Stable Supply and Quality Control
Astellas places highest priority on ensuring robust manufacture and stable supply of safe and effective pharmaceuticals to patients. To ensure this, we have established our own standards aligned with Good Manufacturing Practice (GMP) and Good Distribution Practice (GDP) as the basis for consistently achieving high levels of quality. We apply these standards to manufacturing facilities and equipment, and to all stages from raw material procurement and storage to production and shipment.
Astellas is continuously investing in various manufacturing facilities with the aim of maintaining and strengthening stable supply. In 2020, construction of the Center for Active Ingredient for Biopharmaceuticals was completed at Toyama Technology Center. Bio-drug substances for clinical trials and commercial use are manufactured at the Center and supplied according to global standards. In addition, construction of the Third Fermentation Building has commenced. When the construction is completed, the active pharmaceutical ingredients of immunosuppressant Prograf® that suppress rejection after organ transplants will be manufactured at the facility. In Yaizu Technology Center, construction of aseptic drug product manufacturing lines which allow flexibility to manufacture not only antibodies but also new modalities requiring high-level technology in the future was initiated. In the gene therapy domain, Astellas has established plants in South San Francisco, California and Sanford, North Carolina (GMP manufacturing will commence in 2022), building capability for the in-house manufacture and supply of adeno-associated virus (AAV) drug substances, AAV products, and plasmids which provide self-sufficiency from research to the commercialization of gene therapy programs. Meanwhile, in the cell therapy domain, Astellas has established a new manufacturing base in Westborough, Massachusetts, in April 2020, strengthening our capability to manufacture GMP-compliant, cell-based drug substances and products for use in cell therapy. By constructing such in-house, state-of-the-art manufacturing facilities, we aim to build a more robust manufacturing system capable of supplying high quality products going forward.
Astellas has quality systems for auditing both internal sites and external manufacturing and distribution partners. The risk-based auditing approach determines the sites audit frequency and intensity. Internal audits are conducted on all Astellas organizations that conduct current Good Manufacturing Practice (cGMP) and/or current Good Distribution Practice (cGDP) activities at all points across the product lifecycle and across the supply chain, in accordance with documented policies and procedures. Quality audits are conducted for new or established external partners of Astellas. Such audits are performed to evaluate compliance with cGMP, cGDP and applicable Astellas requirements. In fiscal 2022, Astellas performed a total of 444 audits, including 31 internal audits and 413 quality audits of external partners globally.
Supply Chain Management Structure for Stable Supply
Supply chains are becoming more complicated than ever due to the increase in global products and diversification of modality, along with the increase in partnerships and cooperation with suppliers. Taking these environmental changes into account, Astellas is strengthening its supply chain management globally by building a framework to centrally manage demand forecasts, inventory data and supply plans for regions all over the world, encompassing the manufacture of drug substances through to finished product supply.
Moreover, in addition to building a global logistics and distribution network to develop the functions and capabilities which flexibly meet the various needs for products, including cold chains, Astellas is advancing logistics and trade compliance, including for imports and exports, to enhance the stable supply management.
Furthermore, in the area of commercial supply chain, Astellas has established a function at three locations: Japan, the Netherlands, and the US to continuously develop the supply chain process adapting to the environment changes and strengthened the management framework in global operations.
Shared Logistics for Stable Supply
One of the most important missions for a pharmaceutical company is to continuously improve BCP (Business Continuity Plan) and maintain and continue a stable supply of pharmaceutical products even when natural disasters occur. The Ministry of Health, Labour and Welfare released Japanese GDP (Good Distribution Practice) Guidelines which require greater strictness with respect to ensuring quality in storage and shipment under GDP. Meanwhile, MLIT (Ministry of Land, Infrastructure, Transport and Tourism), METI (Ministry of Economy, Trade and Industry), and MAFF (Ministry of Agriculture, Forestry and Fisheries) are promoting “White Logistics,” an initiative aimed at addressing working style reform, driver shortages, CO2 reduction among other issues facing logistics. Under this initiative, consignors cooperate with logistics partners to implement activities for improvement and reform, and build sustainable logistics frameworks.
