The Ministry of Food and Drug Safety Thursday offered a briefing to pharmaceutical firms over the suspension of ranitidine-containing heartburn treatments, explaining why it had to ban the manufacturing, importing, and selling of ranitidine drugs.
Earlier, the regulator said it found that NDMA levels in seven ranitidine raw materials exceeded the provisional standard, following the U.S. Food and Drug Administration’s announcement on Sept. 14 that it detected low levels of NDMA in ranitidine medicines.
Unlike the valsartan recall last year, the authorities are likely to kick ranitidine out of the market for good because it was unclear why NDMA was found, and ranitidine’s heterogeneity makes it difficult to prove safety. In the case of valsartan, drug companies were able to sell valsartan again after submitting safety test data.
“If companies submit safety test materials, we will review them. But I don’t think proving safety will be easy,” said Kim Myung-ho, director of the Pharmaceutical Safety Bureau at the Ministry of Food and Drug Safety. “European and U.S. officials do not know what caused NDMA in ranitidine, and drug companies are withdrawing ranitidine medicines.”
The following is excerpts of questions and answers at the ministry’s briefing for pharmaceutical firms.
Question: According to the food and drug safety ministry, ranitidine raw materials had zero to 53.55 ppm of NDMA. Are the different levels of NDMA related to the date of manufacturing of the raw materials?
Answer: NDMA levels were higher in those manufactured first. But they were estimates, not accurate numbers. Some ranitidine drugs were made at the same site, but one had NDMA, but the other did not. This is only an assumption but we think ranitidine seems to react to the change of the environment such as time or temperature.
Q: If a company proves ranitidine raw materials and finished products have NDMA levels below the standard, do you plan to allow a resumption of sale?
A: If they submit safety test data for the resumption of the supply, we will review them. But it will not be easy. NDMA levels are different even within a lot, and the levels depend on which point you take it. It may be difficult to prove safety in such a heterogeneous condition. The ministry has to secure the safety first and approve the sale, but honestly, we cannot guarantee the safety of ranitidine.
Q: Do you plan to test NDMA levels in ranitidine-containing finished products? Is there a chance that NDMA will not be found in finished drugs? Do you have a plan for evaluating the risks of taking ranitidine?
A: We have a plan for NDMA testing for finished products. We will review whether to disclose results later. When we found a carcinogen in valsartan last year, we detected NDMA in both raw materials and finished goods. It will not be much different this time. Even if it's not detected, it's hard to say it is safe because of the heterogeneity of ranitidine. As with the valsartan case, we plan to assess ranitidine’s overall impact on humans, taking into account the dosage and duration of the medication.
Q: Due to the wide range of ranitidine grades and targets for recall, the ranitidine recalls within a short time will be difficult. Is it possible to extend the deadline of the recall?
A: A drug company must request an extension of the due date. We understand it can take much time because companies have various kinds of ranitidine drugs. A drugmaker should note that it must cite the reason for the request of the deadline extension.