMP. After that, they receive on-the-job training at their workplace. Upon completion of the on-the-job training, depending on their proficiency level, new employees are qualified as Level 2, which allows them to perform tasks under supervision of a skilled worker, or as Level 3, which allows them to perform tasks independently without supervision.
We establish an annual training plan for all plant employees. Based on the plan, we conduct training sessions 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 the procedures required for production and testing (hereinafter referred to as “GMP training”). This plan covers not only training at plants but also training conducted by the Corporate Regulatory Compliance Safety and Quality Assurance Division. In FY2019, we provided training on the importance of quality assurance and recording. Apart from the training mentioned above, when a standard operating procedure (SOP) is revised, we provide necessary training to the relevant staff members.
Training held in fiscal 2019
|Content||No. of sessions scheduled||No. of sessions implemented|
|GMP training||At least three times a year
(Scheduled by the section in charge at the start of the fiscal year)
|4 - 12 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||588 times|
We conclude quality agreements with all of our CMOs. Those agreements require the CMOs to provide regular training for their employees. We check the training implementation status through regular reporting from CMOs (once per year) and quality audits.
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.
|Fujiyama Plant||Shizuoka Prefecture||Compliant|
|Yamaguchi Plant||Yamaguchi Prefecture||Compliant|