Under the environment changes surrounding logistics, Astellas, Takeda Pharmaceutical Company Limited, Teva Takeda Pharma Ltd., Teva Takeda Yakuhin Ltd. and Nichi-Iko Pharmaceutical Co., Ltd. have co-established a shared storage and joint distribution platform in Hokkaido, Japan. The platform aims to ensure a diverse and stable supply of pharmaceuticals with adequate contingency, even in the event of a large-scale natural disaster, as well as enhancing efficiency and quality management of product distribution. Astellas will continue initiatives that advance the sharing and standardization of the pharmaceutical logistics within the industry.
The joint distribution platform in Hokkaido has reduced costs. It has not only enabled us to set up a new logistics base but also has reduced the environmental burden through the reduction of carbon emissions. In recognition of these points, Astellas received the Minister of Economy, Trade and Industry Award in 2018 for the Green Logistics Excellent Business Award.
From 2021 onward, a joint distribution center was added in Kyushu, and a system for product inventory and supply management was established at four locations in Japan.
Practice to Responsible Manufacturing for Stable Supply
A stable supply of medicines is necessary for patients to have continuous access to Astellas products. The stable supply requires minimizing the risk of accidents caused by manufacturing. Some drug substances, which are active pharmaceutical ingredients, are synthesized through multiple chemical reactions. As a result, chemical reactions and associated raw materials have many inherent risks that can cause such as fires.
In order to minimize these risks during the manufacturing process, Astellas conducts assessments in at the R&D stage of manufacturing for each drug substance whether there are any risks of accidents such as unusual reactions and fires caused by uncontrolled chemical reactions and static electricity discharge. For example, we understand the decomposition starting temperature of all chemical substances used in the manufacturing and the calorie generated by chemical reactions. In addition, we design proper manufacturing equipment prevents fires. In these ways, we continuously improve our manufacturing processes safer and finalize the processes to deliver VALUE to patients.
This practice is important to ensure that patients have continuous access to Astellas products and treatments through our efforts to create a stable supply via responsible manufacturing practices.
Measures to Prevent Medical Malpractice and to Improve the Distinguishability of Pharmaceuticals
Astellas strives to supply products from the users’ perspective to ensure that healthcare professionals and patients do not mistake one pharmaceutical for another. We are working to prevent medical malpractice in this respect, through measures including printing product names directly on capsules and tablets, as well as printing product names and dosage on packaging sheets (blister sheets) so that the product name and dosage can be easily identified even after the blister sheet is split apart.
To prevent misreading of labeling on blister sheets, Astellas also endeavors to make products easier to identify visually by adopting easily discernible colors and font types for the blister sheets of certain products. We also adopt blister card packaging*1 for pharmaceuticals that require care with dosage frequency from the perspective of preventing medical malpractice. For example, Evrenzo® 20 mg / 50 mg / 100 mg tablets newly launched in 2019 are packaged in a set of three tablets in order to prevent taking more or less than the required dosage of three times per week. The size, color and labeling design are also differentiated to reflect the dosage size, to prevent taking the wrong tablet.
In addition, to improve patients’ medication compliance and ease of swallowing, Astellas is also reducing the size of the tablet and changing the formulation. For example, the XTANDI® 40 mg (10.1 mm dia.) / 80 mg (17.2 mm dia.) tablets launched in 2018 were smaller than the previously released XTANDI® 40 mg (21 mm dia.). Moreover, as the number of tablets per dose is expected to be reduced, it will also reduce patients’ burden when taking medications.
*1 Blister card packaging: Plastic packaging formed to fit the shape of the product.
Introducing Universal Design into Product Packaging
We have introduced universal design to certain product packaging. For example, the universal design packaging of Bonoteo® 50 mg tablets, which is administered once every 4 weeks, features packaging with good openability. To prevent patients from forgetting to take the drug, there is an area provided on the packaging to write the day when the drug should be taken. A small sticker to be used on a calendar is also attached. In addition, the packaging uses a universal design font type for easy reading.
Astellas has established its own quality standards in compliance with current Good Manufacturing Practice (cGMP) and applies these standards to Astellas Group manufacturing sites. In fiscal 2022, Astellas did not undergo U.S. FDA inspections globally.
US FDA inspection history
|FY||The number of FDA Inspections||Warning Letter Issued||Form 483 Issued*2||Location of Form 483 Issued|
* The Norman plant in the U.S was transferred to Avara Norman Pharmaceutical Services, Inc. in August 2016.
