Seven times stricter standards

Instructions to ship only products within the permissible intake per day... 100 domestic pharmaceuticals in the affected area

7 times stricter than the temporary standard applied to the recall of Januvia, pharmaceutical companies re-examined quality control

Panoramic view of the Ministry of Food and Drug Safety

Health authorities have prepared new standards for managing impurities in Januvia, a diabetes treatment.

 

Prior to the release of Januvia generics, pharmaceutical companies were requested to only ship products within the newly set standard.

 

Pharmaceutical companies are busy with quality control by presenting a standard that is seven times stricter than the temporary acceptance standard applied at the time of the recall of Januvia impurity products.

 

According to the industry on the 25th, the Ministry of Food and Drug Safety recently sent an official letter to pharmaceutical companies with instructions on safety measures and information on nitrosamine impurities in drugs containing ‘sitagliptin’.

 

The MFDS determined that the nitrating agent among the additives of Sitagliptin generated the impurity NTTP during the manufacturing or storage process of the finished drug.

 

It means that it has a chemical structure in which impurities are generated during the manufacturing process of sitagliptin.

 

It suggested the permissible daily intake of Sitagliptin NTTP as 37ng and instructed pharmaceutical companies to implement safety measures.

 

The MFDS ordered, “We will conduct an NTTP test and inspection for impurities and only ship products within the permissible daily intake (37ng/day), and if impurities are detected as a result of the test, we will take step-by-step measures according to the level of detection.” The MFDS ordered pharmaceutical companies to conduct stability tests so that the NTTP can be managed at 30% or less of the acceptable standard during the period of use of the finished product of sitagliptin.

 

In case the standard is exceeded or there is a concern, it is instructed to immediately report it to the Ministry of Food and Drug Safety.

 

Sitagliptin is a DPP-4 inhibitory diabetes treatment, and MSD's Januvia is the original drug.

 

Recently, Chong Kun Dang acquired the domestic sales rights of Januvia.

 

After Januvia's patent expires in September, domestic pharmaceutical companies are preparing to release generics.

 

In other words, the Ministry of Food and Drug Safety presented the impurity control standard before the release of Januvia generics and started a preliminary inspection.

 

The danger of impurities in Januvia was raised last year.

 

In August of last year, the European Medicines Agency (EMA) instructed Januvia to investigate the possibility of detecting a new NTTP impurity.

 

As a result of MSD's impurity analysis at the time, NTTP was found, but it was not detected above the standard level, so it did not lead to a recall action.

 

In Korea, in March, MSD Korea voluntarily recalled two lot numbers (U010253, U012914) of ‘Januvia 50mg’.

 

At the time, MSD Korea said, "The NTTP level detected in Januvia slightly exceeds the temporary release standard (maximum 246.7ng/day)." The Ministry of Food and Drug Safety suggested 246.7ng/day as the standard for the temporary release of Januvia, and Januvia exceeded this standard and voluntarily recalled it.

 

The limit for sitagliptin impurities set by the Ministry of Food and Drug Safety this time is 37 ng/day, which is one-seventh of the temporary release standard applied at the time of Januvia recovery.

 

This means that the standard was set seven times stricter than the temporary release standard.

 

If Januvia's recalled product was detected with NTTP at the temporary release standard level, it means that it exceeded the standard set by the Ministry of Food and Drug Safety by about 7 times.

 

An official from the Ministry of Food and Drug Safety said, “The temporary acceptance standard is a standard that is applied when there is a concern about the supply disruption of the drug.” Explained.

 

This means that the NTTP standard for sitagliptin has been set based on the same standard as other medicines because there is no problem with drug supply and demand even if impurities problems arise in some products when Januvia generics are poured out.

 

It is known that many pharmaceutical companies conducted sitagliptin NTTP quality control based on temporary release standards.

 

However, as the standard proposed by the Ministry of Food and Drug Safety is seven times stronger than the temporary acceptance standard, pharmaceutical companies are forced to conduct NTTP inspections according to more stringent standards.

 

Since impurities in Sitagliptin preparations must be controlled within 30% of the allowable limit during the period of use, pharmaceutical companies complain that the quality control standards have become too strict.

 

Some companies have begun adjusting their impurity quality control plans as the Ministry of Food and Drug Safety presents stricter standards than those set by itself.

 

According to the Ministry of Food and Drug Safety, 100 domestic pharmaceutical companies have approved 715 products containing Sitagliptin and are waiting for the release date.

 

According to UBIST, a pharmaceutical research institute, a total of 109.4 billion won in outpatient prescriptions for sitagliptin-containing drugs was jointly made last year.

 

Januvia and Janumet raised 40.5 billion won and 68.9 billion won, respectively.

 

As Januvia is forming a large market, domestic pharmaceutical companies are preparing to enter the generic market indiscriminately.