The European Medicines Agency (EMA) pointed out that "sartan-based drugs (antihypertensives) were contaminated with N-nitrosodimethylamine (ベラジョン ライブカジノ 表示名 変更) and N-nitrosodiethylamine (NDEA), which are of carcinogenic concern," causing a worldwide shock.
Concept
No Compromise inTechnological Innovation
Under this belief, we discovered through a thorough investigation process that one of the causes of nitrosoamine contamination, which poses a carcinogenic risk in pharmaceuticals, is trace amounts of nitrogen oxides (ベラジョン ライブカジノ 表示名 変更) in the air. To uphold the ideal "Towa Quality," we have successfully utilized science to achieve manufacturing in an unprecedented environment of 1 part per billion (ppb) level of ベラジョン ライブカジノ 表示名 変更, thereby controlling nitrosoamines. Our uncompromising challenge has no end.
Movement & Challenge Global Nitrosoamine Landscape and Our Challenge of Controlling ベラジョン ライブカジノ 表示名 変更
2018
2019
EMA released guidance to avoid the contamination of nitrosoamine impurities. "ベラジョン ライブカジノ 表示名 変更 was also detected in ranitidine (an acid suppressant)," leading pharmaceutical companies in Japan to conduct recalls. The Health Sciences Authority (HSA) of Singapore reported that "ベラジョン ライブカジノ 表示名 変更 was detected in metformin products (a diabetes treatment drug), and a voluntary recall of some affected products was initiated." The Food and Drug Administration (FDA) also began an investigation.
Towa Pharmaceutical also started an investigation into ベラジョン ライブカジノ 表示名 変更 contamination in metformin products.
2020
In the United States, NDMA contamination in ranitidine followed by nizatidine known as a gastric acid inhibitor and metformin products was reported; New ベラジョン ライブカジノ 表示名 変更 impurities findings have been extended to rifampicin and rifapentine, leading to industry-wide voluntary recall; FDA issued guidance for industry to perform nitrosoamine risk assessments in drugs.
We analysed total 881 batches of metformin tablets manufactured at two domestic plants (Osaka and Yamagata) and found that 1.9 % of total batches produced at Osaka plant exceeded the NDMA limit, prompting a voluntary recall; Since we hypothesised atmospheric ベラジョン ライブカジノ 表示名 変更-driven nitrosation should occur in batches above the limit, exhaustive investigation of environmental and manufacturing process conditions were initiated.
2021
With further expansion of the contamination of small-molecule ベラジョン ライブカジノ 表示名 変更 impurities represented by NDMA, the discovery of ベラジョン ライブカジノ 表示名 変更 drug substance-related impurities (NDSRIs = Nitrosoamine Drug Substance-Related Impurities) in which the drug substance itself has been nitrosated was recognized as a worldwide issue.The Ministry of Health, Labour and Welfare (MHLW) issued a Notice of Voluntary Inspection, requiring pharmaceutical companies to "conduct risk assessments (until April 30, 2023) " and "implement and report on risk mitigation measures (until October 31, 2024)".
We concluded that dimethylamine, which remained in trace amounts in the metformin drug substance, was likely to react with atmospheric ベラジョン ライブカジノ 表示名 変更 to form NDMA and led to contamination during the granulation process and reported to MHLW.We launched a cassette-screening analytical method covering nine regulated nitrosoamines so-called "Towa Amine Approach" to initiate a comprehensive nitrosoamines contamination risk assessment for all products.
2022
Guided by Prof. Norimichi Takenaka at Osaka Metropolitan University, we installed ベラジョン ライブカジノ 表示名 変更 monitors to measure atmospheric ベラジョン ライブカジノ 表示名 変更 concentration in TOWA Osaka plant, and demonstrated a clear correlation between AUC of atmospheric ベラジョン ライブカジノ 表示名 変更 concentration and NDMA contamination in the product.We achieved a world-first discovery by using model system to reveal that atmospheric ベラジョン ライブカジノ 表示名 変更 directly contributed to NDMA production during granulation/drying processes exposed to large amount of the air. Meanwhile, group company Daichikasei launched contract nitrosoamine analysis services.
2023
FDA issued its final guidance on acceptable daily intake for NDSRIs, while Japan's MHLW notified to extend the deadline for implementation of risk mitigation measures from October 31, 2024 to August 1, 2025.
