The development of pediatric drugs has long been recognized as a challenging endeavor internationally, primarily due to the small market size and the difficulties in conducting clinical trials. Additionally, there has been growing concern in Japan regarding the increasing drug loss of pediatric drugs in recent years. To address these challenges, the Ministry of Health, Labour and Welfare (MHLW) has been discussing on the direction of measures to promote such development, through a panel convened since 2023. Efforts have been made to enhance the regulatory environment, including the issuance of relevant notifications, to improve the current situation of pediatric drug development. The Clinical Evaluation Expert Committee of the Drug Evaluation Committee in Japan Pharmaceutical Manufacturers Association (JPMA) conducted an investigation on pediatric drugs approved from April 2018 to March 2023 in Japan aiming to help the planning and formulation of Pediatric Drug Development strategies and market authorization filings in Japan. As a result, the number of approved pediatric drugs showed an increasing trend during the investigation period. However, when compared to approval timing of the drug in Europe and the United States (US), approximately 30-40％ of approvals experienced a lag of over one year. The composition of clinical data-packages and approval lag between Japan and overseas was also compared. In clinical data-packages consisting of domestic clinical trials, 54.8％ were approved only in Japan, and 41.9％ had approval lag more than one year after approval in Europe or the US, indicating a polarization. In contrast, in clinical data-packages consisting of Multi Regional Clinical Trials (MRCTs), 69.6％ had an approval lag less than one year. Based on this investigation, it is considered effective to participate in MRCTs in order to obtain approval for pediatric drugs in Japan without delay from the Europe and the US. Furthermore, it is deemed important to maximize the use of existing data and construct flexible data-packages for approval when formulating development plans in Japan.

 Plenty of challenges related to the industry structure, pricing system, and distribution of generic drugs exist as underlying causes for the recent unstable supply of pharmaceuticals, mainly generic drugs. Small-volume multiproduct manufacturing is among them, and its association with the recent active joint development of generic drugs has been pointed out. Also, so-called “authorized generics,” a sort of joint development, is suggested to have been encouraging excessive price competition in the generic market. This study reports the state of joint development of generic drugs in Japan. A survey of popular generic drugs recently approved and listed in the national health insurance revealed that 50％ or more companies participated in joint development groups for more than half of the active substances, and that for products belonging to a same joint development group, the price has been revised to different price ranges, suggesting adverse effects on distribution as well as intensified price competition due to the increased number of generic products with a same substance. Also, authorized generics have been marketed for more than one-third of the substances and dominated the generic market, which can stifle reasonable competition. Systems for stable supply of pharmaceuticals need to be established based on the selection of companies capable of supplying products in a sustained and stable manner and reasonable competition among generic products through the improved handlings of the joint development from multiple perspectives including the revision of drug pricing system.

 Continuing medical education (CME) for healthcare professionals in Japan has not been structured into a systematized framework, and it is mostly left to individual autonomy. While various stakeholders such as medical societies and pharmaceutical companies support continuing education from their respective standpoints, CME activities provided by pharmaceutical companies are being met with high demand and expectations from healthcare professionals and are considered to play a certain role in their continuing education. Meanwhile, these activities have several issues, including restrictions on information provision due to industry regulations, not matching the educational needs of healthcare professionals, and many of them being short, one-time lecture meetings. One of the new CME support measures for pharmaceutical companies to solve these issues is Independent Medical Education Grants (IME Grants) led by Medical Affairs. IME Grants is a grant program that enables pharmaceutical companies to support continuous medical education programs carried out entirely independent of the companies through funding, but it has been adopted by only a limited number of pharmaceutical companies. This article describes the operational process of IME Grants and presents the points to note when a pharmaceutical company introduces IME Grants. Through proper utilization of IME Grants by both healthcare professionals and pharmaceutical companies, implementation of continuous and effective education programs is expected.

 In recent years, nitrosamines, which are carcinogens, have been detected in some sartan drugs, ranitidine, nizatidine, metformin, etc., in Japan and overseas. The possibility that nitrosamines may be present even in drugs other than those in which nitrosamines have been detected cannot be denied, and it is important to reduce the risk of contamination as much as possible. Therefore, the Ministry of Health, Labour and Welfare notified the marketing authorization holders to conduct self-inspection of risks of contamination with nitrosamines. After that, questions and answers, smoothly facilitating the self-inspection, was revised and the Carcinogenic Potency Categorization Approach (CPCA) for N-nitrosamines, which was introduced overseas, was also introduced in Japan. Furthermore, the cases of nitrosamine contamination of drugs in Japan and overseas were collected and organized, and items that should be provided from a toxicological perspective, such as carcinogenic risk assessment based on the CPCA, were considered in the Health and Labour Sciences Special Research Grant. As a result, risk communication guidelines were formulated that coordinate the categorization of contents to be provided to medical worker and methods of cooperation with related organizations. Along with making the established guidance known, we considered how to it to organize thoughts so that the health impact assessment results of nitrosamines can be promptly provided to medical facilities, prepare for the occurrence of future cases. We will continue to plan and implement administrative measures that will lead to the resolution of the issue of nitrosamine contamination of pharmaceuticals.

 This article introduces issues of quantitative assessment of carcinogenicity without threshold and provides an overview of research on carcinogenic potency for known nitrosamines. In most cases of quantitative assessment of non-threshold carcinogenicity, low-dose extrapolation is performed based on animal study data and the ICH M7 guideline recommends using TD₅₀ or BMDL₁₀. These indices for carcinogenic potency require a detailed examination of the validity of carcinogenicity studies, bases of the index derivation, and a decision on the policy to use benchmark dose methods. Recently, we examined the biological validity of the CPCA proposed by EMA. As a result, for some known nitrosamines, there was a gap between the estimated AI by the CPCA and the 10⁻⁵ carcinogenic risk level derived from originally calculated BMDL₁₀. Investigating the cause of this result would provide basic data to improve the CPCA or the establishment of a new method for estimating carcinogenic potency in future research.

 Continuous manufacturing attracted attention as an innovative manufacturing technology contributing to the stable supply of pharmaceutical products, and development of an internationally harmonized guideline for the implementation of continuous manufacturing was desired. ICH adopted a topic on the continuous manufacturing of pharmaceuticals in 2018, and the Guidelines for Continuous Manufacturing of Drug Substances and Drug Products (Q13) came into effect in Japan in May 2023. The ICH Q13 guideline applies to both drug substances and drug products for synthetic drugs and therapeutic proteins, and it consists of the main text and annexes. The main text describes the basic concept and points to be noted in the implementation of continuous manufacturing. The annexes contain illustrative examples and considerations specific to certain modalities. This article provides an overview of the ICH Q13 guideline, referring to the background and basic concepts (eg. scientific approach and regulatory considerations) described in the ICH Q13 guideline.