Objective: To survey the basic educational courses on Regulatory Science (RS) for drug development required by the model core curriculum for pharmaceutical education. Methods: We collected the online syllabi of pharmaceutical schools for the year of 2017 in Japan and identified the course related to drug development. Survey items included basic course information (e. g. targeted student grades, the number of credits, course names, course classification, and lecturer) as well as information on the lecturer; whether the lecturer was a member of the RS committee at the council on pharmaceutical education. Results and Discussions: We found that all pharmaceutical schools offered drug development courses and 78.2% of them required it as a compulsory subject. Therefore, it is indicated that drug development education has been penetrated broadly in Japanese pharmaceutical schools and its importance has been well recognized. However, differences in the number of credits and courses among schools suggested that ranges and contents of the courses may vary. Furthermore, provided that private universities had significantly better results compared to public universities, private universities may offer a detailed educational course with more contents on drug development. Conclusion: RS has established its position in the Japanese pharmaceutical education. However, implementation of standardized curriculum to suppress variations in drug development education should be considered. Likewise, a further enhancement of basic RS education; notably in public universities, is needed.

Investigator-initiated clinical trials provide important knowledge and insights for rational use of approved drugs and off-label use. However, it is unclear whether those results have been utilized effectively through publication or reporting to the clinical trial registration database. In this article, we investigated publication and reporting of the results of investigator-initiated clinical trials conducted in Clinical Trials Core Hospitals in Japan. We selected interventional trials of malignant tumor registered in UMIN-CTR (Clinical Trial Registry) between April 2009 and March 2015, whose completion was registered by March 1st 2017. We calculated proportion of publication of trial results and registering the results on UMIN-CTR. We identified 142 interventional trials across 7 Clinical Trials Core Hospitals. Over all, the proportion of publication of clinical trials was 73.0% (103/141). The proportion of registering results on UMIN-CTR was 4.9% (7/142). We found that there were about 30% of all clinical trials that were not effectively used because the results were not published. Apparent variations also appeared between hospitals. It is essential to motivate investigators for understanding the necessity of publication. We also found that UMIN-CTR was poorly managed regarding to the trial results. As the newly enacted Clinical Trials Act mandates reporting of specified clinical trials to jRCT (Japan Registry of Clinical Trials), the proportion of reporting results and its utilization will be improved.

This study investigated the prescriptions in which generic substitutions were not allowed by prescribers. Among 945,668 prescriptions received by 2,667 community pharmacies which belonged to Nippon Pharmacy Association during any one week from July 2018 to August 2018, there were 103,378 prescriptions (10.93%) in which generic substitutions were not allowed. Regarding “the percentage of prescriptions in which generic substitutions were not allowed” (hereinafter “the value” ) in each responded pharmacy, “≦5% of all the prescriptions” was most popular in 46.38% of the responded pharmacies, followed by “0% of all the prescriptions” in 17.51% of them. Though the average of “the values” among the responded pharmacies was 10.22%, the median value was 2.74%. Thus, there was a big difference in “the values” among the responded pharmacies because “the value” was 2-3% in over the half of the responded pharmacies, whereas, there were some pharmacies where “the value” was large. In Kyusyu/Okinawa region, the median value was 0.70%, the smallest among all the regions, and “the value” was ≦5% in over 75% of the responded pharmacies. In Hokkaido region, the average was 12.9%, the largest among all the regions, and “the value” was ≦5% in only 61.5% of the responded pharmacies. The average values were different among regions and were over 10% in Hokkaido, Chubu, Kinki and Shikoku regions. Regarding the reasons for not performing generic substitutions for the prescriptions in which generic substitutions were allowed, “patients' preferences” are most indicated by 94.94% of the responded pharmacies. As the other reasons described by the responded pharmacies, “prescribers' verbal instructions” was indicated most. Whereas “the value” was very small among over the half of the pharmacies, the value was large in some of the pharmacies. Therefore, the policy focusing these pharmacies in which “the value” was large. Further study is needed to expand the survey on the pharmacies with variety of characteristics.