We disclosed actual data and its analysis to the MHLW, reporting that atmospheric ベラジョン ライブカジノ 表示名 変更 is a key driver for nitrosation during manufacturing process, and published our findings in ACS Organic Process Research & Development. 1) The study—showing that even tens of ppb ベラジョン ライブカジノ 表示名 変更 can contribute to generating nitrosoamines—received an enthusiastic response from all over the world. At the same time, we started an unprecedented study to reduce atmospheric ベラジョン ライブカジノ 表示名 変更 to the ppb level (one part in a billion) during manufacturing process, aiming to completely suppress nitrosoamines in the products. 1) Shohei Fukuda, Kanako Kondo, Shoji Fukumoto,* Norimichi Takenaka, Osamu Uchikawa and Itsuro Yoshida：Organic Process Research & Development．2023；27(11)：2123-2133
2024
The FDA released its final guidance to control nitrosoamine impurities, along with recommendations for mitigation strategies on both small molecule ベラジョン ライブカジノ 表示名 変更 and NDSRIs.
We developed the ベラジョン ライブカジノ 表示名 変更 adsorption filter system to reduce atmospheric ベラジョン ライブカジノ 表示名 変更 to the ppb range, and the findings paved the way for plant-wide deployment. The article was posted in ACS Organic Process Research & Development.2) 2) Ryota Nomura*, Takahiko Taniguchi, Kazuya Suzuoki, Rintaro Yokoi, Kanenao Akasaki, Kyoko Hirai, and Osamu Uchikawa：Organic Process Research & Development．2025；29(1)：66-70
2025
We submitted a paper to ACS Organic Process Research & Development 3) describing the achievement of a nitroso-atomoxetine content of 0.097 ppm in a seamless pilot manufacture of atomoxetine under ベラジョン ライブカジノ 表示名 変更-free conditions by using a ベラジョン ライブカジノ 表示名 変更 adsorption filter system.Now we are ready to implement next generation ベラジョン ライブカジノ 表示名 変更 adsorption filters across production lines.3) Ryota Nomura*, Takahiko Taniguchi, Koji Kitada, Mamoru Otsuki, Takuma Tamai, Kazuya Suzuoki, Rintaro Yokoi, Kanako Kondo, and Osamu Uchikawa：Organic Process Research & Development．2025；29 (9)：2259–2264
R&D News
- Received the Medicinal Chemistry Symposium (MCS) Award at the 42nd Medicinal Chemistry Symposium hosted by the Division of Medicinal Chemistry, Pharmaceutical Society of Japan
- 2025 Academic Award for Division of Particulate Design and Preparations.The Offensive and Defensive Battle Against ベラジョン ライブカジノ 表示名 変更 —The Path from Investigation of cause to Implementation—
- Dr. Osamu Uchikawa made the seminar talk in the INTERPHEX Week Tokyo 2025
Interview
Aimingto Resolve Risks Associated with Pharmaceutical Components (Active Pharmaceutical Ingredients, Excipients)
Project Leader (Chemist)
Osamu UCHIKAWA, ベラジョン ライブカジノ 表示名 変更D.
Our Vision for “the ベラジョン ライブカジノ 表示名 変更 Think Tank”: Transcending Conventions to Forge the Future
Project Member (Engineer)
Hirokazu KISAKA
Our Aspiration to Contribute to the Pharmaceutical Industry at the Forefront of Trace Analysis
Project Member (Analytical Researcher)
Shohei FUKUDA, ベラジョン ライブカジノ 表示名 変更D.
Pioneeringthe Development of a World's First Filter from Scratch
Project Member (Chemist)
Ryota NOMURA
Our Strategy and Results
Pursuing the Essence
The team members full of expertise, curiosity, flexibility, judgment, and execution power never settle for the status quo, never give up, and tirelessly tackle problem-solving every day.
Developing Trace Analysis
Using high-performance, state-of-the-art analytical instruments, the team members are developing efficient analytical methods to rapidly and accurately measure "trace amounts of ベラジョン ライブカジノ 表示名 変更 contained in medicines," ensuring that products are delivered to the market without any blemishes.
Creation of ベラジョン ライブカジノ 表示名 変更 Removal System
We have developed the excellent ベラジョン ライブカジノ 表示名 変更 removal system by considering every possible measure and through trial and error to reduce ベラジョン ライブカジノ 表示名 変更 to a few ppb levels (akin to finding one person in a country with a population of one billion).
Refine APIs/DPs Manufacturing Process
Manufacturing methods, equipment, and environment for Active Pharmaceutical Ingredients (APIs) and Drug Products (DPs) are carefully reviewed one by one to reliably and proactively prevent the contamination of ベラジョン ライブカジノ 表示名 変更.
Refine Packaging Materials and Storage Methods
We select packaging materials that ensure no contamination with ベラジョン ライブカジノ 表示名 変更 can occur, confidently delivering safe and secure pharmaceuticals to the market.
