Current status of development of anticancer agents in Japan

To investigate the current status of the development of anticancer agents in Japan, we examined the number of these agents developed after 1999, their target diseases, and the association between the number of approved agents and the number of patients with the diseases. The data were obtained via the Internet. Of the 487 agents approved from 1999 to April 2007, 84 were anticancer drugs. Of these 84, 46 were approved based on clinical trials and 38 were approved through the new drug application for off-label usages without clinical trials. The target diseases of the 46 agents approved through clinical trials were nonhematologic tumors in 29, hematologic malignancies in 13, and others in 4. Of the 38 approved through the new drug application for off-label usages, 31 were for nonhematologic tumors and 7 for hematologic malignancies. The number of approved anticancer agents for hematologic malignancies per unit patient population was 6.5-times as many as that for nonhematologic tumors. This study demonstrated that the situation regarding the development of anticancer agents differs among tumor types. The majority of anticancer agents developed target hematologic malignancies, while the newly developed anticancer agents have affected treatment strategies for solid tumors.     

Pharmacophore-based virtual screening: a review of recent applications

The global pharmaceutical industry is described as facing an ‘innovation crisis’ following the ‘go-go-pharma’ era; in other words, the problem is one of ‘more money and fewer products’. Nevertheless, patients worldwide are awaiting innovative drugs. Therefore, the pharmaceutical industry has a duty to discover and develop novel drugs and medical technologies. Through universal coverage and reform of the patent system, the Japanese pharmaceutical industry has expanded greatly in line with the Japanese economy. However, in terms of scale and R&D investment, the Japanese pharmaceutical firms have lagged behind the foreign multinationals, which have undergone successive mergers and acquisitions. Meanwhile, it is true that several Japanese firms are playing an active role in overseas markets with their own blockbusters. This paper analyses and gives an overview of new trends in Japan’s pharmaceutical industry within the global context.     

Going further than Lipinski's rule in drug design

Productivity in pharmaceutical R&D has been on the decline for the past several years, and much has been written on the subject. The causes for the decline in productivity are many and complex. Some of the causes are external to R&D and therefore difficult to address, such as growing regulatory conservatism and lack of international regulatory harmonisation. However, a number of the causes for the decline in productivity are internal to R&D groups and can be addressed by R&D managers, such as cost-containment and maximum use of resources. This article focuses on some of the major issues that have caused productivity to decline, and some of the areas where those who manage large R&D organisations may focus to improve R&D productivity.     

Therapeutic effect of bilastine in Japanese cedar pollinosis using an artificial exposure chamber (OHIO Chamber)

Background

Environmental exposure chambers have been used to expose subjects to aeroallergens to investigate the efficacy of prophylactic treatment with symptomatic agents in Japan. We first examined the therapeutic effect of bilastine (BIL), a novel non-sedative second-generation H₁-antihistamine, in subjects with Japanese cedar pollinosis using an artificial exposure chamber (OHIO Chamber).

Non-neoplastic lesions found only in the two-year bioassays but not in shorter toxicity studies of rats

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) has been conducting a prospective evaluation period to validate the criteria for waiving some carcinogenicity studies in rats. Before the waiving strategy is practiced in ICH, it is crucial to elucidate whether non-neoplastic lesions are found only in 2-year rat carcinogenicity studies. To confirm possible importance of 2-year bioassays for evaluating chronic toxicity but not carcinogenicity, we retrospectively surveyed 59 pharmaceuticals approved by the Ministry of Health, Labour and Welfare (MHLW) from 2007 to 2010 in Japan for non-neoplastic lesions observed in carcinogenicity studies. Non-neoplastic histopathological lesions observed only in 2-year carcinogenicity studies but not in 6-month chronic toxicity studies using rats were compared with clinical adverse drug reactions (ADRs). Thirteen non-neoplastic lesions that may correlate with clinical ADRs were classified into three categories: Category 1, lesions not predictable from other nonclinical data except those from 2-year rat carcinogenicity studies; Category 2, lesions predictable mainly from chronic toxicity studies; Category 3, lesions predictable mainly from pharmacological actions. In the present survey, non-neoplastic lesions only found in 2-year rat carcinogenicity studies were neither significant in terms of frequency and severity nor useful for clinical risk management.     

聚均苯四甲酸十二烷二醇酯的合成及表征

目的合成聚均苯四甲酸十二烷二醇酯,并对其进行表征。方法采用溶液缩聚法合成聚酯,单因素考察法优化工艺;红外光谱法和核磁共振氢谱进行表征。结果合成工艺为:溶剂原料比为2∶1,PMDA与DCD的摩尔比例为1∶1,催化剂为氯化亚锡,反应时间为10 h。红外光谱显示合成物结构中含有聚酯的基本官能集团和羧基,核磁氢谱显示生成了二元酯。结论成功合成了聚均苯四甲酸十二烷二醇酯。     

New Regulatory Framework for Medical Devices in Japan: Current Regulatory Considerations Regarding Clinical Studies

In Japan, a recent issue that required an urgent response was the streamlining of regulations concerning clinical trials of medical devices. On July 31, 2017, the Ministry of Health, Labour and Welfare enacted a new regulatory framework called the fast-break scheme for innovative medical devices aiming to expedite patient access while reducing the premarket regulatory burden of clinical trials and enhancing postmarketing commitments. The new framework is expected to provide greater benefits to patients who require access to new medical devices and to companies via improved transparency and predictability, as well as to reduce the social and medical cost incurred for medical innovation.