FiercePharma reports: GlaxoSmithKline sold its $155 million Zantac (ranitidine drug) plant in India to Hetero Labs.

Three years ago, GSK invested US$155 million to open a factory in Vemgal, India, and its gastrointestinal drug market is expected to be strong. But eventually brought trouble to GSK. Recently, its board of directors approved the sale of the plant to Indian pharmaceutical company Hetero Labs for a price of US$25 million, which is only a small part of its cost.

Incident involving genotoxic impurities! Pharmaceutical giant GSK is going to sell its $155 million factory!

The factory officially opened in 2018. At that time, it had about 300 employees and had an annual production capacity of 8 billion tablets and 1 billion capsules. But a year later, Zantac, the main product of the plant, was recalled globally because of the first carcinogen contamination found in India.

GlaxoSmithKline withdrew the brand-name drug (only sold outside the United States) because Sanofi withdrew its US brand-name drug, and many other drugmakers also withdrew generic drugs. At the time, local media reported that GSK products were made with active ingredients produced by Indian pharmaceutical manufacturers.

Previously: The regulatory authorities in China, the United States and Europe have all put forward requirements on ranitidine:

The US Food and Drug Administration (FDA) announced in April last year that it required manufacturers to immediately withdraw all prescription and over-the-counter (OTC) ranitidine drugs from the market. This is the latest step in the ongoing pollutant research of ranitidine (usually the brand name drug Zantac), which is called N-nitrosodimethylamine (NDMA). The agency has determined that the impurity in certain ranitidine products will increase over time and stored at above room temperature, and may cause consumer exposure to exceed unacceptable levels of this impurity. Due to the immediate withdrawal of market requirements, ranitidine products will not be used in new or existing prescription or over-the-counter drugs in the United States.

"The FDA is committed to ensuring that the drugs taken by Americans are safe and effective. We will make every effort to investigate potential health risks and provide recommendations to the public based on the best available scientific knowledge. In many of the samples we tested, we did not observe The unacceptable level of NDMA. However, since we do not know how long or how long the product may have been stored, we decided that unless the quality is guaranteed, the product should not be sold to consumers and patients." CDER Director Janet Woodcock , MD said, "The FDA will continue to work to ensure that the impurities in other drugs do not exceed acceptable limits so that patients can continue to take them without worry."

NDMA is a possible human carcinogen (a substance that may cause cancer). In the summer of 2019, the FDA realized that NDMA was found in ranitidine in an independent laboratory test. Low levels of NDMA are usually consumed in the diet, such as the presence of NDMA in food and water. These low levels will not increase the risk of cancer. However, persistently high exposure levels may increase the risk of cancer in humans. The FDA conducted a thorough laboratory test and found that the NDMA content in ranitidine was low. At that time, the agency did not have enough scientific evidence to recommend whether individuals should continue or stop taking ranitidine, and it continued to investigate and warned the public of possible risks in September 2019, and considered the use of other OTC and prescription drug treatments.

The information provided by third-party laboratories suggests that the new FDA test and evaluation results confirm that the NDMA content of ranitidine will increase even under normal storage conditions, and it is found that the NDMA content of ranitidine will increase at higher temperatures (including the product may be used during use). In samples stored at the temperature of exposure), NDMA will increase significantly. Distributed and processed by consumers. Tests also show that the earlier ranitidine products are produced, or the longer the time since production, the higher the NDMA content. These conditions may increase the NDMA level in ranitidine products above the acceptable daily intake limit.

The FDA announced today that it will send a letter to all ranitidine manufacturers requesting them to withdraw their products from the market. The FDA also recommends that consumers taking OTC ranitidine stop taking any tablets or liquid preparations they currently have, dispose of them properly, and stop buying. For those who wish to continue to treat their condition, other approved OTC products should be considered. Patients taking ranitidine prescriptions should discuss other treatment options with healthcare professionals before stopping drug treatment, because ranitidine has been approved for multiple drugs with the same or similar uses as ranitidine, none of them Take the same risks that NDMA brings. So far, FDA testing has not found NDMA in famotidine (Pepcid), cimetidine (Tagamet), esomeprazole (Nexium), lansoprazole (Prevacid) or omeprazole (Prilosec) .

In view of the current COVID-19 pandemic, the FDA advises patients and consumers not to bring drugs to the drug recovery location, but to follow the specific disposal instructions in the medication guide or package insert, or follow the steps recommended by the agency, including the following methods safely Dispose of these medicines at home.

FDA will continue to conduct continuous review, monitoring, compliance and drug quality work in each product area, and will continue to cooperate with drug manufacturers to ensure that safe, effective and high-quality drugs are provided to the American public. The FDA encourages healthcare professionals and patients to report any adverse reactions or quality issues of human medications to the agency's MedWatch Adverse Event Reporting Program.

Previously, the National Pharmacopoeia Commission issued a public announcement that it planned to revise the relevant labeling of ranitidine raw materials and preparations, mainly related to genotoxic impurities.

Following the US request for ranitidine products on the market, the European Union EMA issued a document on April 30. The EMA’s Human Medicines Committee (CHMP) recommended that all ranitidine drugs be suspended in the EU because of the existence of a claim It is a low-content impurity of N-nitrosodimethylamine (NDMA). NDMA is classified as a possible human carcinogen.

Degradation of the drug will generate NDMA, which will cause the NDMA content in the drug to exceed the standard. It is indeed very troublesome. Reducing the shelf life or changing the storage conditions will directly reduce the economics of the drug. When there are many alternative drugs, ranitidine Is it cold?

According to animal studies, NDMA is classified as a possible human carcinogen (a substance that may cause cancer). It is present in certain food and water supplies, and if ingested at very low levels, it will not cause harm.

The existing safety data do not show that ranitidine increases the risk of cancer, and any possible risk may be very low. However, higher than acceptable levels of NDMA have been found in several ranitidine drugs, and there are unresolved issues regarding the source of impurities.

There is evidence that the degradation of ranitidine itself will lead to the production of NDMA, and its shelf life level will continue to increase. It is not clear whether NDMA can also be formed from ranitidine in the body. Some studies show that it can, while others cannot. In view of uncertainties, CHMP recommends suspending the use of these drugs in the European Union.

The drug ranitidine is used to reduce gastric acid levels in patients with diseases such as heartburn and gastric ulcer. There are other options, and if a patient needs advice on which medicine to take, they should contact their healthcare professional.

Many ranitidine drugs have not been marketed in the EU for several months. This is because the national authorities have recalled them as a preventive measure during the EMA review.

EMA also provided recommended conditions for banning ranitidine, including requiring companies to provide more data.

Since 2018, NDMA and similar compounds, nitrosamines, have been detected in many drugs, and EU regulatory agencies have taken action to determine possible sources of impurities and set strict new requirements for manufacturers.

EMA will continue to work with national authorities, European Commission EDQM and international partners to ensure that effective measures are taken to prevent the presence of these impurities in drugs.