*2 Form 483: An FDA Form 483 is issued to firm management at the conclusion of an inspection when an FDA investigator(s) has observed any conditions that in their judgment may constitute violations of the Food Drug and Cosmetic (FD&C) Act and related Acts.
Astellas has set forth the quality assurance function and activities in the Quality Manual. The Quality Manual sits on the apex of the document management system hierarchy. Underneath the Quality Manual, policies, standard operating procedures, and guidelines exist defining quality assurance systems, operational management and procedures for a variety of quality assurance-related activities at the global, regional and national levels. Education and training programs are implemented to promote understanding and awareness of these matters.
These documents are revised periodically and as necessary. We respond swiftly to developments in the external environment, such as regulatory changes and amendments through an established Regulatory Intelligence system.
Strengthening of Quality Assurance Systems at Affiliates
Astellas has developed a robust global quality assurance system so that it can ensure patients worldwide a supply of uniformly high quality of pharmaceuticals. This quality management system was developed to be consistent with our quality policy on a global, company-wide basis. The organizational structure of the global quality assurance system incorporates the quality assurance activities of all Astellas affiliates. Our sales affiliates globally receive ongoing support in strengthening our quality culture whilst educating our personnel to the highest standards.
Efforts toward Environmentally-Friendly Manufacturing through Collaboration with Manufacturing Subcontractors Across-Globe
Astellas is developing environmentally-friendly pharmaceutical manufacturing processes not only for patients, but also for a sustainable society coexisting with communities and nature. The chemical synthesis of drug substances, which are active pharmaceutical ingredients, generally involves the use of environmentally hazardous substances, like organic solvents. Astellas is evaluating the environmental effect of drug-manufacturing processes and taking necessary measures in order to minimize impact.
Recently, Astellas started collaborating globally with subcontractors at the early-stage development of manufacturing processes. In addition, we have also started working on several activities together with our subcontractors to evaluate and reduce environmental impact. These include: sharing our environmental standards, understanding their Environment, Health & Safety policies and manufacturing processes in detail, examining the treatment of environmentally hazardous gas and waste liquids generated during chemical synthesis, planning countermeasures for potential environmental impact. Through these collaborative activities, we are developing manufacturing processes with low-environmental impact.
Astellas strives not only to ensure the quality and stable supply of pharmaceuticals, but also to pursue environmentally-friendly manufacturing of pharmaceuticals all over the world. Through these measures, we contribute to the benefit of patients and environmental preservation on a global scale.
Relationship With Local Communities and Consideration for the Environment
To promote sustainable pharmaceutical manufacturing, Astellas arranges opportunities for dialogue with local residents and communities near its manufacturing sites. By proactively disclosing its initiatives, Astellas is working to build good relationships with them.
On the premises of the Kerry Plant in Ireland, our nature reserve is a resource made available to the local community and visitors by creating public walkways and information boards, provided by Astellas, detailing the flora and fauna and biodiversity in the nature reserve.
Astellas holds an annual calendar art competition with local schools on the topics of safety, environment and energy. Funds raised from the sale of these calendars are donated to a local charity. Each year, over 1,000 entries are received from 12 local schools.
Astellas helps in promotion of STEM (Science, Technology, Engineering and Math) to local schools through science and engineering talks and tours onsite and online. Astellas communicates with the local community with the publication of the quarterly Astellas Biodiversity Newsletter. This newsletter contains biodiversity information relative to the season it is published in. Astellas nurtures good community relationships through integration with and the support of many other local interest groups such as a local nursing home, local Men’s Shed Association, Tidy Towns committee, National Park Education Centre, local bee keepers and local bird and bat conservation groups.
One of industry’s biggest challenges is to develop manufacturing processes that do not unnecessarily burden the environment and to develop sustainably within the local community. The efforts made by Astellas to meet the highest manufacturing standards for our life saving drugs, but also the requirement to do so sustainably limiting our impact on the environment have not gone unrecognized. Since April 2020, the Kerry plant has won SEAI*3 award under the category of Energy Team of the Year.
*3 SEAI: Sustainable Energy Authority of Ireland is an Irish government-affiliated organization supporting the reduction of CO2 emissions.