The 14th Annual Conference of the Regulatory Science Society of Japan Regulatory Science for the Future of Medicine
The 14th Annual Meeting of the Regulatory Science Society of Japan was held at Hitotsubashi Auditorium, Hitotsubashi University (Chiyoda-ku, Tokyo) on September 13-14, 2024, under the theme of "Regulatory Science for the Future of Medicine.
Introduction
The Regulatory Science Society of Japan (RS Society) was established in August 2010 with the founding principle of bringing together people in the medical field, universities, research institutions, industry, and regulatory authorities on an equal footing to openly discuss research results and ideas related to regulatory science for pharmaceuticals and medical devices, and to promote the academic progress and dissemination of such science. The society was established in August 2010. The JPMA has been actively participating in the society by planning and proposing symposiums, supporting the operation of symposiums, and making poster presentations every year in order to discuss systems related to pharmaceutical affairs and their operation with academia, the Ministry of Health, Labour and Welfare (MHLW), the regulatory authority, and the JPMA. We actively participate in the symposium by planning and proposing symposiums, assisting in their operation, and presenting posters.
In 2024, the symposium was held over two days from September 13-14, with active discussions in each section under the theme of "Regulatory Science to Open the Future of Medicine.
The conference consisted of a plenary lecture, three special lectures, one symposium planned by the President, 12 symposia, and general presentations (15 oral presentations and 29 posters).
Symposium 4
Future issues to be addressed in response to the discussions at the "Study Group on Regulatory Framework for Strengthening Drug Discovery and Ensuring Stable Supply of Drugs
Chairperson: Kazuhiko Mori, Executive Director, Japan Pharmaceutical Manufacturers Association
Mr. Yuji Matsukura, Director, Division of Vaccine Examination, Pharmaceuticals and Medical Devices Agency (PMDA), started the session by explaining the background of the study group and the outline of each study as "Future issues and approaches in response to the Study Group on the Drug Regulatory System to Enhance Drug Discovery and Ensure Stable Supply", The report was published in April 2024. He also introduced that the government will promote the elimination of drug lag/loss by formulating policy objectives and a timetable based on the interim report of the "Conceptual Council for Prompt Delivery of the Latest Drugs to the Public through Enhanced Drug Discovery," with the Cabinet Secretariat as the command post.
Next, Mr. Yuji Kashitani, Chairperson of JPMA's Regulatory Affairs Committee, presented "Future issues to be addressed following the discussions at the "Study Group on Regulatory Affairs for Strengthening Drug Discovery and Securing Stable Supply," regarding topics discussed at the study group, including pediatric, orphan, and Japanese P1 before international joint participation, The results of the study group and future issues from the industry's perspective were introduced. Chairperson Kashitani expressed the view that since a direction to go was given at the study group, the PDCA cycle will be used from now on to see if it is being properly operated.
Next, Mr. Shinichiro Takeuchi of the Regulatory Affairs and Development Strategy Department of Aculis Pharma, Inc. gave his opinion on the study group from the standpoint of a start-up company introducing an overseas product in Japan as "Implementation and Issues Following the Study Group on Regulatory Affairs: Issues and Expectations for Measures (Venture Perspective)". The following is a summary of the opinions expressed by the participants. He argued that when a start-up company introduces an overseas product, it is necessary to explain to investors the probability of its sales forecast, development strategy and its costs, and post-marketing activities, etc. Therefore, it is important to clearly state such information in the notice, etc. He expressed his view that in the future, it will be necessary to consider both the prevention of lag loss and the handling of items that have already become lag loss, and that issues such as increasing revenue, post-marketing burdens, and mitigating safe supply risks will become challenges.
Next, Mr. Takeshi Yanagimoto of Boston Consulting Group Japan gave a presentation entitled "Future Vision of Pharmaceutical Regulatory Reform: Considerations from the "Study Group on the Drug Regulatory System for Strengthening Drug Discovery Capability and Ensuring Stable Supply" and explained that the study group was successful because of the expert study group, the declaration to strengthen drug discovery capability in the government's Framework Policy for He introduced that the reason for the success of the study group was that it attracted attention from society due to the issues of stable supply and lag loss. He also expressed his opinion that new drugs of new modalities may cause further lag loss in the future, and that it is necessary to address this issue as soon as possible.
