3 companies voluntarily recall varenicline products

that contain impurities that exceed the limit set by MFDS

19 lot release numbers from CTC Bio are recalled…includes Vivozone and Hanmi's products

MFDS plans to publicly announce the safety investigation results… the acceptable amount of daily intake for NNV is ‘37ng’

Results of the safety investigation conducted by the Ministry of Food and Drug Safety on the N-nitroso-varenicline (NNV) impurity that was found in the smoking-cessation aid varenicline showed that the impurity’s risk of harming the human body was very low.

 

However, all drugs that contain over ‘733ng (nanograms)/day’ of NNV will be voluntarily recalled by the companies in line with the standards set by the U.S regulators, Varenicline products that will be voluntarily recalled include those manufactured (consigned products included) by CTC Bio, and consists of 2 lots of Zerocotine tab.

 

from Vivozone, 2 lots of Nicobreak tab.

 

from CTC Bio, and 15 lot of Nokotine S from Hanmi Pharmaceutical.

 

The MFDS announced the results of the NNV safety investigation on the 7th.

 

With NNV detected in all products currently distributed in Korea, the Ministry plans to conduct phased safety management measured to assess its effect on administered patients, set standards on the acceptable level of NNV intake, prepare measures for each amount of NNVs detected, and issue guidelines for HCPs and patients.

 

According to the MFDS, the NNV detected in varenicline products distributed in Korea was very low (16.70~1849ng/day).

 

More specifically, NNV detected in varenicline products that were sold in Korea were: 16.70~1849ng/day for Jeil Pharmaceuticals’ products, 151~632ng/day for Pfizer Korea’s, and 812~1859ng/day for CTC Bio’s products.

 

Products from Jeil Pharmaceuticals and CTC Bio were manufactured in Korea (including consigned products), and Pfizer’s was imported.

 

Assessment of NNV’s effect on the human body also showed a very low level of concern.

 

The safety investigation results were conducted according to the ICH(International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) standards, in consideration of the daily maximum dose of intake, NNV test results, the actual period of administration for patients who participated in the NHIS’s smoking cessation treatment support project.

 

Assessment of NNV’s effect on the human body showed that the NNV brought further cancer risk to 0.194-0.391 out of 100,000 people.

 

The ICH guideline defines the risk to be at a 'negligible level' if the probability is less than 1 in 100,000 people.

 

In consideration of the toxicity value set for NTHP, another nitrosamine-class substance with a very similar structure to NNV, the MFDS set the acceptable amount of daily intake of NNV to 37ng/day.

 

This is the same as the level set by regulation institutions abroad and was determined after consultation with the Central Pharmaceutical Affairs Council.

 

The acceptable amount of daily intake is the amount that increases the probability of developing cancer by 1/100000 when a substance is taken for a lifetime (70 years), apart from the naturally occurring cancer.

 

The MFDS decided to allow the lot release of varenicline products that contain NNV of 185ng/day or less for the time being.

 

This is the same level of standards as the one that was temporarily set by the U.S.

 

The MFDS decision was affected by the fact that the NNV detected in varenicline was at almost no health risk as found from the NNV human impact assessment, and that it is difficult to immediately reduce the NNV amount to less than the acceptable amount of daily intake (37ng/day).

 

The MFDS comprehensively reviewed the US's temporary approval of the lot release at 185ng/day, accessibility to smoking cessation drugs for patients, and advice from the Central Pharmaceutical Affairs Council.

 

In particular, all drugs that are currently in the market whose NNV content exceeds 733ng/day will be voluntarily recalled by the companies.

 

This is in line with the decision made by the U.S.

 

to distribute drugs that contain 733ng/day or less without recall.

 

Accordingly, all lots of the 6 varenicline products from 3 companies that were manufactured by CTC Bio will be voluntarily recalled.

 

The MFDS plans to continue working with the pharmaceutical industry so that the amount of NNV detected can be reduced below the acceptable amount of daily intake as quickly as possible, and will announce the results after the reductions are complete.

 

In addition, the MFDS recommended that patients who have already been prescribed the said products (lot numbers) should not arbitrarily discontinue the use of the drug but consult with his/her doctor or pharmacist on continuing taking the drug or switching to a different medication.

 

If a patient needs to switch to an alternative drug after consultation with his/her doctor or pharmacist, the patient will need to receive a prescription for the alternative smoking cessation treatment from a medical institution participating in the National Health Insurance Service’s smoking cessation treatment support project.