An internet-based questionnaire survey was conducted to evaluate effectiveness of an additional risk minimization activity in the Risk Management Plan (RMP), an information material of Xofluza (baloxavir marboxil) for patients, in terms of receipt and understanding of the material and implementation of countermeasures according to the material. The result showed that high percentage of parents who received and read the material took countermeasures to minimize the risk. At the same time, various and practical challenges from the viewpoints of the contents as well as the procedure of the survey came out. Risk minimization activities are planned and conducted to ultimately secure and enhance safety of patients, and there is no question about the necessity of checking whether the activities are actually accomplishing their original purpose. However, the process and methodology have not been established, and we need to deepen our consideration of them based on the accumulating information and experience along with the implementation of the RMP scheme.

The aim of the study is to explore the differences of physical properties and cost evaluations between a brand-name product and 4 generic products of latanoprost/timolol combination eyedrops. A squeeze force which is needed to make one drop, a weight of one drop and the total number of drops were measured by a Digital forcegauge (ZTS-500N, IMADA Co., Ltd). A cost of one drop was calculated based on a drug price of each product. The maximum weight of one drop was 27.13 mg of the brand-name product, which was significantly heavier than those of all the generic products (p<0.01). The squeeze force of the brand-name product was 3.05 N, while those of generic products ranged from 2.75 N to 7.24 N. The minimum of the total number of drops was 104 of the brand-name product, which was significantly fewer than those of all the generic products (p<0.01). A cost of one drop of the brand-name product was 24.42 Japanese Yen (JPY), while that of generic products ranged from 10.17 to 10.71 JPY. Since the total number of drops exceeds 100 in all the products, it is assumed that a drug solution will remain after the expiration date. Therefore, it is suggested to reduce the total amount of the drug solution in each product. Though a product with a small squeeze force is easy to be applied, it has a concern of dripping. A further study is needed to investigate the relationship between dripping and feeling of use of these products.

Pigment exposure and surface roughness have long been concerns regarding health hazards of cosmetic contact lenses. However, apart from Z-stack analysis, no effective method for the depth measurement of pigments exists. In this study, the development of a quantitative method to measure pigment depth at high resolution and the utility of electron microscopy are examined. The samples were prepared according to conventional methods for transmission electron microscopy observation of biological materials. As there is almost no difference in electron density between the resin that constitutes lenses and embedding resin, labeling methods were examined using scanning electron microscopy (SEM) to visualize the surfaces of lenses in the embedding resin. The boundaries were clearly visualized using platinum/palladium (Pt/Pd) sputter coating after freeze-drying. A clear correlation was observed between the results measured by scanning transmission electron microscopy (STEM) and Z-stack analysis. The results indicate that no morphological changes corresponding to the resolution of Z-stack analysis occurred as a result of our preparation method. Pigment depths were analyzed using STEM and the surface-to-pigment distances ranged from 36.9 nm to 18.7 μm for the specimens used in this study. The use of STEM facilitates the measurement of pigment distributions below 100 nm, which cannot be analyzed using Z-stack analysis; this method was able to measure lengths ranging from sub-mm to sub-nm scales. This method has the potential to be a powerful tool to assess the causal relationship between the product quality of cosmetic contact lenses and related health hazards.

Japan’s population is rapidly declining and the aged population will predominate within 20 years. Therefore, maintaining a strong financial, health and welfare is an urgent issue. Japan’s population will continue to decrease, and the number of elderly people will reach its peak around 2040. By 2040, the total population is expected to decrease to 110.92 million, with 1.4 productive age persons per elderly person. In addition, the national medical care expenditure, which is part of the social security benefits, is expected to increase approximately 1.7 times, from 39.2 trillion yen in fiscal year (FY) 2018 to 66.7 to 68.5 trillion yen in FY2040. In recent years, innovative drugs have been developed and approved for patient care, and the use of these expensive drugs has increased medical costs. In general, the prices of new pharmaceuticals without similar drugs are calculated by the cost accounting system on the basis of manufacturing costs, sales costs, research costs, distribution costs, and so on. In this review, we consider how pharmacists contribute to reducing medical costs to ensure the sustainability of the aging society, focusing on the cost structure of pharmaceutical companies in the drug pricing system in Japan.

Application of big data on human health, medical care, and scientific findings to health care has been accelerated by artificial intelligence (AI). Various types of healthcare devices using AI have been developed. Under the current regulatory framework, modification of medical devices is classified into minor or partial changes required for notification of the change or application for change submitted to the regulatory body, respectively. Thus, the characteristics of medical devices change in a step-by-step manner in the post-marketing phase. In contrast, the performance of AI-driven medical devices has the potential to change continuously through the application of real-world data in the post-marketing phase. The present regulatory framework for post-marketing changes to medical devices sets out step-by-step changes, but not continuous changes, while on the market. A new regulatory framework for innovative medical devices with continuous changes in their performance has been discussed by the Health Science Council of the Ministry of Health, Labour, and Welfare since 2018, and the revision of the Pharmaceutical and Medical Device Act sets out this regulatory framework. In this review, a concept for the regulatory review of AI-driven innovative medical devices is described.

