Industry feels growing pressure on metformin risk

MFDS wants report on metformin complete product and ingredient manufacturing record

Companies fearing imminent government action, initiate self-test on contamination

Ministry of Food and Drug Safety (MFDS)

The pharmaceutical industry’s concern over metformin impurity contamination is growing.

 

The industry’s eyes are focused on the government’s action following its ongoing metformin usage status review.

 

Some of pharmaceutical companies are promptly equipping themselves with impurity analyzer a self-testing.

 

◆MFDS initiates metformin usage status review, the industry fears of follow-up action An industry source reported on Dec.

 

15 that Korea’s Ministry of Food and Drug Safety (MFDS) has ordered pharmaceutical companies to assess manufacturing record of pharmaceutical product containing ‘metformin hydrochloride’ and investigate used active pharmaceutical ingredient.

 

MFDS asked companies to report total number of drug items consisting of metformin substance, names and number of manufactured items, and names and number of non-manufactured items until Dec.

 

17.

 

Molecular structure of metformin

Pharmaceutical companies have to provide all information of items even covering ones in distribution at the moment, considering use-by date of complete products.

 

For example, when an items’ use-by date is three years, then the item’s entire manufacturing record after December 2016 should be looked into.

 

The ministry is also calling for a full report on active ingredients used in the metformin products.

 

It means the ministry means to collect detailed information on DMF registration number and manufacturing plant of a complete product containing the ingredient under each serial number.

 

The procedure resembles the ranitidine and nizatidine cases.

 

When they find an issue in specific active ingredient and complete drug, the ministry can take a fast and accurate action based on the information submitted by companies.

 

The pharmaceutical industry predicts the government direction is a part of the ministry’s preparation process, in case impurity is discovered in metformin medicine.

 

Before the government body took an action on ranitidine and nizatidine cases, the ministry had reviewed detailed information on complete product and the active ingredients.

 

MFDS had immediately ordered a sales ban on drugs with valsartan when Europe decided to recall the products, but it held back on the action for ranitidine and nizatidine until the thorough review on complete products and the ingredients was completed.

 

The risk of metformin impurity broke out from Singapore.

 

On Dec.

 

4, Singapore’s Health Sciences Authority (HSA) recalled three items out of 46 metformin containing drugs they investigated.

 

The result confirmed contamination of N-Nitrosodimethylamine (NDMA) has surpassed daily acceptable level.

 

Since then, the U.S., Europe and Japan initiated impurity testing on metformin drugs.

 

All three regions are recommending companies to conduct self-testing on NDMA levels in their metformin drugs.

 

◆Companies initiating impurity self-tests and purchasing analyzer Companies in Korea are also encouraged to run self-tests on their metformin-containing items.

 

So far the ministry has not officially instructed companies to test impurity in metformin ingredients.

 

In fact, the ministry has not even ordered them to test NDMA level in complete product or announced a plan to collect all items for further investigation.

 

MFDS’ lack of instruction could be because of the U.S.

 

and Europe have not ordered for a recall on products with alarming impurity level, and also because the problematic metformin ingredient and complete product with the ingredient have not even been imported to Korea.

 

Moreover, there has not been an official procedure of NDMA testing presented by the ministry.

 

The complete products with contaminated metformin recalled in Singapore have not been imported to Korea, yet.

 

However, it has not been confirmed yet if the active ingredient used in the recalled product has been used in Korea.

 

Apparently, the Singaporean regulator has decided to recall the products after testing complete products, not the active ingredient.

 

The pharmaceutical companies in Korea have no other choice, but to test their metformin products according to the active pharmaceutical ingredient impurity risk management measure the ministry has unveiled recently.

 

While announcing the investigation result of nizatidine contamination last month, MFDS ordered companies to conduct a self-test on all of their synthetic active ingredients for impurity like NDMA.

 

Accordingly, synthetic ingredient manufacturer and importer, as well as complete product companies, have to evaluate contamination risk in drugs either during manufacturing or storing processes.

 

Pharmaceutical impurity risk management initiative unveiled by MFDS last month

Moreover, pharmaceutical companies have to immediately report any discovery of impurity to MFDS after conducting self-evaluation on suspected items with risk of NDMA-like impurity contamination.

 

Basically, metformin became the first substance to be ‘suspected for contamination risk’ since the ministry’s impurity risk management initiative.

 

The industry seems to be in process of attempting self-analyze NDMA level in metformin medicine.

 

However, the testing process has not been so simple without an official testing procedure and lack of laboratories with proper analysis equipment.

 

Currently, only nizatidine-containing products verified with approved level of NDMA can be distributed, but the testing laboratories are unable deliver testing results in requested time as they are backed-up with all companies with nizatidine products.

 

MFDS has ordered pharmaceutical companies to supply nizatidine-containing item with passing level of cancer-causing NDMA contamination (less than 0.32ppm), verified by testing done for each item serial number.

 

The test can be done by Korean Good Manufacturing Practice (GMP) certified manufacturer, MFDS designated quality test institute, city and provincial-managed environment research lab and Korean Pharmaceutical Traders Association.

 

MFDS ordered pharmaceutical companies to test NDMA level in nizatidine medicine before supplying

Some of pharmaceutical companies are even considering on purchasing testing equipment to run it by themselves.

 

But an analyzer costing up to 300 million to 500 million won, beside the six-figure annual maintenance, cost is definitely putting a strain on the company.

 

A pharmaceutical company insider commented, “The company is taking account of equipping impurity risk examination system as its own quality management program.

 

We are also discussing possibility of sharing an ownership and purchase cost of the analyzer”.