Japan Pharmaceutical Manufacturers Association Research Articles

Abstract PO2-26-04: Nature and Trends of Pharmaceutical Payments to the Board Certified Breast Cancer Specialists in Japan between 2016 and 2019

Abstract Background The field of breast cancer care has experienced a rapid influx of new treatments, making it a potential focus for promotional activities by pharmaceutical companies. These financial relationships could turn into significant sources of conflict of interest within the healthcare sector, possibly leading to undue influence on breast cancer care. Despite the potential ramifications of these ties, there is a noticeable lack of understanding about the details of financial relationships between pharmaceutical companies and breast cancer specialists. The aim of this investigation was to understand the extent and distribution of financial relationships between pharmaceutical companies and breast cancer specialists, along with their trends over recent years in Japan. Methods Our study included all 1733 board-certified breast cancer specialists registered with the Japan Breast Cancer Society as of May 2021. We obtained data on the payments they received, along with the intended purpose of each payment, from 92 leading Japanese pharmaceutical companies between 2016 and 2019. This data was disclosed by the companies following the transparency guidelines set forth by the Japan Pharmaceutical Manufacturers Association. Firstly, we conducted a descriptive analysis of the extent and distribution of payments to specialists, including a calculation of the Gini index to illustrate the disparity of payments among these specialists. Secondly, we assessed the overall trends and individual-based payment patterns over a four-year period. Finally, we explored whether the introduction of new agents was associated with variations in payment values at the company level. Results In total, 64 companies made 11,774 payments, collectively amounting to 13,329,919 USD, with speaking fees comprising 81.4% of this total. Among the 1733 specialists, 1306 (75.4%) received at least one payment from these companies. The average payment per physician was 7,692 USD (with a standard deviation of 24,162), and the median payment was 2,044 USD (with an interquartile range from 798 to 5,207 USD). Among these specialists, 27 received payments of 100,000 USD or more. The Gini index was 0.99, indicating a significant disparity in payment distribution among the specialists. There was a rising trend in total payment values, from 2,883,954 USD in 2016, to 3,037,888 USD in 2017, 3,589,583 USD in 2018, and finally 3,820,041 USD in 2019. A notable increase in payment value occurred with Pfizer in 2018, following the launch of Palbociclib in December 2017. Similarly, Eli Lilly, which launched Abemaciclib in November 2018, also increased its payments to specialists from 2018 onward. Conclusion: The majority of board-certified specialists in Japan received payments from pharmaceutical companies between 2016 and 2019. However, these payments were concentrated among only a small fraction of the specialists. During the study period, the overall value of payments increased. This surge likely resulted from the launch of key drugs within the same class and with similar indications, specifically CDK4/6 inhibitors. Citation Format: Akihiko Ozaki, Kenji Gonda, Masahiro Wada, Hiroaki Saito, Erika Yamashita, Tetsuya Tanimoto. Nature and Trends of Pharmaceutical Payments to the Board Certified Breast Cancer Specialists in Japan between 2016 and 2019 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-26-04.

Financial Relationships Between Pharmaceutical Companies and Internal Medicine Societies

This cross-sectional study uses payment data publicly disclosed by pharmaceutical companies affiliated with the Japan Pharmaceutical Manufacturers Association to describe their financial relationships with the subspecialty societies of the Japanese Society of Internal Medicine.

Using eConsent to improve patient comprehension and solving issues for introduction, with special attention to the COVID-19 pandemic: A questionnaire survey by the Japan Pharmaceutical Manufacturers Association

The environment surrounding clinical trials is evolving rapidly with the advancement of digital transformation (DX). Especially during the COVID-19 pandemic, digital methods are effective in promoting multiregional clinical trials (MRCT). eConsent is an electronic tool for obtaining informed consent that is expected as a key solution to improve patient understanding. According to the report by Pietrzykowski et al., patient understanding in clinical trials is surprisingly low, and this is a significant ethical problem. Despite the current situation, the use of eConsent has not significantly progressed at least in Japan. This study aimed to identify the current issues for eConsent and consider measures to solve them. In January 2022, an online questionnaire survey was sent to 69 member companies of the Japan Pharmaceutical Manufacturers Association (JPMA), and 52 companies (75.4%) responded. Thirteen companies (25.0%) conducted a trial using eConsent. Among the 13 companies, 17 trials were conducted by 8 companies after the COVID-19 pandemic (summer 2020), compared to 8 trials by 5 companies before the pandemic. We found that the biggest obstacles to the spread of eConsent are the lack of awareness of eConsent use and the development of provisions for treating electronic files as source records in medical institutions. In conclusion, we need to encourage medical institutions to update provisions for handling electronic source documents and to notify them of the importance of eConsent. Thus, further promotion of eConsent is needed to increase patient understanding and enable more efficient clinical trials.

