The present study aimed at analyzing the factors that were associated with delays in the development of new drugs in Japan by investigating the approval status and timing of new drugs in the US, EU, and Japan, including unapproved drugs in Japan, and discussing measures to prevent such delays. We studied new active substances (NASs) that were approved in both the US and EU between 2010 and 2020, and were approved in Japan later than both country/region or were not yet approved at the end of 2020. Cox regression analysis was conducted using the time from the approval in the US and EU to the approval in Japan as a response variable (unapproved drugs in Japan at the end of 2020 were handled as censored data), and eight explanatory variables such as the availability of similar drugs and whether the drug was antineoplastic. The analysis suggested delays in development in Japan for new drugs for which no similar drug existed or the marketing-authorization holder in the US or EU did not have a Japanese subsidiary. The analysis based on drugs approved in Japan suggested that there might be delays in approval in Japan for NASs for which the originator and the marketing-authorization holder were different, or the expected sales in Japan was small. Based on the result, it is important to consider measures to deal with the issue of drug lag from multiple perspectives including pharmaceutical regulations and drug price system.

The governor’s recognition system for Community Collaborative Pharmacy and Specialized Medical Institution Cooperating Pharmacy has launched in August 2021. The objective of this study was to analyze the data regarding functions of each pharmacy and explore how much pharmacies satisfied the requested functions as a Community Collaborative Pharmacy by each medical district in Chiba Prefecture. The analysis utilized the pharmacy function information of pharmacies in Chiba Prefecture, covering 2,405 pharmacies in 2019 and 2,430 pharmacies in 2020. Items being subjects for the analysis were referred to the certification standards for Community Collaborative Pharmacy. Of all the items, the certification standard with the lowest achievement rate was “results of reporting to and communicating with pharmacists working at medical institutions in the region,” which was achieved by only 2.3% (57 pharmacies) of all the pharmacies in Chiba Prefecture in 2020. There are also few pharmacies that have a system for dispensing sterile products, and only 87 pharmacies (3.6%) of all the pharmacies in Chiba Prefecture had their own sterile dispensing rooms in 2020. A logistic regression analysis was conducted to examine factors associated with the implementation of home-visited pharmacy services. The results showed that the four factors were associated with the implementation of home services: “having a system for dispensing narcotics”, “having a system for dispensing sterile products”, “being a health support pharmacy”, and “being able to use an electronic version of the medication handbook”.

Healthcare professionals are required to recognize the onset of adverse drug reactions in patients, and make attempts to prevent them in advance. Here, we conducted a study to test the hypothesis that active use of a questionnaire titled “Adverse Drug Reaction Signal Check Sheet” makes it easier for pharmacists to collect information on symptoms experienced by patients. The questionnaire classifies subjective symptoms into eight items. We surveyed patients on high-risk medication from 93 pharmacies that cooperated with the study. First, we implemented a questionnaire that involved a pharmacist listening to complaints of patients with subjective symptoms during routine medication instruction (Survey ①). Next, the presence or absence of subjective symptoms was checked using the “Adverse Drug Reaction Signal Check Sheet” during routine medication instruction by comparison with the contents of the previously completed questionnaire (Survey ②). In addition, we conducted a post-facto questionnaire on pharmacies that cooperated with the survey (Survey ③). Statistical analysis was conducted using the Wilcoxon signed rank test. 51 pharmacies responded to Surveys ① and ②. (Response rate: 54.8%) 92 pharmacies responded to Survey ③. There were 18 cases of subjective symptoms reported by 17 consulting patients in Survey ①. There were 238 cases of subjective symptoms reported by 169 consulting patients in Survey ②. The number of cases of subjective symptoms detected between Survey ① and Survey ② was aggregated for each pharmacy and compared, and a statistically significant difference was observed (p<0.001). The results suggested that presentation of the “Adverse Drug Reaction Signal Check Sheet” provided an opportunity for patients to consult pharmacists about subjective symptoms. Although subjective symptoms are thought to include symptoms due to underlying diseases and indefinite complaints that are not adverse drug reactions from medications, it is necessary to be aware of the medical history of the patient, including the presence or absence of symptoms before the patient is aware of them to identify changes in a patient’s physical condition before and after medication.

With the aim of recognizing the effect of recent drug pricing reforms in Japan on the global development strategy of new drugs, the state of Japan’s participation in multi-regional clinical trials (MRCTs) sponsored by major foreign-affiliated companies was investigated based on the information registered in ClinicalTrials.gov. While the number of MRCTs sponsored by the major foreign-affiliated companies has been nearly constant in the past decade, the number and proportion of MRCTs in which Japan participated have steadily increased. The proportion of Japan’s participation seemed slightly decreased in 2021, and it needs a longer follow-up to judge whether it is a temporary phenomenon. The state of Japan’s participation in MRCTs sponsored by major foreign-affiliated companies would serve as an appropriate indicator of any change in Japan’s position and investment priority in global new drug development, and it needs to be investigated continuously in the future.