During the panel discussion, there was an opinion that it is necessary to verify whether the notifications issued in response to the study group are being properly implemented by both the companies and the government. It was also commented that it is necessary to consider how to optimize the system in the future, taking into account Japan's international standing. He concluded by saying that the continuation of what was discussed at this meeting is being continued by the Pharmaceuticals and Medical Devices System Subcommittee, which is considering revisions to the Pharmaceutical Affairs Law, and that it is important to keep a future-oriented perspective and discuss the issue when necessary.
Symposium 10
Achieving the Global Standard's Risk-Based Approach to Quality-related Approval Modification Procedures System
Chairperson: Kiyoto Nakai, Director, Drug Evaluation and Control Division, Pharmaceutical Affairs Bureau, Ministry of Health, Labour and Welfare
Chairperson: Yuji Kashitani, JPMA Regulatory Affairs Committee
Ms. Akiko Ishii of the Department of Biopharmaceuticals, National Institute of Health Sciences (NIHS), began the session with a presentation on "Approval Matters in the Manufacturing and Marketing Authorization Documents for Drugs and Guidelines for Matters to be Described in the Application for Manufacturing and Marketing Authorization Documents for Drugs (February 10, 2005; hereinafter referred to as "Guidelines")," as a future direction based on discussions at a pharmaceutical regulatory review committee regarding the approval matters and their change management regarding the quality of pharmaceutical products. (February 10, 2005, Pharmaceutical and Food Safety Agency, No. 0210001), and the FY2023 "Study Group on Regulations for Strengthening Drug Discovery and Ensuring Stable Supply," he outlined the history of approval items and their change management and introduced the discussions at the Pharmaceutical Affairs Regulation Study Group.
Next, Mr. Yoshio Nakayama, a member of the Regulatory Affairs Committee of the JPMA, presented the results of the JPMA's "Fact-Finding Survey on Approval and Change Procedures," which included the actual use of Established Conditions as stipulated in the ICH Q12 Guidelines in the U.S. and Europe, the status of "risk The results of a questionnaire survey on the actual use of the Established Conditions stipulated in the ICH Q12 Guidelines in Europe and the U.S., the awareness of JPMA member companies regarding "risk-based changes," and the perception of the unique Japanese system from the viewpoint of U.S. and European companies (parent companies of foreign companies, partners of domestic companies, etc.) were also presented. He also stated the need to realize an optimal system that can provide a stable and continuous supply of high-quality pharmaceutical products.
Next, Mr. Masahiro Takasuga of the Pharmaceutical Research and Manufacturers of America (PhRMA) introduced the differences in approval items, change management, and change categories in Japan, the U.S., and Europe as "PhRMA's Idea of Approval Item Description and Change Management Related to Quality. The Guideline on Matters to be Described in Marketing Authorization Applications (February 10, 2005, Pharmaceutical and Food Safety Agency Issue No. 0210001) is considered a challenge because it includes items that are not EC items; four categories of changes are considered necessary: prior authorization, notifiable medium risk, notifiable low risk, and no reporting required; and the table format is internationally recognized as an authorization item. The presentation also stated that a tabular format for approval items would be better and easier to understand internationally, and that harmonization with ICH Q12 would be a good idea.
Next, Ms. Yasuyo Ozaki, Chairperson of the Quality & Technology Committee of the European Federation of Pharmaceutical Industries and Associations (EFPIA Japan), gave a presentation on Variation in the EU, examples of Variation in the EU, differences in GMP investigations in Japan and Europe, and the risk-based change system as "Change management in Japan from the perspective of a foreign company in Europe (EFPIA), The presentation was about the risk-based change system. The difference is that in Japan, the change category is set at the time of approval, whereas in the EU, the change category is determined at the time of change, and in the EU, the GMP investigation covers the manufacturing site, whereas in Japan, the investigation covers the product. The EFPIA's opinion was that companies with knowledge and experience should conduct the risk assessment of the change and implement the change.
