Compared to conventional drugs, biomedicines are generally more clinically beneficial, but are relatively expensive and their use may contribute to increase in health care costs. In Japan, despite expectation of widespread use of biosimilars, the switch from original biomedicines to biosimilars has been slower than that from low-molecular-weight drugs to their generics. This could be because physicians and pharmacists are not fully aware that the efficacy and safety of an original biomedicine and its biosimilar are equivalent. We, therefore, examined the bioequivalency of original granulocyte-colony stimulating factor (G-CSF) biomedicines (G-CSF originators hereafter) and G-CSF biosimilars by comparing the efficacy and safety of the G-CSF originator, Gran^® Syringe (Kyowa Hakko Kirin Co. Ltd., Japan), with a biosimilar, Filgrastim BS Injection Syringe “F” (Filgrastim BS hereafter, Fuji Pharma Co. Ltd., Japan), by using data collected over 3 years, starting in April 2012, at Mishuku Hospital. The economic effect of switching to Filgrastim BS was also examined. We compared both G-CSF preparations in terms of time-dependent change in leukocyte counts, incidence of febrile neutropenia, and abnormal laboratory values. Because the time to start the administration of G-CSF differed between the originator-treated and the Filgrastim BS-treated groups due to the revision of the Clinical Practice Guidelines for Cancer, and leukocyte count instead of neutrophil count was used as the parameter, their efficacy could not be simply compared. However, the results suggest that Filgrastim BS is equivalent to its originator in terms of efficacy and safety in this study. Further, the cost-saving effect of switching to Filgrastim BS accounted for 10% of the entire cost saved by switching to generics and biosimilars in 2014. Thus, we demonstrated that switching from G-CSF originators to Filgrastim BS was beneficial for maintaining clinical efficacy and safety and reducing costs for Mishuku Hospital.

A questionnaire survey addressed to pharmaceutical companies was conducted to collect information on the situation and issues concerning EPPV (Early Postmarketing Phase Vigilance), which was conducted recently in Japan. It was shown that EPPV is conducted for almost all new drugs (including the cases for which new indication was added to the existing drugs). The result was put into a report and fed back to the medical personnel as a brochure or via a website for many cases. Safety specifications in the Risk Management Plan or materials of information provision including the package insert were revised based on the information obtained in the EPPV for about 15% of the cases. It was not feasible to evaluate the effect of EPPV from the viewpoint of risk-minimization activity. A lot of companies expressed their opinions calling for flexibility in the scope of new drugs for which EPPV is needed as well as in the method and operation of EPPV. It is quite important to implement risk management focusing on the early postmarketing phase of new drugs, and at the same time, we need to consider the balance between the resources for companies/medical institutions to implement safety measures and the performance (improvement of drug safety) demonstrated by EPPV.

All the people involved in clinical trials should ask themselves a question whether every process or judgment is appropriate or not. We want to introduce the importance of the moral education on data and quality management with making process. 1) moral education on data; It is easy for any clinical trialists to expect that the data could provide answers to their research questions. However, excessive expectations may raise another type of issues. The consequence may be the spread of a factually inaccurate information to the society. Therefore, it’s important to think about the meaning of trials with “Why” and to build the moral on the data by education. 2) quality management in clinical trials; A perfect preparation is unlikely, because unexpected problems cannot be prevented. When something goes wrong, there must be an assignable cause. By getting rid of such a cause, the process would become more reliable. Carrying out these activities repeatedly would make your clinical trials more reliable.

Pharmaceuticals and Medical Devices Agency (PMDA) has succeeded in shortening the review period for medical products to the world’s top standard through its 1st and 2nd Mid-term Plan Periods (FY 2004 to 2013). PMDA has been highly evaluated internationally for this and other achievements, and now positioned to contribute more to the world. In order to respond to the domestic and global expectations, PMDA has developed and announced its strategic plan titled “PMDA International Strategic Plan 2015”. This Strategic Plan outlines the international activities that will be conducted in the period defined in the 3rd and 4th Mid-term Plans, ending in FY 2023, taking into consideration the changes in the regulatory environment, as well as the Regulatory Strategy Initiative set forth by the Ministry of Health, Labour and Welfare (MHLW) in June 2015. As the development, manufacture, and distribution of medical products are becoming increasingly globalized, PMDA must collaborate with foreign regulatory authorities and other related parties. PMDA will make strenuous efforts in its international activities along with conducting efficient and effective product reviews, implementing safety measures, and providing relief services. The key international actions set forth in the “PMDA International Strategic Plan 2015” are to establish the “Regulatory Science Center” for conducting first-in-the-world product reviews, etc., to launch the “Asian Training Center for Pharmaceuticals and Medical Devices Regulatory Affairs” to share PMDA’s accumulated knowledge and experience in product reviews, etc., with Asian and overseas regulatory authorities, and to cooperate with overseas regulatory authorities for expansion of harmonization activities and work-sharing.