Financial conflicts of interest between pharmaceutical companies and executive board members of internal medicine subspecialty societies in Japan between 2016 and 2020.

Pharmaceutical companies make payments to physicians such as compensations for lecturing or consulting. Of particular, financial relationships between pharmaceutical companies and leaders of professional medical societies are concern in medical community. However, little was known about them in Japan. This study aimed to evaluate the magnitude and prevalence of personal payments to executive board members (EBMs)of 15 medical associations representing different subspecialties within the Japanese Society of Internal Medicine. All EBMs of 15 medical associations representing internal medicine subspecialties were collected from each association webpage. Payments to the EBMs were extracted from the pharmaceutical companies belonging to the Japan Pharmaceutical Manufacturers Association between 2016 and 2020. We performed descriptive analysis on the payment data. Of the 353 different EBMs identified, 350 (99.2%) received one or more personal payments from the pharmaceutical companies over the 5 years. 99.2% (350) and 97.2% (343) of all EBMs received personal payments 3 years before and in the year of their board membership. A total of $70,796,014 were made to the EBMs over the 5 years. The median 5-year combined personal payments per EBM was $150,849 (interquartile range [IQR]:$73,412-$282,456). EBMs who were chairman or vice chairman of executive board received significantly larger median personal payments than those who were not ($225,685 vs. $143,885, p = 0.01 in the U test). Among the 15 societies, there were 12 (80.0%) societies with all (100%) EBMs receiving personal payments from the pharmaceutical companies. Although every society has their own conflicts of interest policy, none publicly discloses the financial relationships between pharmaceutical companies and their EBMs due to their privacy. This study demonstrated that nearly all EBMs of 15 medical associations representing internal medicine subspecialties had substantial financial relationships with the pharmaceutical companies in Japan over the past 5 years.

Changes in Japanese physicians' relationships with the pharmaceutical industry between 2008 and 2021: A national survey.

A national survey we conducted in 2008 showed that many Japanese physicians interacted with and received gifts from pharmaceutical representatives (PRs) and had a positive attitude toward relationships with PRs. The revised promotion code of the Japan Pharmaceutical Manufacturers Association in 2019 prohibited the provision of non-educational promotional aids including sticky notes, mouse pads, and calendars. During the COVID-19 pandemic in 2020, face-to-face meetings were socially restricted. This study assessed the extent of current Japanese physicians' involvement in pharmaceutical promotional activities and their attitudes toward relationships with PRs and to ascertain any changes between 2008 and 2021. We also examined the factors that predicted positive attitudes toward gifts from PRs. From January to March 2021, we conducted a national mail survey of Japanese physicians in seven specialties: internal medicine, surgery, orthopedics, pediatrics, obstetrics-gynecology, psychiatry, and ophthalmology. There were 1636 participants and the response rate was 63.2%. Most physicians met face-to-face with PRs (78.8%), whereas only a minority received meals outside the workplace (4.5%). PRs were thought to have an important role in continuing medical education (66.1%) and to provide accurate information about new drugs (74.2%). Opinions were divided on the appropriateness of gifts from PRs. Most thought that stationery and meals provided by the industry did not affect prescribing behavior (89.7% and 75.8%, respectively). Factors that predicted a positive attitude toward gifts from PRs were male, orthopedic specialty vs. internal medicine, more interactions with PRs, a positive attitude toward informational value, and no rules banning meetings with PRs. Involvement in pharmaceutical promotional activities is still common among practicing physicians in Japan, although the extent of the involvement had declined. Rules banning meetings with PRs appear to continue being effective at limiting a physician's involvement with promotional activities and their critical attitudes toward gifts from PRs.