Good Clinical Practice (GCP) are guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. The Office of Non-clinical and Clinical Compliance of Pharmaceuticals and Medical Devices Agency (PMDA) engages in onsite GCP inspection and document-based GCP inspection. In Japan, these two types of inspections are important to ensure the integrity of raw data including medical records, examination slips, and patient journals for application materials. We examined the compliance of GCP using review reports of new drugs discussed at the Pharmaceutical Affairs and Food Sanitation Council between FY2013 and FY2017. There were four new drugs related to inappropriate cases at some study sites, and PMDA asked the applicants to withdraw these cases from the dossier (a frequency of less than 3%). The revised dossier was acceptable for PMDA evaluation. All clinical trial information should be recorded, handled, and stored in a way that allows accurate reporting, interpretation, and verification, but medical records of some study sites were not found for some clinical trials of three new drugs. However, for document-based GCP inspection, the frequency of Voluntary Action Indicated (VAI) for GCP increased to 12.7% in FY2017. We also studied the Bioresearch Monitoring by Center for Drug Evaluation and Research (CDER) between 2013 and 2017 in Japan and found two VAI investigators. The clinical trial environment in Japan is improving, but more effort is needed to increase reliability and data integrity.

A system for prescription drugs to OTC switch was revised in Japan in May 2015. As a result of this change, when apply for approval of ingredients published to be a proper switch from prescription drugs, it was decided to submit the results of the user test about the package inserts as reference materials in principle. The purpose of this study is to clarify the issues to conduct “Proposal guidance to determine the level of understanding of package inserts for pharmaceuticals requiring guidance” issued on January 21, 2016. This study was conducted on a trial basis according to the proposed guidance. We composed package inserts of fictional drugs containing the minimum information based on the instructions. We studied whether subjects can understand the package inserts by interview. As a result, it did not meet the criteria for the level of understanding. However, we concluded it was possible to conduct the test according to the proposed guidance by devising the issues clarified in this study.

In June 2017, instructions for package inserts of prescription drugs in Japan were revised, and they shall be applicable from April 1, 2019. This revision is aimed at eliminating duplicate descriptions and integrating some notes, etc., and making the package inserts easier to understand and use. In particular, the precaution categories for specific patient groups that require attention during administration have significantly changed. In the previous instructions, the cautions for specific patient groups were described separately in “Contraindications”, “Relative Contraindications”, ”Careful Administration”, “Geriatric Use”, “Use during Pregnancy, Delivery or Lactation” and “Pediatric Use”. These are newly described and summarized in the new section, “Precautions concerning Patients with Specific Backgrounds”. In this article, we have introduced the points for checking the package inserts based on the new instructions, including the background of this revision and the differences from the previous instructions.

The circumstances surrounding medical care have been drastically changed. These include the advancement of medicine, aging of society, and development of IT technology; hence, the Instructions for Package Inserts of Prescription Drugs were stipulated as presented in the Appendix to make the package inserts and other relevant matters easier to understand and use. Ministry of Health, Labour and Welfare gave a notice the “Instructions for Package Inserts of Prescription Drugs” (PSEHB Notification No.0608-1 dated June 8, 2017, Ministry of Health, Labour and Welfare[MHLW]). And Japan Hospital Pharmacist Association published the “Instructions 2018 for Interview forms of Prescription Drugs” , too. So I presented Points to consider for its operations that clinical pharmacists.

The Instructions for Package Inserts of Prescription Drugs were revised in June 2017 to make them easier for the healthcare professionals who actually use them to understand, and more helpful for explanation to patients. The revisions made included the elimination of duplicate descriptions in package inserts, which was identified as an issue to be addressed in the previous version, and the consolidation of precautions previously referred to in different sections of the package inserts. In addition, a change was made to the format with which package insert information was digitized. This report summarizes the changes made to the Instructions for Package Inserts of Prescription Drugs in their latest revision, and provides their current status and the challenges facing pharmaceutical companies in relation.

In the development of pharmaceuticals and medical devices, utilization of Real World Data has been progressing internationally. Under such circumstances, in Japan, various strategies have been provided, such as the establishment of the “Clinical Innovation Network” aimed for clinical development utilizing registries, issue and enforcement of the revised “Ministerial Ordinance on Good Post-marketing Study Practice for Drugs (GPSP Ordinance), and notification on reexamination applications utilizing the registry, etc. PMDA has also set up new consultation categories from April 2019, to advise appropriateness of development plan utilizing registry data and method of ensuring the data reliability of registry data for approval applications, regarding individual products. This article introduces these new consultation categories.