Next, Mr. Yoshiki Ozawa of the Development Department, Research & Development Division, Sawai Pharmaceutical Co., Ltd. spoke from the standpoint of a generic drug company, explaining that it is desirable to obtain prior agreement on changes after reducing gaps by strengthening communication with regulatory authorities through risk visualization as "the way of change management based on risk and the direction to be taken. He also stated that risk visualization leads to a better understanding of the product and prompt and appropriate change management. While it is desirable in terms of management and operation that the change procedure system be unified globally, especially for brand-name drugs, it was suggested that there could be more than one approach to the same goal of risk-based change management, such as different operations for generic drugs and other drugs not targeted at overseas markets. The opinion was expressed that there could be more than one approach to the same goal of risk-based change management.
Next, Ms. Sonoko Yamauchi, a member of the Regulatory Affairs Committee of the JPMA, gave a presentation on "What is the JPMA's idea of a risk-based change procedure system for approval items? The other is a system in which the procedural category corresponding to the impact on quality and the risk of change is selected at the time of drafting a change proposal, using examples in the guidelines as an indicator. After the explanation of the Japanese risk-based approach and the Western risk-based approach, a presentation was made on the Pros and Cons of each system. He mentioned that there are differences between globally developed products that require international harmonization and products intended for the domestic market. He also proposed a "two-tiered" system in which each product can choose the pharmaceutical affairs system it requires, as well as examples of descriptions in the manufacturing method section as considered by the JPMA.
Finally, Mr. Kazunori Takagi, Director of the Generic Drugs Review Department, PMDA, gave a presentation on the issues currently under consideration, including moderate changes, the annual reporting system, risk assessment and change management, one change in the product switching timing setting, and guidelines on items to be included in manufacturing and marketing approval applications (February 10, 2005, Pharmaceutical and Food Safety Bureau, No. 0210001). A presentation was made. He mentioned the recognition of the issues in setting the categories of changes based on actual production results and knowledge and the guidelines for description in the application form, and stated that it is better to have a pharmaceutical system that harmonizes with overseas systems rather than to introduce foreign systems.
General Abstracts＜Poster
The JPMA Regulatory Affairs Committee made poster presentations on the following three topics
P-1 Emiko Seki (Japan Pharmaceutical Manufacturers Association, Regulatory Affairs Committee, Application Regulatory Affairs Subcommittee)
Current Status of Development Projects at Japan Pharmaceutical Manufacturers Association Regulatory Affairs Committee Member Companies - Considerations from the Status of Global Development Implementation
Emiko Seki, a member of the Regulatory Affairs Committee of the JPMA, and others presented a report on the annual survey of development projects and international clinical trials in Japan since 2011 under the theme of "Current Status of Development Projects by Member Companies of the JPMA Pharmaceutical Manufacturers Association's Regulatory Affairs Committee: Consideration of Global Development Implementation Status". Based on the survey of development projects and global clinical trials in Japan conducted every year since 2011, the trends in 2024, changes over time, and a discussion of more efficient global development strategies were introduced.
For the 2024 survey, responses were received from 66 JPMA Regulatory Affairs Committee member companies. The number of development projects reached 1106, and the proportion of international clinical trials increased to 81%. Antineoplastic drugs were the major development area. Global development items accounted for 92% of the total.
From the timing of the survey, it was inferred that there are still few cases of utilization based on the "Basic Policy on Conducting Phase I Trials in Japanese Patients Prior to the Start of Global Clinical Trials for Pharmaceuticals with Advanced Clinical Development Overseas" issued on December 25, 2023, but it was suggested that the safety of Japanese subjects may be the criteria for conducting Japanese PI trials. However, it was suggested that the safety of Japanese subjects may have been a criterion for the decision to conduct a Japanese PI study. The situation regarding rare disease and pediatric development remained the same as in previous years, and there was no difference in the ratio of development conducted in Europe, the U.S., and Japan. The presenters expressed their expectations for improvement of the development environment in the future, in light of the issuance of a notice to eliminate drug losses.
This presentation received the 14th Best Poster Award.
