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Until now, human bioequivalence (BE) studies were conducted based on the revised 'Guideline for Bioequivalence Studies of Generic Products' issued in 2012 by the Ministry of Health, Labour and Welfare (MHLW) in Japan. However, revisions of BE guidelines were required to account for the globalization of pharmaceutical development, new technology, and scientific rationales over the last 8 years. Therefore, the MHLW published the revised 'Guideline for Bioequivalence Studies of Generic Products' in 2020. In this article, we introduce the main revised contents, such as the addition of a fed-state BE study, reconsideration of the pilot study and add-on study, acceptance of foreign subjects in a BE study, and clarification of the requirement of a reference product. Furthermore, we compare the BE evaluations of generic oral solid dosage forms with those of the Pharmaceuticals and Medical Devices Agency (PMDA), the US Food and Drug Administration (FDA), and the European Medicines Agency (EMA).

The growth of healthcare cost is a serious issue in many countries. Generic drug products play an essential role in reducing healthcare costs because they are less costly than the innovator drug products. The regulatory review of generic drug products in Japan is conducted by the Pharmaceuticals and Medical Devices Agency (PMDA). This report introduces the activities of the PMDA from fiscal years 2014-2019. The number of approvals of new generic drug products and partial changes was trending downward. Alternatively, the PMDA conducted six types of consultation meetings to advise on development and application; the number of consultation meetings was increasing. Moreover, during this period, the Ministry of Health, Labour and Welfare issued two basic principles for ophthalmic dosage forms and dry powder inhaler drug products and revised the guidelines for bioequivalence. Finally, the future of generic drug product development and considerations to improve their regulation were discussed. More efforts will continue to enable a more efficient and rational generic drug product development and shortening of the review period for partial change approval.

In Japan, the revised version of bioequivalence (BE) evaluations for generic drug products was made available in 2012; however, the scope of this guideline is mainly oral solid dosage forms. Other dosage forms have to be discussed regarding how to evaluate BE by applicants and regulators during consultation meetings or the review process. Recently, there has been an increase in developing generic drug products in various dosage forms in Japan. Therefore, the Pharmaceuticals and Medical Devices Agency (PMDA) must strengthen their efforts to establish methodologies for BE evaluations for various dosage forms, including those of ophthalmic drugs. In 2016, the Japanese Ministry of Health, Labour and Welfare (MHLW) issued “The basic principles of bioequivalence evaluations of generic ophthalmic aqueous solutions.” This document presents recommendations for clinical endpoint BE studies or biowaiver options to evaluate the BE of generic ophthalmic aqueous solutions. However, this document has brought other issues to the forefront, such as the lack of feasibility of human BE studies for certain indications. Therefore, the PMDA, Japan Ophthalmic Pharmaceutical Manufacturer’s Association, and BE experts discussed these issues for 2 years, which led to an update by MHLW in 2018 entitled “The basic principles of bioequivalence evaluations of generic ophthalmic dosage forms.” This document describes methodologies for evaluating the BE of ophthalmic dosage forms including suspensions. This article introduces recently approved generic products of ophthalmic dosage forms in Japan, the basic principle of which was issued in 2018, and compares the BE evaluations between the PMDA and U.S. Food and Drug Administration.

All car of Tohoku-Shinkansen is equipped with the regeneration brake. This car is returning electric power to the Catenary line when it is braking. Regenerative power can improve the energy efficiency if other cars can use regenerative power. But the regenerative power flows back to the grid via the traction substation when other train does not exist in the same section. At this time, the regenerative power flowing back is not metered. This study is to measure the regenerative energy that flows back to the grid. We need determine the equipment capacity if installing the electric energy storage systems and the RPC for use up regenerative power. By using a linear programming, we determined the optimal capacity of the electric energy storage systems and the RPC.