A cost-effectiveness evaluation system has been introduced in April 2019 for price adjustments of new health technologies. At the same time, a specialist development program for health technology assessment has been started at Keio University and dozens of people have completed it. In this paper, we held a workshop (Mock pre-discussion meeting) to set up a simulated cost-effectiveness analysis framework for program students. We report a summary of the issues from the workshop using the three products in the H1 and H2 categories evaluated as of October 2021.

The SaMD Forum was held on February 4, 2022, bringing together innovators and administrative officers, regulation staffs. The purpose of the forum was to promote the early commercialization of SaMD by establishing an examination system and structure that takes into account the characteristics of SaMD. At the forum, discussions were held among the parties concerned from three perspectives: research and development, regulatory review, and reimbursement pricing. There are four points that the author believes will be the subject of future work. The first is the issue of “endless software updates on post-marketing,” the second is the issue of “achievement criteria and the necessity of clinical trials,” the third is the issue of the concept of “prescribing of information,” and the fourth is the issue of “Innovation Assessment”. SaMD is evolving at an extremely rapid pace, and new issues will continue to emerge in the future. Therefore, it is important to continue discussions from the demand side among stakeholders through the continuous holding of the forum.

In addition to software with tangible medical device, software itself has been defined as medical device since PMD Act amended in 2013. In addition, medical device software classified as Class I is not subjected to restrictions on the PMD-Act. To review SaMD, it is important to determine the role of the SaMD in clinical practice. The role of the software affects whether the software is medical device or not, and how we review. Effective regulatory pathway, consultation service for good communications with applicants and discussion with experts are necessary for regulators.

Software as medical devices (SaMDs) are used in the current medical field. It is recognized as indispensable for the continuation of medical care. In 2020, SaMD that the patient directly operates to support treatment was put into practical use. It is expected that more and more SaMDs will be used in the medical field in the future. In the FY 2022 Medical fee revision, the ideal way of evaluating medical insurance for SaMDs was discussed. It is expected that not only medical device marketing approval holders but also pharmaceutical companies and start-ups will develop SaMDs. We hope that the developers of SaMDs will be able to think about insurance strategy for the products under development. This paper outlines the discussion on SaMDs in the FY 2022 Medical fee revision.

This document introduces the importance of Software as a Medical Device (SaMD) using digital technology, which is undergoing rapid technological innovation to solve social issues in our country, and METI’s support for it. METI has been initiatively attempted to encourage the research and development for SaMD, for example, the establishment of a centralized consultation service, consulting by experts, execute the research and development subsidies, formulating the guidelines, and inform the dissemination. We believe that the necessary of SaMD will increase in the future influenced by the necessity of operational efficiency and reformation of the work styles in the medical field. We will contribute to improve the environment of research and development to promote the innovative medical devices based on their social value, and we will also cooperate with other ministries and industries to establish the rules to ensure the safety of novel medical devices. Finally, we concluded by indicating that our expectations for SaMD are also reflected in the five priority areas of medical devices must be supported to effective research and development listed in the Second Basic Plan for Medical Devices, which was approved by the Cabinet in May of 2022.

Today, many medical devices have already been developed, supported by digital technology. Among such devices, this article focuses in particular on Software as a Medical Device (SaMD) and Digital Therapeutics (DTx). First, the short history of DTx is reviewed, and some notable products, which are developed in countries other than Japan, are introduced as notable examples of DTx. Second, the discussion shifts to the situation in Japanese DTx development, with respect to a lag in comparison to that in overseas. The SaMD/DTx in Japan are suffering from several problematic situations: (ⅰ) uncertain profit projection in the insurance reimbursement system, (ⅱ) limited regulatory information due to lack of accumulation of examples, (ⅲ) difficulty in planning of clinical trials and strategy of post-approval software modification (ⅳ) construction of software logistics and authentication system (ⅴ) increasing non-SaMD software as competitive products. Finally, some desirable future situations and expected challenges in digital healthcare development in Japan are proposed, based on the discussion above. A variety of products, not only SaMD/DTx but non-SaMD, will be developed to create an ecosystem and will be interconnected, enabling total healthcare. To improve product development, the above problem situation should be solved step by step. In addition to them, rulemaking is required for the protection and use of personal health records (PHR). Recently, several SaMD developing healthcare companies in Japan has established a unified industry organization, JaDHA. We expect that the difficult situation will be resolved throughout dialogue among companies, regulatory organization and other all related stakeholders.

The Japanese Pharmacopoeia (JP) 18^th edition was published on June 7, 2021 and its key topics are as follows: (1) implementation of ICH-Q3D; (2) 33 new monographs, (3) one new and five revised general tests; (4) seven new general information; and (5) removal of harmful reagents, and use of the word “enantiomer” instead of “optical isomer;” (6) removal of some alias names (commonly used names), and revision of several titles. This article summarizes the above key topics. In addition, the difference in the basic principles for the preparation of the JP 18^th edition and those of the JP 19^th edition, which was announced on September 2, 2021, are presented.