Famous hypoglycemic drugs have found strong carcinogens.

Author:Kenji Bureau Time:2022.08.11

On August 9, the FDA released a message through the official website: the samples of Saglene Saginetine were detected by the sample of Nitramamines: Nitroso-STG-19 (NTTP).

Sigerine is a drug under the treatment of Type 2 diabetes under Merida. Based on Sigerine, Meroson has also developed a combination product of Sigerine and hydrochloride hydrochloride. In the past three years, these two drugs have brought more than $ 16 billion in revenue to Meridon.

Nitamines are a type of chemical carcinogen. In 2013, Huang Yang, a graduate student of Shanghai Fudan University School of Medicine, was poisoned by his roommate, and the poison was nitrosamine. According to the charges of prosecutors at the time, the criminal poisoning used at least 30 ml of second metrophic nitrosamine, exceeding 10 times more than 10 times the death.

In all animal experiments performed by nitrosamine, no animal can tolerate nitrosamine and do not have cancer. Therefore, the food industry has always been zero tolerance.

In 2018, due to the detection of N-Second-based nitrosamines (NDMA) impurities in the Saltan ingredients, the domestic ingredient giant Huahai Pharmaceutical was prohibited from exports by the FDA order, and the exports in the EU, Japan and other places were also restricted. As a result, Huahai's profit fell to the bottom. On August 11, Huahai Pharmaceutical told Jianxi Bureau: So far the lawsuit has not been finished.

However, this time, the nitrosamines were detected by Merck's hypoglycemic drugs, but the attitude adopted by the FDA was a lot mild. The solution given is: Sigerine can continue to use it, but you need to pay attention to the amount.

This way of treating is obvious.

Merrodida drug contains nitrine: pay attention to dosage

The FDA's disclosure of Sigerine mainly refers to Merck's patented medicine "Genoow", but it will also affect its same series of products.

"Genowei" is the world's first oral DPP-4 inhibitor in the world. It was approved by the FDA in 2006 for the treatment of type 2 diabetes. The response of this drug is good. In 2007, the sales reached US $ 668 million, and the revenue of three years of listing easily exceeded the $ 1 billion mark.

Based on the market performance of "Janovow", in 2007, Meridodon developed the Sigerine Erjia Double Two "Genoida", which was also launched. The China State Drug Administration approved the "Genowei" to be listed in China in March 2010.

Globally, "Jannov" is the main revenue of this series of Sigerine drugs. According to Merck's 2021 annual report, the global sales of "Jenovow" in 2019, 2020 and 2021 were US $ 3.482 billion, US $ 3.306 billion, and US $ 3.324 billion, respectively. In the past three years, the total revenue of "Genowei" and "Jonota" reached 16.088 billion US dollars.

For Sigerine's topic of carcinogens, the FDA is also a taboo device. The drug has a large demand in the US market. The FDA stated that it was worried that the patient's life would affect the patient's life due to the sudden shortage of drugs. It can only be recommended that doctors continue to use related drugs in the clinic, but the amount needs to be controlled.

In fact, the sales of the Sigerine series of drugs have fallen. In the first half of this year, Merck's "Jenoow" sales reached 1.535 billion US dollars, a decrease of 2%year -on -year; and sales of "Jonota" also decreased by 4%. This is because Sigerine is facing a patent cliff.

Meridodon disclosed in the 2022 interim report that two Sigerine drugs in the United States' market exclusive operating rights in the United States as of January 2023. Meridon is actively promoting the "salt/polycrystalline patent" of related products. If it is smooth, patent can be extended to 2027.

In China, in July 2022, the patent of the compound of this drug expired, and all patents expired until 2024. Pharma ONE database data shows that in 2021, the sales of the Chinese market in the Chinese market reached 3.4 billion yuan.

At present, companies such as Coron Pharmaceutical, Stone Medicine, Zhengda Tianqing, Gan Li Pharmaceutical and other companies have approved the Phosphates of Phosphate. One of the companies told the Jianxian Bureau: limited by patents, and now the products cannot be sold. It was also the earliest to be listed in 2024.

Huahai Lazartan incident: suppressed by FDA

Meridon's drugs found nitrosamine impurities and were not immediately removed from the shelves, which is much better than China's Huahai Pharmaceutical's fate.

In June 2018, Prinston Pharmaceutical Company, an American product manufacturer in the United States, pointed out to the FDA that a chemical named N-nitrotide (NDMA) provided by Huahai Pharmaceuticals found.

In July 2018, Huahai Pharmaceutical issued an announcement, acknowledging that there was indeed NDMA in the Sagazy Materials, and the "content was extremely small". At the same time, Huahai clearly stated that the relevant raw medicines were strictly produced in accordance with the GMP standards and registered regulations of each country. The two indicators of the unknown impurities and the total unknown impurities content of this raw material have always met the standards of ICH. "

It contained nitrosamine in medicines, and it was still an emergency at that time. Registration regulations of various countries did not clearly define the impurities due to the production process.

At that time, Huahai Pharmaceutical was the main supplier of Sagastean in the world. After the Nitamines incident occurred, the United States, the European Union, Japan and other regions opened a strict investigation of Sagastean. Another wave of land was recalled.

The FDA's blow is the strictest. In September 2018, the FDA announced that the export of preparation products made from all the raw medicines and raw materials produced by Huahai Pharmaceutical Southern Sichuan production base was exported to the United States. Subsequently, the Italian and European Drug Administration officially announced that Huahai Pharmaceutical Pharmaceutical Pharmaceuticals and the intermediate supply to the European market were prohibited. At the same time, American consumers began to filed a lawsuit against Huahai Pharmaceutical in court. For a while, Huahai Pharmaceutical became the target of public criticism, and the company's performance was also seriously affected: since 2015, the net profit of Huahai Pharmaceutical has not been less than 400 million, and in 2017, it reached 624 million yuan. However, in 2018, in 2018, in 2018, in 2018, in 2018, The net profit dropped to 135 million yuan.

The State Drug Administration also quickly took a response, issued an announcement requesting that five pharmaceutical companies including Chongqing Kangjie Pharmaceutical Co., Ltd. stopped using Huahai Pharmaceutical Pharmaceuticals Phantal Salone, and they must recall related drugs in accordance with regulations.

In May 2020, the State Drug Administration issued a notice from the "Research Technology Research Technology Research Technology Research Technology of Nitro Mamines in Chemical Drugs until the principle (trial)" to further control the safety and quality of drugs. The direct cause is the Huahai incident.

In December 2019, the exports of Huahai Pharmaceuticals in the EU were restored; in November 2021, Huahai Pharmaceutical announced that it received a letter of removal letter from the FDA's import ban from Huahai Pharmaceutical Southern Sichuan -Pharmaceutical Production Base.

The termination of the ban does not mean that the Sagazy incident ended, and Huahai Pharmaceutical's lawsuits in the United States are still underway. The 2021 annual report of Chunghwa Pharmaceutical stated that due to international arbitration, lawyers believe that the processing of the case may take two to three years.

Manufacturers should indeed pay for the fault. However, the difference between the FDA's different attitudes towards Sigerine and Pushadan raw material manufacturers is too obvious.

Writing ｜ Nicotinamide