Practice of Human Resource Development Related to Biopharmaceutical Manufacturing and Quality Control and the International Contribution as Centers of Excellence of Asia-Pacific Economic Cooperation-Life Sciences Innovation Forum-Regulatory Harmonization Steering Committee

In recent years, the development of biologics such as therapeutic antibodies has increased. Around 1980, Japan was the world's leading country in terms of research and development on biologics. However, after that, the development of biologics in Japan has become stagnant. Especially, research and development of therapeutic antibodies, which are critical medical products, is compared to that being conducted in Europe and the United States. The products distributed in Japan are developed and manufactured overseas. Furthermore, related emerging technologies are developed overseas. Therefore, to improve this situation, Biologics Center for Research and Training (BCRET) was established in August 2017 in Kobe city to develop human resources for biologics with the cooperation of Japan Pharmaceutical Manufacturers Association, Japan Agency for Medical Research and Development, Kobe University, and related ministries and agencies. BCRET will develop human resources by providing useful information and experience related to the development and manufacture of biologics in the form of classroom lectures and practical training for process and analysis developers and pharmaceutical affairs related to manufacturing, quality control, and approval applications in the biologics field of pharmaceutical companies, along with reviewers and inspectors of Pharmaceuticals and Medical Devices Agency and inspectors from countries belonging to Asia-Pacific Economic Cooperation (APEC). This is the first attempt in the world to develop human resources in a field of chemistry, manufacturing and control and Good Manufacturing Practice of biologics for inspectors in countries belonging to APEC, and it is expected to contribute internationally for human resources for biologics.

The Activities of the Continuous Manufacturing Project of Japan Pharmaceutical Manufacturers Association, Quality and Technology Committee

The Activities of the Continuous Manufacturing Project of Japan Pharmaceutical Manufacturers Association, Quality and Technology Committee

Bacterial mutagenicity test data: collection by the task force of the Japan pharmaceutical manufacturers association

BackgroundAmes test is used worldwide for detecting the bacterial mutagenicity of chemicals. In silico analyses of bacterial mutagenicity have recently gained acceptance by regulatory agencies; however, current in silico models for prediction remain to be improved. The Japan Pharmaceutical Manufacturers Association (JPMA) organized a task force in 2017 in which eight Japanese pharmaceutical companies had participated. The purpose of this task force was to disclose a piece of pharmaceutical companies’ proprietary Ames test data.ResultsAmes test data for 99 chemicals of various chemical classes were collected for disclosure in this study. These chemicals are related to the manufacturing process of pharmaceutical drugs, including reagents, synthetic intermediates, and drug substances. The structure-activity (mutagenicity) relationships are discussed in relation to structural alerts for each chemical class. In addition, in silico analyses of these chemicals were conducted using a knowledge-based model of Derek Nexus (Derek) and a statistics-based model (GT1_BMUT module) of CASE Ultra. To calculate the effectiveness of these models, 89 chemicals for Derek and 54 chemicals for CASE Ultra were selected; major exclusions were the salt form of four chemicals that were tested both in the salt and free forms for both models, and 35 chemicals called “known” positives or negatives for CASE Ultra. For Derek, the sensitivity, specificity, and accuracy were 65% (15/23), 71% (47/66), and 70% (62/89), respectively. The sensitivity, specificity, and accuracy were 50% (6/12), 60% (25/42), and 57% (31/54) for CASE Ultra, respectively. The ratio of overall disagreement between the CASE Ultra “known” positives/negatives and the actual test results was 11% (4/35). In this study, 19 out of 28 mutagens (68%) were detected with TA100 and/or TA98, and 9 out of 28 mutagens (32%) were detected with either TA1535, TA1537, WP2uvrA, or their combination.ConclusionThe Ames test data presented here will help avoid duplicated Ames testing in some cases, support duplicate testing in other cases, improve in silico models, and enhance our understanding of the mechanisms of mutagenesis.

Establishment and International Harmonization of Photosafety Testing Strategy

Considerable attention has been drawn to predict a photosafety hazard on new chemicals. A number of phototoxins tend to generate reactive oxygen species (ROS) via energy transfer mechanisms following UV/VIS excitation, including superoxide and singlet oxygen. Then, ROS assay has been designed to assess photoreactivity of pharmaceuticals, of which the principle is to monitor types I and II photochemical reactions of the test chemicals when exposed to simulated sunlight. This simple analytical test could be used to screen potential chemical scaffolds, leads, and candidate drugs to identify and/or select away from those having phototoxic potential. The validation study for the ROS assay has been being carried out by the Japan Pharmaceutical Manufacturers Association (JPMA), supervised by the Japanese Center for the Validation of Alternative Methods (JaCVAM). Although several false positives appeared, the ROS assay on 42 coded chemicals has provided no false negative predictions. The validation study tentatively indicates satisfactory outcomes in terms of transferability, intra- and inter-laboratory variability, and predictive capacity. Thus, a negative result in this ROS assay would indicate a very low probability of phototoxicity, whereas a positive result would be a flag for follow-up assessment. Upon international harmonization activities supported by several agencies and industrial groups, ROS assay was successfully adopted as International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) S10 guideline (2014) and Organisation for Economic Co-operation and Development (OECD) test guideline 495 (2019).