In order to determine the deterioration of an arrester used in bullet train electricity feeding, it is effective to capture changes in the current of the resistance in the leakage current that flows through the grounding cable of the arrester. However, it is difficult to measure current of the resistance directly. In this research, we devised a principle for the detection of changes in current of the resistance by obtaining a leakage current that can be measured using the grounding cable of an arrester at an arbitrary date and time, and by calculating the difference with a reference leakage current. We have also developed a leakage current monitoring device for arrester by applying this principle to measure the current of the resistance at a bullet train substation.

In Japan, the development of generic oral dry powder inhaler (DPI) drug products for marketing approval has recently increased. The Pharmaceuticals and Medical Devices Agency (PMDA) considers the required data for each drug product in the consultation meeting. However, guidelines for DPI drug products have been published by the US Food and Drug Administration and the European Medicines Agency. Recently, the basic principles of bioequivalence evaluations of generic DPI drug products were published in March 2016 by the Ministry of Health, Labour and Welfare. The document mainly outlines the current understanding regarding the bioequivalence evaluations of generic DPI drug products based on knowledge from PMDA consultation meetings. In this review, we compared the bioequivalence evaluations of DPI drug products among Japan, USA, and the European Union and discuss future development of generic DPI drug products in Japan.

Masticatory muscle tone was investigated by analyzing vertical mandibular movement with electric stimulation. Healthy subjects and patients with type I TMD wereexamined. Under various conditions, masticatory muscle tone was evaluated by recording vertical dimension and velocity of mandibular movement.The results were as follows:1. Ten stimulations were applied with the mandible in the resting position. The descending dimension and maximum velocity of descent were measured.2. The mental anxiety of the subjects only slightly affected the mandibular movement with electric stimulation.3. Both parameters were lower in TMDpatients than in healthy subjects.4. Both of these values were lower before treatment for TMD than after treatment, and the values after treatment became similar to those in healthy subjects.

Purpose. A gap analysis survey of international practices for Active Substance Master Files (ASMFs)/Drug Master Files (DMFs) of human use was conducted as a project of the ASMF/DMF working group of the International Generic Drug Regulators Pilot (IGDRP) to identify similarities and differences among ASMF/DMF procedures of 10 IGDRP members and 2 observers. Methods. We conducted a questionnaire survey and compared the following aspects: overall ASMF/DMF procedures, submission requirements for ASMFs/DMFs, assessment processes for ASMFs/DMFs, the technical requirements for active pharmaceutical ingredients (APIs), generation of assessment reports for ASMFs/DMFs, procedures for changing ASMF/DMF details, and Good Manufacturing Practice (GMP) inspection/certification of API manufacturers. Twelve organizations participated in this project: the Brazilian Health Surveillance Agency (Anvisa), the European Union (EU), Health Canada (HC), the Singapore Health Sciences Authority (HSA), the South African Medicines Control Council (MCC), the South Korean Ministry of Food and Drug Safety (MFDS), the Japanese Pharmaceuticals and Medical Devices Agency (PMDA), the Swiss Agency for Therapeutic Products (Swissmedic), the Taiwan Food and Drug Administration (TFDA), the Australian Therapeutic Goods Administration (TGA), the European Directorate for the Quality of Medicines & HealthCare (EDQM) (Observer) and the Prequalification Team (PQT) of the World Health Organization (WHO), which includes the PQT–Medicines (Observer). Results. Although there were many similarities among the participating agencies surveyed, there were also differences that should be discussed such as assessment processes of ASMFs/DMFs and Technical requirements for APIs. Conclusions. These differences revealed by this survey will be key considerations in order to facilitate the filing of ASMFs/DMFs globally and to establish a framework for sharing and utilizing information related to ASMFs/DMFs among IGDRP members in the future. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

We have been developing an image processing method for the automatic inspection of electronic devices and implemented it on PC. And this system was already fabricated in the real production line for collecting the practical performance. 2D edge detection method for evaluating the surface recognition of the printed circuit board was proposed so far, and the validity was clarified. In this paper the outline of this system is firstly explained and the performance of this system is reported in detail. However, since some defects appear at the top surface of the mold cannot be detected even with a set of this 2D inspection procedure, new 3-dimensional inspection of the flatness of the mold top surface was introduced. Depth from Focus Method was implemented in order to enforce this system to cope with 3-dimensional defects. An image processing method for evaluating the flatness of the face of the device is now developed by analyzing this 3D image. Affine transformation is employed here to reduce the geometric distortions inherent in the given images.

