MFDS to wait and see self-test results on metformin

MFDS hasn’t made official order to pharmaceutical companies about metformin contamination

Basically encouraging self-investigation, applying new contamination risk management initiative

Full investigation could be ordered in case impurity found on exceeding level

Ministry of Food and Drug Safety (MFDS)

The government seems to have decided to encourage pharmaceutical companies to run their own impurity contamination test on metformin drugs.

 

Unlike the ranitidine and nizatidine incidents, the government means to wait and see the companies’ self-investigation results, rather than to take an action by itself.

 

Basically, metformin would be the first substance to be applied with the recently unveiled impurity risk management initiative.

 

However, the possibility still exists for the government to immediately call for sales ban and other follw-up measures, when a exceeding level of impurity is found in a product, either in Korea or overseas.

 

According to the industry source on Dec.

 

12, Korea’s Ministry of Food and Drug Safety (MFDS) has not made any official order to pharmaceutical companies regarding findings of cancer-causing impurity in metformin.

 

On Dec.

 

4, Singapore’s Health Science Authority (HSA) has decided to recall three out of 46 metformin products tested.

 

Apparently, the regulator found N-nitrosodimenthylamin (NDMA) exceeding an acceptable level of daily consumption in metformin products.

 

Since then, the U.S.

 

and European health regulators have also started probing on contaminated metformin products.

 

The U.S.

 

Food and Drug Administration (FDA) is reportedly investigating NDMA discovered in metformin products available in the U.S.

 

It also stated it would recommend recalling products with exceeding levels of NDMA contamination.

 

The European Medicines Agency (EMA) has ordered companies to conduct NDMA contamination testing.

 

Japan’s Ministry of Health, Labor and Welfare recently ordered metformin containing product manufacturers and importers in Japan to analyze and report risk of NDMA contamination in the substance and complete products.

 

So far, MFDS has only stated it would “review investigation results”, and no other specific orders have not been given to the companies.

 

The ministry has not yet ordered the companies to investigate NDMA in metformin active agent or complete product, nor has it stated the ministry would directly collect and investigate the substance.

 

The ministry’s reaction is contrasting from the follow-up measures it had with other pharmaceutical impurity risk incidents.

 

When the European regulator announced it would recall all valsartan products, the Korean ministry immediately banned sales of products with the same active ingredient.

 

And after the sales ban was ordered in the U.S., the ministry once said “nothing to worry about”, but soon after it ordered an all-product ban.

 

Actions on nizatidine followed the ranitidine sales ban.

 

After collecting and testing active ingredient and complete product with similar chemical structure as ranitidine, MFDS banned sales on 13 items with unacceptable level of NDMA.

 

It could be interpreted that the authority is trying to encourage companies to voluntarily test their metformin products.

 

Neither of the U.S.

 

or Europe has called for a recall due to exceeding level of the contamination.

 

And the complete products reported with the impurity to date are not available in Korea, yet.

 

MFDS official explained, “We have already asked companies to test the impurity in all products themselves”.

 

It also means the recently introduced active ingredient impurity risk management initiative would be applied on metformin.

 

In fact, MFDS has already asked pharmaceutical companies to run NDMA-like impurity test on all synthetic active agents, when announcing the investigation result of nizatidine medicine.

 

Accordingly, synthetic ingredient manufacturer and importers, as well as complete product companies, have to evaluate risk of impurity contaminated during the process of manufacturing or storing.

 

Pharmaceutical companies suspecting a risk of discovering NDMA and other harmful impurity in their product should immediately conduct a voluntary test and has to report MFDS as soon as possible when it is actually found.

 

The impurity risk evaluation and testing should be conducted voluntarily, and the result of risk evaluation should reported by May 2020, and the result of test by May 2021.

 

Pharmaceutical impurity risk management initiative presented by MFDS last month

Since MFDS has introduced the impurity management initiative, metformin basically became the first case of ‘medicine with high risk’.

 

In other words, MFDS is unlikely to test metformin itself, as of now.

 

Moreover, metformin being a commonly used agent seems to make MFDS hesitant about testing the products proactively.

 

Metformin is the most commonly prescribed first-line treatment for patients with Type 2 diabetes to control glucose level.

 

In Korea alone, 642 of approved complete products contain metformin.

 

Practically, all pharmaceutical companies have at least one metformin medicine.

 

Compared to valsartan and ranitidine market, metformin has a far larger market volume.

 

Pharmaceutical industry research firm UBIST reported outpatient prescription market volume of metformin product reached 420 billion won last year.

 

It soared 63.4 percent in four years from 257.1 billion won in 2014.

 

Currently banned ranitidine products generated about 200 billion won as outpatient prescription, but metformin market easily doubles the ranitidine market.

 

A single dose of metformin is priced at less than a hundred one with reimbursement.

 

Considering the pricing, metformin’s usage volume is overwhelmingly bigger than ranitidine.

 

Yearly trend of outpatient prescription volume of metformin product (unit: KRW 100 million) Source: UBIST

If the testing confirms metformin is contaminated with NDMA during the process of storing, active agent and complete product should be reviewed by each serial number.

 

In such case, millions of serialized products would have to be investigated.

 

It is physically impossible for MFDS to directly investigate them all.

 

However, the ministry may initiate a full investigation, depending on the updates from home and abroad.

 

The ministry’s hands-on investigation would be inevitable when active ingredient or complete product in Korea is found with exceeding level of impurity is reported from overseas.

 

And even when a Korean company reports any case of NDMA contamination exceeding an acceptable level, full investigation is likely follow.