Follow-up of impurity inspection

Develop NDMA management guidelines

The MFDS received the results of testing and testing of Nitrosamine impurities from domestic pharmaceutical companies, and prepared safety management guidelines as a follow-up measure.

 

This guideline is for safety management of N-Nitrosamines, a mutagenic and carcinogenic impurity among drugs, and it should be implemented by raw and finished drug manufacturers and importers to reduce or prevent impurities within the daily intake allowance.

 

Starting with high blood pressure medicine (Valsartan) in 2018, tuberculosis medicine (Rifampicin) in 2021 as Nitrosamines were detected in drugs every year until Rifampicin), and new mutagenic impurities were recently detected, the MFDS received a test report of the company's own test on the evaluation items that may occur until the 31st of last month.

 

The MFDS will continue to review impurities that may be included in medicines through close cooperation with overseas regulators and recommend appropriate measures to related pharmaceutical companies.

 

According to the guidelines, apart from the MFDS' review of impurities, pharmaceutical companies should closely examine the raw material drug synthesis process and the manufacturing process of finished drugs using currently available science and technology to evaluate the potential cause and possibility of impurity generation.

 

Pharmaceutical companies should check all impurities that may occur in the process of synthesizing and storing raw materials, manufacturing and storing finished drugs, evaluate the mutagenicity of the impurities, and if mutagenicity or carcinogenicity is confirmed, the risk of carcinogenesis is less than 1/100,000.

 

(Q)SAR methods can be used to predict bacterial mutagenicity test results using a computer, appropriate management methods can be applied based on structural warnings, or bacterial mutagenicity tests can be conducted directly for specific impurities Nitrosamines impurities are compounds with potential carcinogenicity or mutagenicity that can occur mainly when they are combined under conditions where Amine and Nitrosating agent can react.

 

The causes of Nitrosamines impurities in drugs identified so far can be classified as risk factors related to the manufacture and storage of raw and finished drugs, and there are also risk factors related to GMP.

 

When detecting impurities, pharmaceutical companies should report data on the possibility of occurrence to the MFDS, the cause of occurrence (including the estimated cause), the detection amount, and the daily intake allowance.

 

According to the step-by-step measures prepared and distributed by the MFDS, pharmaceutical companies should compare the amount of impurity detection and acceptance criteria, take necessary measures such as voluntary recovery and reduction of impurities in the market, and submit related matters to the MFDS.

 

It will review necessary measures based on information collected from pharmaceutical companies' reporting of impurity detection and overseas regulatory agencies.

 

If it is deemed necessary for the safety management of drugs in circulation in Korea, it is planned to instruct to evaluate the possibility of impurities and conduct test tests on specific drugs.