Well-known hypoglycemic drugs found strong carcinogens, FDA "double standard" treatment of Chinese and American companies

On August 9, the FDA released a message on its official website: A sample of the hypoglycemic drug sitagliptin was detected to contain nitrosamine impurities: Nitroso-STG-19 (NTTP)

Sitagliptin is Merck's drug for the treatment of type 2 diabetes.

The two drugs have brought in more than $16 billion in revenue for Merck in three years

chemical carcinogens

In all animal experiments on nitrosamines, no animal can tolerate nitrosamines without cancer

No animal can tolerate nitrosamines without causing cancer

In 2018, due to the detection of N-dimethylnitrosamine (NDMA) impurities in the valsartan API, the domestic API giant Huahai Pharmaceutical was banned from export by the FDA, and its export in the European Union, Japan and other places was also restricted.

On August 11, Huahai Pharmaceutical announced that the lawsuit has not been completed so far

Sitagliptin can still be used, but need to pay attention to the dosage

In this way, the double standard is obvious

Merck Drugs Contain Nitrosamines: Pay Attention to the Dosage

Merck Drugs Contain Nitrosamines: Pay Attention to the Dosage

The FDA's disclosure of the problematic sitagliptin this time mainly refers to Merck's patented drug "Jenovi", but it will also have an impact on its same series of products

Mainly refers to Merck's patented drug "Jienovi"

"Jianowei" is the world's first approved oral DPP-4 inhibitor, which was approved by the FDA in 2006 for the treatment of type 2 diabetes

Based on the market performance of "Jenovi", in 2007, Merck developed the sitagliptin metformin "Jenoda", and subsequently launched a sustained-release dosage form

In March 2010, China's State Food and Drug Administration approved the listing of "Jenovi" in China

Regarding the topic of sitagliptin containing carcinogens, the FDA is also a rat-avoider

FDA expresses concern about impact on patients' lives due to sudden drug shortage

In fact, the sales of sitagliptin series drugs have been declining

That's because sitagliptin is facing a patent cliff

On the Chinese side, the compound patent of this drug will expire in July 2022, and all patents will expire in 2024

The compound patent of this drug will expire in July 2022, and all patents will expire in 2024

At present, domestic companies such as Kelun Pharmaceutical, CSPC, Chia Tai Tianqing, Ganli Pharmaceutical and other companies have been approved for the generic drug of sitagliptin phosphate

The product is not available for sale now
.
Listing not until 2024 at the earliest

Huahai valsartan incident: suppressed by FDA

Huahai valsartan incident: suppressed by FDA

Merck's drug found nitrosamine impurities and was not immediately removed from the shelves, which was much better than China's Huahai Pharmaceutical
.

In June 2018, Prinston Pharmaceuticals, a valsartan product manufacturer in the United States, pointed out to the FDA that a chemical called N-nitrosodimethylamine (NDMA) was found in the API provided by Huahai Pharmaceutical
.

A chemical called N-nitrosodimethylamine (NDMA) was found in the API provided by Huahai Pharmaceutical
.

In July 2018, Huahai Pharmaceutical issued an announcement acknowledging that NDMA does exist in the valsartan API, with "very little content"
.
At the same time, Huahai made it clear that the relevant APIs "are produced in strict accordance with the GMP standards and registration regulations of the countries where they are supplied, and the two indicators of the single unknown impurity content and the total unknown impurity content of the API have always met the ICH standards
.
"

Strictly comply with the GMP standards and registration regulations of the countries where the supply is located

The inclusion of nitrosamines in pharmaceuticals was still an emergency at that time, and the registration regulations of various countries did not have a clear standard definition for this impurity generated by the production process
.

Huahai Pharmaceutical was the main supplier of valsartan in the world at that time.
After the nitrosamine incident, the United States, the European Union, Japan and other regions all launched strict investigations on valsartan APIs, and Huahai Pharmaceutical has a wave of related products.
It was recalled again and again
.

Huahai Pharmaceutical was the main supplier of valsartan in the world at that time

The FDA has hit the hardest
.
In September 2018, the FDA announced that it would prohibit the export of all APIs and preparations made from APIs produced by Huahai Pharmaceutical's southern Sichuan production base to the United States
.
Subsequently, the official announcement of the Italian and European Medicines Agency stated that Huahai Pharmaceutical's valsartan raw materials and intermediates were prohibited from being supplied to the European market
.

Prohibits the export of all APIs and preparations made from APIs produced by Huahai Pharmaceutical's southern Sichuan production base to the United States

At the same time, U.
S.
consumers began to file lawsuits against Huahai in court
.
For a time, Huahai Pharmaceutical became the target of public criticism, and the company's performance was also seriously affected: since 2015, Huahai Pharmaceutical's net profit has not been less than 400 million yuan, and in 2017 it reached 624 million yuan; but in 2018, Net profit plummeted to 135 million yuan
.

In 2018, net profit dropped to 135 million yuan

The State Food and Drug Administration also responded quickly, issuing an announcement requiring 5 pharmaceutical companies including Chongqing Kangkeer Pharmaceutical Co.
, Ltd.
to stop using Huahai Pharmaceutical's valsartan API, and to recall related drugs according to regulations
.

In May 2020, the State Food and Drug Administration issued a notice on "Technology for Research on Nitrosamine Impurities in Chemical Drugs until Principles (Trial Implementation)" to further control the safety and quality of drugs.
The direct cause is the Huahai incident
.

The direct cause is the Huahai incident

In December 2019, Huahai Pharmaceutical's exports to the EU were resumed; in November 2021, Huahai Pharmaceutical announced that it had received the FDA's letter of lifting the import ban on Huahai Pharmaceutical's raw material drug production base in southern Sichuan
.

The lifting of the ban does not mean the end of the valsartan incident, and many lawsuits of Huahai Pharmaceutical in the United States are still ongoing
.
The 2021 annual report Zhonghuahai Pharmaceutical stated: Due to the involvement of international arbitration, lawyers believe that the procedural processing of this case may take two to three years
.

Huahai Pharmaceutical's many lawsuits in the United States are still in progress

Manufacturers should indeed pay for their faults
.
However, the FDA's different attitudes towards the manufacturers of sitagliptin and valsartan are too obvious
.

The FDA's different attitudes towards the raw material manufacturers of sitagliptin and valsartan are too obvious
.