Beta Pharma Breaks Foreign Monopoly with Proprietary C-14 Labeled Key Intermediate Compounds
Public understanding of C-14 (carbon-14, a radioactive isotope of carbon) may still be largely confined to radiocarbon dating in archaeology. I recall that archaeological programs I frequently watched as a child often mentioned C-14 dating. In reality, beyond its application in archaeological dating, C-14 has been widely utilized in the fields of healthcare, agriculture, chemical engineering, and environmental protection.
However, for a long time, China has heavily relied on imports for carbon-14 (C-14) raw materials and intermediates, which has been highly detrimental to the development of its isotope technology and application industries. In Wuxi, Jiangsu Province, there is a company addressing this issue. Over nearly a decade, it has dedicated itself to researching and developing key C-14 intermediate compounds, aiming to break the foreign monopoly over the C-14 industrial chain through independent technological innovation, thereby enabling China to establish its own C-14 supply chain and labeled products. This company is Wuxi Beita Pharmatech Co., Ltd.
In the process of isotope-labeled synthesis, the key lies in the production of labeled intermediates. These labeled intermediates primarily serve as raw materials for the subsequent production of compounds, such as formic acid, acetic acid, benzoic acid, and cyanides. During the synthesis of isotope-labeled compounds, it is necessary to first replace carbon-12 (C-12) in these intermediate compounds with carbon-14 (C-14) through various chemical reactions. These C-14-labeled intermediates are then used to synthesize the final target compounds, thereby imparting the C-14 isotopic label to the end products.
Domestic isotope-labeled intermediates have long relied heavily on imports. The R&D team at Wuxi Beita Pharmatech Co., Ltd. has been painstakingly developing production technologies for these labeled intermediates, one by one, aiming to break the foreign monopoly on C-14 intermediates.
During this period, Wuxi Beita Pharmatech received substantial support from multiple national science and technology talent programs and funds, including the Wuxi “530” Talent Program, the Jiangyin City Science and Technology Support Program, the Jiangsu Province Science and Technology Support Program, and the Innovation Fund of the Ministry of Science and Technology. Living up to expectations, Wuxi Beita Pharmatech successfully synthesized dozens of commonly used key intermediate compounds. These technological breakthroughs have brought China’s production of C-14 isotope-labeled compounds one step closer to complete domestic self-sufficiency.
In medicine, the primary applications of C-14 are radioactive isotope tracing and the detection of Helicobacter pylori infection.
“The application of low-energy radioisotope-labeled compounds (such as C-14 and H-3) in pharmacokinetic studies has been proven to be a safe and effective specialized technique. Due to the very low background levels of these isotopes in biological systems, detection is easy and highly sensitive. Their long half-lives eliminate the need to correct test results for radioactive decay. They allow for quantitative analysis of metabolites generated from candidate drugs without requiring prior knowledge of their structures. Furthermore, the non-ionizing beta rays they emit have extremely low energy, obviating the need for special radiation protection. The results obtained are straightforward, clear, and reliable, and in most cases, there are currently no alternative methods available.” This description is not hearsay; it is excerpted from the Technical Guidelines for Non-Clinical Pharmacokinetic Studies of Drugs issued by the former State Food and Drug Administration.
Carbon-14 is used for radioactive isotope tracing, effectively equipping target molecules with a navigation system for precise localization and tracking. Compounds synthesized with Carbon-14 exhibit chemical properties nearly identical to those of their non-labeled counterparts. Radioactive isotope tracing offers three major advantages: high sensitivity, simple detection methods, and accurate qualitative and quantitative localization.
Radioactive tracer methods exhibit extremely high sensitivity, capable of detecting quantities at the level of 10⁻¹⁴ to 10⁻¹⁸ grams; that is, a single radioactive atom can be detected among 10¹⁵ non-radioactive atoms, making it even more sensitive than analytical balances. When used for in vivo tracing, radioactive measurements are not subject to interference from other non-radioactive substances, and results can be obtained through external measurements, offering great convenience. Furthermore, due to the extremely low natural abundance of radioactive isotopes, their detection is virtually unaffected by background factors, allowing for accurate localization and quantification.
Detection of Helicobacter pylori infection is more closely aligned with daily life. The C-13 or C-14 urea breath test system is currently recognized as the gold standard for detecting Helicobacter pylori. After the subject orally ingests a capsule, they exhale into a collection bag. The capsule contains urea molecules labeled with C-13 or C-14. If Helicobacter pylori is present in the stomach, the labeled urea molecules are broken down, producing CO2. Consequently, CO2 labeled with C-13 or C-14 can be detected in the gas collected in the exhalation bag.