P-4 Yoshikazu Yamamoto (Japan Pharmaceutical Manufacturers Association, Regulatory Affairs Committee, Regulatory Affairs Subcommittee)
Questionnaire on the Status of Review of New Drugs 2024
Mr. Zenichi Yamamoto, a member of the Regulatory Affairs Committee of the JPMA, and others presented the results of a questionnaire survey conducted in January 2024 among 64 companies participating in the JPMA's Regulatory Affairs Committee with the purpose of evaluating the current status of the review process for new drugs approved in 2023 and suggesting efficiency and improvement measures. The results of a questionnaire survey conducted in January 2024 among 64 companies participating in the Pharmaceutical Affairs Committee of the Pharmaceutical Manufacturers Association of Japan (PMAJ) were presented.
The median time to approval for regular review items was 11.2 months, and 8.3 months for non-regular review items. 46% of the items were approved without an initial interview, an increase from 35% in the previous survey. The percentage of electronic data submission was 81%, up from 71% in the previous survey. In addition, there was a sharp increase in the number of respondents reporting insufficient time for reviewing examination reports. While the flexibility of the remote survey was appreciated, requests for improvement were raised, such as a lack of coordination in coordinating the survey schedule. There were also requests to reduce the burden of electronic application data and to ensure more time for checking the contents of the examination report. The committee expressed hope for further improvements in the examination process by streamlining the process, such as by making it fully electronic, improving the transparency of discussions at technical discussions, and reviewing the conformity survey.
P-21 Makoto Fujikawa (Japan Pharmaceutical Manufacturers Association, Regulatory Affairs Committee, Regulatory Affairs Subcommittee)
Expansion of the Standard Verification Certificate System and Further Streamlining of the GMP Conformity Assessment System - Consideration from the Standpoint of Manufacturers and Distributors
Mr. Makoto Fujikawa, a member of the Regulatory Affairs Committee of the JPMA, and others presented a paper on "Expansion of the Standard Verification Certificate System and Further Streamlining of the GMP Conformity Assessment System - Consideration from the Standpoint of Manufacturers and Distributors" under the theme of "Expansion of the Standard Verification Certificate System and Further Streamlining of the GMP Conformity Assessment System: Considerations from a Manufacturer's Standpoint. The results of a questionnaire survey conducted in November 2023 among member companies of the Regulatory Affairs Committee of the JPMA in November 2023 were compared with the results of the 2022 survey reported at the 2023 RS Conference. Since no progress has been made in the use of this system in the three years since its introduction, and no advantages of using this system can be seen from the standpoint of manufacturers and distributors, the next revision of the Pharmaceutical Affairs Law will expand the scope of application of the standard confirmation certificate (pre-approval/new drug first-time periodic/export GMP), streamline and improve the efficiency of GMP surveys, and in the future, it is expected that the system will be expanded to include the following In addition, he also expressed his belief that it is necessary to consider designing a system that can both increase the frequency of on-site inspections and strengthen GMP management at manufacturing sites, aiming for further risk-based GMP inspections on a manufacturing site-by-site basis in the future.
This presentation received the 14th Best Poster Award.
Concluding Remarks
The "Study Group on the Ideal Pharmaceutical Regulation System to Enhance Drug Discovery and Ensure Stable Supply" held in FY2023 discussed the resolution of the drug lag/drug loss problem, promotion of pediatric drug development, the ideal pharmaceutical affairs review process for drug manufacturing methods, and the ideal use of real-world data in the pharmaceutical affairs system. From 2024, the Pharmaceuticals and Medical Devices System Subcommittee has been discussing and examining the next revision of the system.
At the 2024 Annual Meeting, a symposium was held to discuss the contents of the study by the "Study Group on the Regulatory System for Pharmaceutical Affairs," and numerous active discussions were held from various perspectives. It is expected that the promotion of regulatory science and further cooperation between industry, academia, and government will be further promoted through these activities, and it is hoped that regulatory science will further develop and the activities of the society will become more and more active.
(Yutaka Takeuchi, Masayuki Taue, Kozue Shimizume, and Akinobu Nakanishi, Regulatory Affairs Committee)