Consideration on Industry-Academia Partnering in Drug Discovery Development: Based on a Questionnaire Survey of Pharmaceutical Companies and Academia

Japanese pharmaceutical products continue to experience a trade deficit, since import values exceed export values. In drug discovery development, given the pace of technological innovations, there has been a major shift from low-molecular-weight compounds to biomedicine. It is anticipated that industry, academia and government will work more closely together in support of the pharmaceutical industry. Drug discovery requires much time and vast resources before the results can be put to practical use, and evidence suggests that many newly approved drugs derive from university-sourced technology. Pharmaceutical companies keep a close eye on technology evolving in universities. However, some reports state that there is a substantial difference compared to the development costs of the major Japanese pharmaceutical companies. Therefore, the authors hypothesized that there may be some issues hindering industrial-academic partnerships in drug discovery. In order to understand the actual situation and barriers to promoting industrial-academic collaboration, the Japan Pharmaceutical Manufacturers Association (JPMA), Japan Agency for Medical Research and Development (AMED), and the Medical Industry-Academia Collaboration Network (medU-net) Council will work together in issuing questionnaires and conducting an awareness survey. This survey sought the personal opinions of individuals belonging to JPMA and medU-net. Based on the results of this survey, we will introduce the issues related to industrial-academic collaboration and partnerships, and any gaps between industry and academia. Furthermore, we suggest solutions to promoting drug discovery innovation in Japan.

Qualitative analysis of actual Standard for Exchange of Nonclinical Data (SEND) datasets for Data Domains: Proposition from Japan Pharmaceutical Manufacturers Association SEND Taskforce Team on standardization of nonclinical data

The Standard for Exchange of Nonclinical Data (SEND) has been adopted by the US FDA, which has required pharmaceutical companies who are developing new drugs for the US market to implement SEND. The Japan Pharmaceutical Manufacturers Association (JPMA) SEND Taskforce Team responded to this situation by starting a project to better understand the contents of SEND datasets. The project focused on domains generally included in the SEND domains for single- and repeat-dose general toxicology studies, and surveyed what kind of information are populated in which domains and in what way. The qualitative analysis of the results indicated that variations exist based on whether or not an individual variable was populated and on how the variable was populated. The Taskforce Team recommends reducing variations not only in the SEND datasets but also in the descriptions in the study protocol and/or final study report. Reduction of such variations should lead to higher quality datasets with powerful and increased searchability so that accumulated SEND datasets should become more valuable. These efforts would provide regulatory agencies with easier review of SEND datasets, which contributes to efficient development of new drug candidates.

Comprehensive Cardiac Safety Assessment using hiPS-cardiomyocytes (Consortium for Safety Assessment using Human iPS Cells: CSAHi).

Current cardiac safety assessment platforms (in vitro hERG-centric, APD, and/or in vivo animal QT assays) are not fully predictive of drug-induced Torsades de Pointes (TdP) and do not address other mechanism-based arrhythmia, including ventricular tachycardia or ventricular fibrillation, or cardiac safety liabilities such as contractile and structural cardiotoxicity which are another growing safety concerns. We organized the Consortium for Safety Assessment using Human iPS cells (CSAHi; http://csahi.org/en/) in 2013, based on the Japan Pharmaceutical Manufacturers Association (JPMA), to verify the application of human iPS/ES cell-derived cardiomyocytes for drug safety evaluation. The CSAHi HEART team focused on comprehensive screening strategies to predict a diverse range of cardiotoxicities using recently introduced platforms such as the Multi-Electrode Array (MEA), cellular impedance, Motion Field Imaging (MFI), and optical imaging of Ca transient to identify strengths and weaknesses of each platform. Our study showed that hiPS-CMs used in these platforms could detect pharmacological responses that were more relevant to humans compared to existing hERG, APD, or Langendorff (MAPD/contraction) assays. Further, MEA and other methods such as impedance, MFI, and Ca transient assays provided paradigm changes of platforms for predicting drug-induced QT risk and/or arrhythmia or contractile dysfunctions. In contrast, since discordances such as overestimation (false positive) of arrhythmogenicity, oversight, or opposite conclusions in positive inotropic and negative chronotropic activities to some compounds were also confirmed, possibly due to their functional immaturity of hiPS-CMs, hiPS-CMs should be used in these platforms for cardiac safety assessment based upon their advantages and disadvantages.