Carbon-13 is one of the stable isotopes of carbon and occurs naturally. It is non-radioactive and accounts for approximately 1.11% of natural carbon. Therefore, raw materials containing Carbon-13 are primarily obtained through extraction from natural sources. The production of ¹³CO, a Carbon-13-based raw material, requires selection of geologically stable regions and distillation in fractionating columns up to 200 meters in height, making the manufacturing process extremely challenging.
Currently, the major global suppliers of C-13 raw materials are all located in the United States, with limited annual production. Even if the entire annual output of C-13 were dedicated to producing reagents for Helicobacter pylori detection, it would only meet the testing needs of approximately 20 million people per year. In comparison, the amount of C-14 required for testing is significantly smaller. One gram of C-14-labeled urea can satisfy the testing demands of nearly one million individuals. Furthermore, due to the minimal dosage used in testing, the radiological impact of C-14 on the human body is virtually negligible. Undergoing a breath test by ingesting one C-14 urea capsule exposes an individual to radiation equivalent to that from consuming ten bananas.
Therefore, only reliance on C-14 can meet the global demand for testing Helicobacter pylori infection.
Wuxi Beita Pharmatech Co., Ltd. currently operates a 2,400-square-meter dedicated laboratory building for C-14 and H-3 labeling in the Jiangyin High-Tech Zone of Wuxi. Additionally, the company maintains a 1,500-square-meter dedicated laboratory for C-13, N-15, and H-2 labeling in Changsha. Since its establishment, Wuxi Beita Pharmatech has obtained 16 invention patents and developed hundreds of isotopically labeled precursor compounds. In March 2019, Science and Technology Daily reported on the company’s achievements, with the article simultaneously published on the “Xuexi Qiangguo” platform.
In April 2014, Beita Pharmatech secured Series A financing from Shanghai Kaiwu Investment. In the first half of 2019, it completed another round of financing amounting to approximately RMB 10 million.
2018 was a significant year for Wuxi Beita Pharmatech Co., Ltd., which had been established for ten years. In early 2018, the company officially launched its C-14 isotope labeling services, establishing partnerships with leading domestic new drug developers such as Hansoh Pharmaceutical, Hengrui Medicine, Kelun Pharmaceutical, Nanjing Sanhome Pharmaceutical, Beijing Sailintai, and Fujian Haixi Pharmaceutical, and successfully achieved profitability.
In addition to its existing operations, Wuxi Beita Pharmatech Co., Ltd. is actively expanding its business scope. The company is currently planning the development of diagnostic kits for Helicobacter pylori, which will be sold directly to consumers in the future. Recently, documents issued by the Ministry of Ecology and Environment have brought new development opportunities to Wuxi Beita Pharmatech.
In January 2019, the Ministry of Ecology and Environment released the “Regulations on Environmental Impact Assessment and Control of Chemical Substances (Draft for Comments).” This draft primarily targets enterprises in China engaged in the production, processing, use, import, and export of chemical substances, requiring them to conduct environmental risk assessments, implement prevention and control measures, and comply with regulatory oversight for such substances.
As the world’s largest producer of chemicals, China is poised to unlock substantial market opportunities driven by tightening regulatory policies on chemical substances. The high sensitivity and precise localization capabilities of C-14 isotope labeling make it particularly well-suited for in-depth assessment of the environmental impacts of chemicals.
A bulletin from the United Nations Atomic Energy Agency stated, “In terms of the breadth of application, only modern electronics and information technology can be compared with isotopes; isotope technology is making valuable contributions to global socio-economic development.” For Beita Pharmatech, the past decade has been one of enduring hardships and forging ahead, achieving the transition of key C-14 intermediate compounds from import reliance to domestic production in China, thereby laying a solid foundation for future development.
The coming decade will be one of leveraging momentum to accelerate development. Although Wuxi Beita Pharmatech Co., Ltd. has already launched full-scale industrialization of C-14 and other isotope labeling and achieved profitability, it is far from time to rest on its laurels. In the next ten years, the company will continue to focus on deepening its expertise in isotope technology and its applications, enabling more isotope-labeled compounds and labeling services to replace imports with domestically produced alternatives, thereby harnessing isotope technology for the benefit of China and the world at large.
