The aim of the study was to explore the characteristics of supplemental new drug application (s-NDA) and market expansion re-pricing (MErP). For 433 new active substances to which marketing approval was granted from 2008 April to 2020 March, we collected review reports on the s-NDA through December 2020 from the website of the Pharmaceutical and Medical Devices Agency and reports of market expansion re-pricing from that of the Central Social Insurance Medical Council, Ministry of Health, Labour and Welfare. One-hundred and fifty-eight drugs (36.5%) of 433 drugs obtained sNDA approval. Of them, a total of 214 sNDA approval for extensions of indications (sNDA-i) were granted for 131 drugs. Fifty point and five percent (46 drugs) of anticancer drugs received sNDA-i approval, which was the most among therapeutic categories. A total number of sNDA-i approval per a drug was 0.87 for anticancer drugs, which was the most among therapeutic categories, too. As for the period from NDA to the first sNDA-i approval, the mean of 13.7±5.5 (mean±S. D., months) and the median of 11.0 months in gastrointestinal drugs were the shortest among therapeutic categories, followed by 23.5 months for biologics, 24.0 months for anticancer drugs and 24.5 months for the allergy drugs. Of 131 drugs with sNDA-i approval, a total of 27 MErP have been applied to 25 drugs. More MErP have been applied to central nervous system drugs, other drugs affecting metabolism, and anticancer drugs. A total number of sNDA-i approval per a drug was 2.2 for drugs with MErP and 1.5 for drugs without MErP.

Reprocessed single-use medical devices (R-SUDs) are single-use medical devices collected from hospitals by the manufacturer for reuse after cleaning, sterilization, and performance testing. Regulations for R-SUDs have been implemented in Japan and some foreign countries. The characteristics of R-SUDs include collection form medical institutions, quality-assured transportation, and disassembly, cleaning, and reassembly in registered manufacturing facilities. In addition, manufacture of R-SUDs have to monitor the changes in the original medical devices that were used as the materials for remanufacturing of the R-SUDs. And manufacture also have to monitor the occurrence of malfunctions or adverse events that occur during the use of the R-SUDs and the original medical devices. Based on these features of R-SUDs, regulations has been implemented in Japan. For the further promotion of R-SUDs in the future, it is necessary to discuss how to effectively/rationally utilize and operate R-SUDs while ensuring the quality and safety of medical care for patients.

Raw materials used in the remanufactured single-use devices (SUDs) are obtained from SUDs that have previously been used at medical facilities in Japan. Thus, the system for remanufactured SUDs relies on medical facilities collecting and providing used SUDs. Herein, I describe the collection of used SUDs from the perspective of an operating department manager at a medical facility, namely Osaka Rosai Hospital, where I was previously employed. We predicted how many and what type of devices would be used, and in which operating room, and then placed boxes for collection. The decision on where to place the boxes in the operating room was made by the nurses and other front-line staff who actually put the used SUDs into the boxes. We clarified the timing of when to put the used SUDs into the boxes in the rooms and also who was responsible for putting used SUDs into the boxes after operations were completed. The boxes placed for used SUDs could not be transported directly out of the hospital, so they were packed and loaded onto special trucks for transport. The most important thing to consider when implementing a similar system and process is to minimize the nurses’ workload and make the process as easy as possible to understand. The entire process design from collection to transport was also a challenge, as was informing and educating the nurses. In addition, as the collected used SUDs are not garbage but instead raw materials, it is necessary to make sure that the used SUDs are handled with care.

The reprocessing of single-use devices (SUDs) is that the manufacturers responsibility collects the SUDs which have been used at medical facilities, disassemble, clean, replace the parts, reassemble, and sterilize, and then made commercially available after confirming to be as safe and effective as the original SUDs. The Japanese Ministry of Health, Labor and Welfare (MHLW) announced the establishment of a new system for the reprocessing of SUDs on July 31, 2017, and issued a notice on the Pharmaceutical Affairs Law. The cleanliness for reprocessing SUDs is required to be equivalent to that of the relevant original medical devices. However, since international standards for cleanliness assessment of reprocessing SUDs had not been developed, existing guidelines for reusable medical devices are to be considered as a reference. This section describes the trends in Japan and international standards for the cleanliness assessment of reusable medical devices, as well as the evaluation methods for residual protein and residual endotoxin, which are major markers for cleanliness evaluation.

In July 2017, the legal regime for remanufactured single-use devices (SUDs) was established in Japan, allowing manufacturers to collect used SUDs from medical institutions, disassemble, clean, replace parts as necessary, reassemble, and sterilize, and make them commercially available as remanufactured SUDs (R-SUDs) after performance testing. In order to actually commercialize R-SUDs, approval is required for each product, and at present, four items have been approved by two companies. Used SUDs need to be collected and transported separately from infectious wastes. In this paper, we describe the knowledge gained through the collection of used SUDs, consultations with the Ministry of Health, Labor and Welfare and the Ministry of the Environment, and the activities of Japan R-SUD Association (JRSA), during we have been conducting to commercialize R-SUDs.

There are orphan drug designation systems in Japan, the United States (US) and Europe (EU), but differences in the criteria for the systems. In Japan, although the Japan Agency for Medical Research and Development (AMED) has initiated the support program for orphan drugs prior to designation since 2017, the program is mainly supported by the development expenses, and it is considered that the needs of companies which promote research and development (R & D) in the early stages of development are not always satisfactory. Therefore, the Regulatory Affairs Committee of the Japan Pharmaceutical Manufacturers Association (JPMA) has been requesting the regulatory authorities for the orphan drug designation system in order to create an environment that can further promote the development of orphan drugs in Japan. In addition, a questionnaire survey was conducted in 2020 on the points considered by industries to be problematic in the current operation of the orphan drug designation system. As a result, it was revealed that there were many cases that did not meet the requirements for designation because the efficacy/safety was not shown to be remarkably high in comparison to existing drugs/treatments at the time of consultation for designation and there were several cases that affected the development plans, such as decreasing the priority of development, delaying the development, and discontinuing the development itself because it was not designated. In addition, the timing of designation was later in Japan than in Europe and the United States, and many products were designated in the later stage of development or immediately before the application for approval. An improved system to promote early R & D with earlier and broader orphan drug designation is desirable.