Approach to Neurotoxicity using Human iPSC Neurons: Consortium for Safety Assessment using Human iPS Cells.

Neurotoxicity, as well as cardiotoxicity and hepatotoxicity, resulting from administration of a test article is considered a major adverse effect both pre-clinically and clinically. Among the different types of neurotoxicity occurring during the drug development process, seizure is one of the most serious one. Seizure occurrence is usually assessed using in vivo animal models, the Functional Observational Battery, the Irwin test or electroencephalograms. In in vitro studies, a number of assessments can be performed using animal organs/cells. Interestingly, recent developments in stem cell biology, especially the development of Human-Induced Pluripotent Stem (iPS) cells, are enabling the assessment of neurotoxicity in human iPS cell-derived neurons. Further, a Multi-Electrode Array (MEA) using rodent neurons is a useful tool for identifying seizure-inducing compounds. The Consortium for Safety Assessment using Human iPS Cells (CSAHi; http://csahi.org/en/) was established in 2013 by the Japan Pharmaceutical Manufacturers Association (JPMA) to verify the application of human iPS cell-derived neuronal cells to drug safety evaluation. The Neuro Team of CSAHi has been attempting to evaluate the seizure risk of compounds using the MEA platform. Here, we review the current status of neurotoxicity and recent work, including problems related to the use of the MEA assay with human iPS neuronal cell-derived neurons, and future developments.

Overview and transparency of non-research payments to healthcare organizations and healthcare professionals from pharmaceutical companies in Japan: Analysis of payment data in 2016

ObjectiveTo provide an overview of non-research pharmaceutical payments to healthcare organizations and professionals in Japan and evaluate data disclosure methods. MethodsWe calculated the aggregated value of each category of non-research payments among all 71 Japanese pharmaceutical companies belonging to the Japan Pharmaceutical Manufacturers Association. Non-research payments were categorized into academic research support expenses (e.g. donations), lecture, manuscript/writing, and consulting/commissioning fees, information provision-related expenses, and other expenses. Data disclosure methods for academic research support and lecturing/writing/consulting fees were evaluated through 11 factors, such as availability of individual payment data, disclosure of characters and figures with machine encoding, and possibility of data download as digital files. ResultsThe total value of non-research payments was US$1 762 119 513, with information provision-related expenses accounting for the largest proportion (US$1 138 049 361, 64.6 %). One company did not disclose individual payment data for academic research support and lecturing/writing/consulting and 31 (44.3%) of the remaining 70 demanded a registration for data access. Of the 70 companies disclosing data, 29 (41.4 %) disclosed characters and figures without machine encoding, and only 27 (38.6 %) allowed data download. ConclusionsJapanese healthcare organizations and professionals received significant amounts of non-research payments from pharmaceutical companies. Data disclosure methods did not provide adequate levels of transparency in these financial relationships.

Multiplicity Adjustment and Sample Size Calculation in Clinical Trials with Multiple Endpoints: An Industry Survey of Current Practices in Japan.

Two issues in clinical trials with multiple endpoints were surveyed: (1) the terminology of multiple endpoints, the relationship between rare events and endpoints, and the differences in multiplicity adjustment between regions, and (2) the current practice on multiplicity adjustment and sample size calculation. This article summarizes the results of the survey on the second issue. Eligible trials for this survey fulfilled the following conditions: (1) confirmatory phase 3 trial; (2) use of multiple primary endpoints, co-primary endpoints, key secondary endpoint(s) or composite endpoint(s); (3) inclusion of Japanese participants; and (4) protocols created in 2010 or later. The survey was conducted at member companies of the Japan Pharmaceutical Manufacturers Association from October 2017 to November 2017. Useable responses were obtained from 78 trials in 13 companies based in Japan and 9 companies based in other countries. The Bonferroni procedure was mostly used in clinical trials with multiple primary endpoints, while multiple testing procedures that consider a hierarchy of endpoints or a structure of hypotheses were used in clinical trials with key secondary endpoint(s). In sample size calculation, we can consider the probability of study success, such as the probability of statistical significance in at least one comparison of primary endpoints; however, other probabilities were also considered. This survey reveals that multiplicity adjustment and the correlation of endpoints were not always considered in sample size calculation. In clinical trials with multiple endpoints, clinical importance was considered when determining multiple testing procedures. Challenges remain with the definition of power, the consideration of multiple testing procedures and the correlation between endpoints in sample size calculation.