Recently globalization is promptly advancing in medical product development and its vigilance area. To adapt such circumstance change, Pharmaceuticals and Medical Devices Agency (PMDA) established “PMDA International Strategic Plan 2015” in June, 2015. In the Plan, PMDA declared the establishment of two centers, Regulatory Science Center and Asia Training Center for Pharmaceuticals and Medical Devices Regulatory affairs. On the basis of the Strategic Plan, “Asia Training Center for Pharmaceuticals and Medical Devices Regulatory Affairs (PMDA-ATC)” was newly established within PMDA on 1 April, 2016. The purpose of the Training Center is to provide the training for foreign regulators, especially in Asia, in response to the demands made by them by making use of the accumulated knowledge and experiences of PMDA. The content of the training seminar will include basic lectures on information necessary to build regulatory capacity in each country/region, such as benefit/risk assessment of the medical products, pharmacovigilance/medical device vigilance, Good Manufacturing Practice (GMP) inspection and so on. Besides, the Center will provide the programs such as on-site mock inspection in cooperation with actual manufacturing facilities. PMDA will, through the Center, contribute to enhancement and mutual understanding of regulations, and strengthening of cooperation in Asia and other parts of the world.

Good Registration Management (GRM) is the concept to promote Good Review Practice (GRevP) by review authorities and Good Submission Practice (GSubP) by applicants cooperatively. The purpose of GRM is to enhance quality and efficiency of medical product registration process from application submission throughout review and approval. The GRM was taken up as one of the official topics for regulatory convergence by APEC RHSC in 2015, and its training program has been developed under the APEC Training Center of Excellence (CoE) model by collaborations among the stakeholders from regulatory authorities, industry and academia. Summary of GSubP activities, as an essential element of GRM, will be described together with overall plan of the GRM training program.

Along with the slogan of “Medical Products for Overseas” by the Japanese government, we, i. e. International Policy and Strategy Committee at the Japanese industry, i. e. JFMDA (The Japan Federation of Medical Devices Associations) has been working together with Japanese government, MHLW (Ministry of Health, Labor and Welfare) and PMDA (Pharmaceutical and Medical Devices Agency) to harmonize medical device regulations with foreign countries since 2013. One of the challenge for Japanese medical device manufacturers is product registration when expanding their businesses abroad. Product registration is required in most countries under their own medical device regulations. However many Japanese companies are SME. So they did not always have enough human resources to handle Regulatory Affairs (hereunder “RA”) issues in house and/or “know-how” of product registration with foreign governments. Therefore, we assumed that lowering the level of such challenge might help them to expand their businesses outside Japan. To overcome this challenge, we think that improvement of regulatory science is very helpful for us. Because efficient and reasonable RA management skills and techniques can contribute to authorities in other countries, that may not have enough knowledge and experiences of RA, to provide new medical devices to their patients in a timely fashion. Through exchange activities of authorities between Japan and other countries, if such countries exempt some/whole either documents and/or data for medical product registration consequently, that would be a great help to Japanese medical device companies.

Primary strategy for conducting clinical trials in Japan has been shifting from domestic trials to bridging, and then global clinical trials. While several domestic guidelines have been released in recent years to assist in initiating global clinical trials, this issue was adopted as an ICH topic (E17) in 2014, and a draft of guideline was released to the public in 2016 for public consultation. Although multi-regional clinical trials including Japan, EU and US are common, East-Asian clinical trials have been also performed since East-Asian populations are assumed to have very similar genetic and cultural backgrounds. However, possibility is not excluded that population differences in pharmacokinetics and drug responsiveness may exist even among East-Asians. As a part of agenda for Japan-Korea-China Director-General Meeting on Pharmaceutical Affairs, Japan has been heading studies on differences in pharmacokinetic and drug responsiveness among East-Asian populations. Pharmacokinetic studies of three drugs on Japanese, Korean, Han Chinese, and Caucasian populations revealed no differences when the subjects in each population were stratified by genetic polymorphisms and extrinsic factors such as food and drinking water were normalized. These results suggest the importance of genetic polymorphisms and extrinsic factors in planning pharmacokinetic studies. Besides, we compared allele frequencies of more than 50 functional genetic polymorphisms in East-Asian populations, and found that generally, large differences were not observed in drug metabolizing enzymes and transporters; however, frequency differences were seen in HLA alleles associated with severe adverse drug reactions. We hope that our post and future results will promote East-Asian clinical trials, which will accelerate the availability of new drugs in these populations.