Pharmaceuticals and Medical Devices Act (PMD Act) regulates the pharmaceutical products including drugs, medical devices and other related products, and strictly controls new product development, review and approval processes, manufacturing, and post-marketing studies. To achieve medical innovations, researchers in academia as well as those in pharmaceutical industry should be well informed about pharmaceutical regulations and are required to comply with regulatory requirements when conducting preclinical and clinical studies for medical product development. In recent years, academic research organizations (AROs) have been established as university-based organizations that support throughout the process from basic research to practical application, in particular, guiding clinical research and trials in order to promote the development of new pharmaceutical products using academic research findings. Especially in the open innovation model, universities are expected to play an important role. At Osaka City University, we have expanded various research-related ARO functions and services with the catch phrase “Those who master regulation achieve innovation.” In this article, we introduce the institution profile, services and functions of Center for Clinical Research and Innovation (CCRI), an ARO housed in Osaka City University Hospital, and its initiatives to produce innovations from academic research. Academia’s involvement in regulations that interpenetrate with innovations is also discussed.

Approx. twenty years have passed since the last revision of the “Guidelines for Toxicity Testing of Pharmaceuticals” in Japan. In International Conference on Harmonization (ICH), new guidelines have been issued and some existing guidelines have been revised, but the contents described in the new and the revised guidelines have not been reflected in “Guidelines for Toxicity Testing of Pharmaceuticals”. Therefore, the Non-clinical Evaluation Committee, Drug Evaluation committee, Japan Pharmaceutical manufacturers Association proposes the draft revision that incorporates the contents of the new ICH guidelines, animal welfare issues, and scientific advances, namely the “Guidelines on General Toxicology Studies of Drugs (Proposal)”. The authors wish this manuscript is a trigger for revision of the guideline.

Regulatory authorities in Japan and US, i. e., PMDA and FDA, have mandated the submission of electronic data according to CDISC standards at the time of new drug application. That has had a major impact on the Japanese pharmaceutical industry. The world-wide data standards for clinical trial data, i. e., CDISC, should bring significant benefits for us, i. e., 1) reusability, 2) interoperability, and 3) an ability to integrate data from different sources and obtain a knowledge beyond a single clinical trial. However, the industry has not fully reaped such benefits. This is mainly because currently we are spending a lot of resources on converting data from completed clinical trials, which did not comply with CDISC standards, into CDISC-compliant data. We should move away from the data conversion just before the new drug application and hasten the end-to-end implementation of the CDISC standard. What we, the pharmaceutical companies, expect from PMDA is that PMDA will conduct many regulatory science studies, which is possible only with accumulated data, and that PMDA will continue to provide feedback to companies and researchers who are developing drugs, and that PMDA will continue to disseminate useful information to the world.

Each organization has been working on the standardization of the CDISC compliant data creation process toward “Electronic Submission of Study Data for New Drug Applications” after April 2020, and those experiences have been accumulated. However, there are cases where rework sometimes occurs due to differences in policies of the procedures and quality standard among organizations and persons in charge. Therefore, it can be said that there are still remaining challenges in the process of forming a common understanding on both sides of the sponsor/CRO before the start of outsourced work. From the questionnaire survey results on the internal systems and issues for Electronic Study Data Submission support services, which were carried out on the member companies of the Japan CRO Association, it was confirmed that standardization of the CDISC data creation process generally contributed to operational efficiency. On the other hand, the types of work that had not been standardized at that time, such as Electronic Study Data Submission support and clinical pharmacology, became clear as well. To address this situation, Japan CRO Association CDISC Team examined considerations to provide high-quality Electronic Study Data Submission-related services efficiently, as well as to standardize its processes on each side of the sponsor and CRO. Items to be checked at each stage of work have put together in our checklist for building a smooth relationship between sponsor and CRO, so that it can be used to define scope of outsourcing work, division of roles, and agreement of required quality, and to reflect them in operation procedure.

Clinical Research Data Center, Tohoku University Hospital, has been introducing the CDISC standard into its quality management processes since FY2013. In this article, especially based on the experience of participating in the pilot project requiring CDISC Standards of PMDA, we will explain our approaches to promote the CDISC standards and also mention future issues.

PMDA started accepting electronic submission of study data for new drug application in October 2016 and the transitional period for submitting electronic study data was ended on March 31, 2020. PMDA had taken necessary measures such as revisions to notification, toward the end of the transitional period. PMDA’s consultation service related to the submission of electronic study data has been conducted since May 15, 2015. The number of consultations reached 387 by March 31, 2020 and tends to increase each year. After the start of submission of electronic study data, 116 electronic study data were submitted by March 31, 2020, and PMDA has been using the electronic study data submitted in the approval review of new drugs. In addition, PMDA is considering such as analysis of integration of cross-products information of accumulated electronic study data. After the transitional period ends, if necessary, PMDA will take measures such as revisions to notification, based on the submission status of the electronic study data.

PMDA established Asia Training Center for Pharmaceuticals and Medical Devices Regulatory Affairs (PMDA-ATC) in 2016. This Training Center has been providing the trainings for regulators in Asia and around the world based on the accumulated knowledge and experiences of PMDA. The contents of the trainings are wide ranging from basic to practical. The examples of basic lectures include information necessary to build regulatory capacity in each country/region such as international standards/guidelines, benefit/risk evaluation of the medical products, post-marketing safety measures and so on. The mock Good Manufacturing Practice (GMP) inspection seminars at manufacturing facilities are very practical and provide very valuable experience for GMP inspectors in the world. The PMDA-ATC seminars would promote capacity building and human resource development through trainings, and contribute to universal health coverage through developing a foundation for regulatory harmonization in Asia and around the world. The activities of PMDA-ATC has been recognized and highly evaluated internationally. We would summarize the PMDA-ATC activities and its achievements so far, and describe the approach in the future.