Challenges on Multiple Endpoints in Clinical Trials: An Industry Survey in Japan

Two issues on clinical trials with multiple endpoints were surveyed: (1) the terminology of multiple endpoints, relationship between rare events and endpoints, and differences in multiplicity adjustment between regions; and (2) the current practice on multiplicity adjustment and sample size calculation. This article provides a summary of the results of a survey on the first issue. The survey was conducted among 63 members of the Japan Pharmaceutical Manufacturers Association from October to November 2017. Thirty-five companies based in Japan and 12 companies based in other countries, 47 companies in total, responded to the survey. The terms co-primary endpoints, secondary endpoint, and composite endpoint were used in a variety of ways. An endpoint for a clinically most important event that is expected to occur rarely differed between regions. Although the Pharmaceuticals and Medical Devices Agency did not demand multiplicity adjustment, it was considered in clinical trials with multiple endpoints for approval in Japan. The use of terminology differed from the definition in the Food and Drug Administration guidance and the European Medicines Agency guideline. There remain challenges on a clinically most important event that is expected to occur rarely and multiplicity adjustment in clinical trials with multiple endpoints.

Current status of pathological image analysis technology in pharmaceutical companies: a questionnaire survey of the Japan Pharmaceutical Manufacturers Association.

The Japan Pharmaceutical Manufacturers Association (JPMA) has instituted a task force (TF) for the “development of image analysis technology for histopathological changes” as part of the collaboration for realizing cutting-edge drug development since 2016. In recent years, there has been progress in the digital pathology technology; however, few applications in nonclinical drug development studies have been observed. Therefore, TF performed a questionnaire survey to investigate the current status, needs, possibility, and development of image analysis. The subjects were 35 member companies of the JPMA. The questionnaire was set to assess the efficacy and/or safety of researchers engaged in pathological evaluations for each company. The questions focused on the experiences, implementation, and issues regarding histopathological examinations; the need for image analysis software; and future views. Valid responses were obtained from 26 companies. Most companies assumed that the beneficial aspect of image analysis is to gain objectivity and persuasiveness; however, challenges in the analysis conditions with regard to accuracy and without subjectivity persist. Additionally, there seems to be a need for image analysis software with advanced digital pathology technology, with most companies believing that, in the future, pathological evaluations will be partly performed by computers. In conclusion, in this questionnaire survey, TF extracted the current status of image analysis in nonclinical studies performed by pharmaceutical companies and collected opinions on future prospects regarding the development of image analysis software with advanced digital pathology technology.

Pharmaceutical payments to certified oncology specialists in Japan in 2016: a retrospective observational cross-sectional analysis

ObjectiveThis study investigated payments made by pharmaceutical companies to oncology specialists in Japan, what the payments were for and whether the receipt of such payments contravened any conflict of interest...

A Questionnaire Survey of Pharmaceutical Companies Affiliated with Japan Pharmaceutical Manufacturers Association on Current Use of Big Data/Real-World Data for Drug Development in Japan

A Questionnaire Survey of Pharmaceutical Companies Affiliated with Japan Pharmaceutical Manufacturers Association on Current Use of Big Data/Real-World Data for Drug Development in Japan

Development and application of Japanese kampo medicine granules

This article explores the development process of Japanese kampo medicine granules, which may be related to the popularization of convenience coffee in Japan in the 1940s. The development achievements were made mainly by two people: Itakura Takeshi and Watanabe Takeshi.Itakura Takeshi made the granule in 1944, and Watanabe Takeshi published an article about granule in 1947. In 1950, the granules were applied to clinic by Hosoya Shirou. In 1957, Kotaro pharmaceutical Co. Ltd was the first to sell granules in the market. Ten years later, in 1967, five classes and six kinds of drugs entered the Japanese medical insurance system, which has epoch-making significance in the history of the development of kampo medicine. Later, the guidelines of application and management for granules-The Handbook of Kampo Medicine Prescriptions for General Use-were formulated by experts convened by the Ministry of Health and Welfare of Japan, it had a great influence on clinical application. At the same time, Japan Pharmaceutical Manufacturers Association played a good coordinating role in the process of drug production and marketing.