Little is known about physiology and morphology of motoneurons and spindle afferents innervating the temporalis and on synaptic connections made between the two. The present study was aimed at investigating the above issues at the light microscopic level by using the intracellular recording and horseradish peroxidase or biotinamide labeling techniques and by the use of succinylcholine (SCh) for the classification of spindle afferents in the cat. Temporalis motoneurons had dendritic trees that ranged from a spherical form to an egg-shaped form. The shape deformation was more prominent for the dendritic trees made by motoneurons located closer to the nuclear border. No axon collaterals of the motoneurons were detected. On the basis of the values for the dynamic index after SCh infusion, temporalis spindle afferents were classified into two populations: presumptive groups Ia and II. The spindle afferents terminated mainly in the supratrigeminal nucleus (Vsup), region h, and the dorsolateral subdivision (Vmo.dl) of the trigeminal motor nucleus (Vmo). The proportion of group Ia afferent terminals was lower in the Vsup than that of group II afferents. In the Vmo.dl, the proportion of group Ia afferent terminals was nearly even throughout the nucleus, but that of group II afferent terminals increased in the more outlying regions. The proportion of terminal distribution in the central region of Vmo.dl was higher for group Ia than group II. The frequency of contacts (presumptive synapses) made by a single spindle afferent on a motoneuron was higher for group Ia than group II. The present study provided evidence that the central organization of spindle afferent neurons is different between groups Ia and II.

In an automatic loudness compensator provided in a sound reproduction device in a vehicle, the sound level is compensated to reproduce a sound source with the high fidelity intended by the producer of the source of sound. The level of sound frequency-pressure is increased or decreased relative to a middle range of sound frequency at a sound level lower or higher than a reference sound level, respectively. The level of sound frequency-pressure is also adjusted based on the noise produced by the movement of the vehicle and on the acoustic characteristic of the passenger compartment of the vehicle.

A vehicular speaker system in which a resonance of the vehicle's interior is compensated by a resonance of a chamber enclosing the rear of the speaker unit. The chamber includes rearwardly facing ports.

A car speaker system which can be used to radiate sound either inside the vehicle in normal driving use or outside the vehicle when the vehicle is parked. A plurality of speaker units are mounted in a closed cabinet and the cabinet is swingably mounted along one side thereof in a casing. In a first swinging position of the cabinet, the speaker mounting surface of the cabinet is flush with the ceiling panel and the speakers radiate sound downwards into the passenger compartment of the vehicle, while in a second swinging position of the cabinet, the speaker mounting surface is perpendicular to the ceiling panel and the speakers face rearwards to radiate sound to the exterior through an open hatchback door.

A method to improve finite element models for thermal deformation analyses has been proposed. In this method, a model is adjusted so that the results of analysis by the model fit experimental ones. The adjustment process consists of the following steps : first, a static deformation of a structure due to a unit force is obtained, based on Maxwell-Betti's reciprocal theorem, from the measured temperature distribution of the structure and the resulting thermal displacement measured at one point of the structure ; second, the experimental result thus obtained is compared with the analytical result obtained by static analysis by using the model ; third, the discrepancy between the two results is eliminated by modifying the analysis model. A case study has been done for a finite element model of an index unit of an NC lathe to show that this method is effective not only to improve the accuracy of finite element analysis but also to find out errors included in experimental data to be used in adjustment.