Investigation ongoing – statement to be updated as more information is available
FDA alerts patients and health care professionals to Sandoz’s losartan potassium and hydrochlorothiazide recall of one lot due to NDEA
Update [11/9/2018] FDA is alerting patients and health care professionals to Sandoz’s voluntary recall of one lot – JB8912 – of losartan potassium and hydrochlorothiazide 100mg/25mg tablets, that contain losartan, an angiotensin II receptor blocker (ARB), and hydrochlorothiazide, a diuretic, used in combination for the treatment of hypertension. Sandoz’s product was made using an active pharmaceutical ingredient (API) that has tested positive for NDEA. The API was manufactured by Zhejiang Huahai Pharmaceutical Co. Ltd, which is on import alert.
Sandoz’s losartan drug products make up less than 1 percent of the total losartan drug products in the U.S. market.
FDA continues to investigate the presence of NDEA and NDMA, which are probable human carcinogens, in ARBs and is taking swift action when it identifies unacceptable impurities in API and finished drug products.
FDA reminds patients taking this medication or any recalled ARB to continue taking their current medicine until their pharmacist provides a replacement or their doctor provides an alternative treatment option. It also is important to know not all ARBs contain NDEA or NDMA, so pharmacists may be able to provide a refill of medication not affected by the recall, or doctors may prescribe a different medication that treats the same condition.
The links below are to FDA-published testing methods to provide options for regulators and industry to detect NDMA and NDEA impurities. These methods should be validated by the user if the resulting data are used to support a required quality assessment of the API or drug product, or if the results are used in a regulatory submission.
- The combined headspace method is a GC/MS method that allows determination of both NDMA and NDEA simultaneously in sartan drug substance and drug products.
- The combined direct injection method is a GC-MS/MS method that allows for determination of both NDMA and NDEA simultaneously in sartan drug substance and drug products.
The European Directorate for the Quality of Medicines (EDQM) has also published methods to detect NDMA and NDEA. FDA has not validated EDQM’s methods.
FDA alerts patients and health care professionals to ScieGen’s irbesartan recall due to NDEA
Certain irbesartan products labeled as Westminster Pharmaceuticals Inc. and GSMS Inc. recalled
Update [10/30/2018] FDA is alerting patients and health care professionals to ScieGen’s voluntary recall of certain lots of irbesartan, an angiotensin II receptor blocker (ARB), because they contain N-Nitrosodiethylamine (NDEA), a known animal and suspected human carcinogen (causes cancer). FDA laboratory testing confirmed NDEA in some lots of ScieGen’s irbesartan. ScieGen’s irbesartan products are labeled as Westminster Pharmaceuticals and Golden State Medical Supply, Inc. (GSMS). See the list of irbesartan products under recall. This is the first non-valsartan drug product the agency has found to contain the NDEA impurity.
ScieGen’s recall affects about 1 percent of the irbesartan drug products in the U.S. market.
Additionally, Aurobindo, which manufactures the active pharmaceutical ingredient (API) for ScieGen’s irbesartan products, is recalling all unexpired lots of its irbesartan API supplied to the U.S. market with NDEA. FDA and Aurobindo laboratory testing confirmed NDEA in certain lots of their irbesartan API.
FDA reminds patients taking any recalled ARB to continue taking their current medicine until their pharmacist provides a replacement or their doctor provides an alternative treatment option. Not all ARBs contain NDEA or N-Nitrosodimethylamine (NDMA), a probable human carcinogen previously found in certain recalled valsartan products, so pharmacists may be able to provide a refill of medication not affected by the recall, or doctors may prescribe a different medication that treats the same condition.
To date, ScieGen is the only manufacturer of irbesartan drug products found to contain NDEA. FDA continues to test all ARBs for the presence of impurities and has publicly posted two methods for manufacturers and regulatory agencies around the world to test their ARBs for the unexpected NDMA and NDEA impurities. The combined headspace method and the combined direct injection method can detect and quantify NDMA and NDEA simultaneously in ARB API and finished drug products.
FDA continues to work with API and drug manufacturers to ensure their products are not at risk for NDMA or NDEA formation. The agency reminds manufacturers they are responsible for developing and using suitable methods to detect impurities, including when they make changes to their manufacturing processes. If a manufacturer detects new or higher levels of impurities, they should fully evaluate the impurities and take action to ensure the product is safe for patients.
For additional information about ARB products, see:
FDA updates recalled valsartan-containing product information
Update [10/24/2018] FDA continues to evaluate valsartan-containing products and other angiotensin II receptor blockers (ARBs), and has updated the list of products included in the recall to add one additional lot of RemedyRepack.
FDA releases additional NDMA/NDEA detection method
Update [10/16/2018] FDA is posting a gas chromatography-tandem mass spectrometry (GC-MS/MS) methodutilizing liquid injection for detecting the presence of impurities N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA) in valsartan drug products.
This method provides an additional option for regulators and industry to detect NDMA and NDEA impurities. This method can be used alone or in combination with the combined gas chromatography-mass spectrometry (GC/MS) headspace method the agency recently posted. Like the previously posted methods, this method should be validated by the user if the resulting data are used to support a required quality assessment of the API or drug product, or if the results are used in a regulatory submission.
FDA releases method for detection and quantification of both NDMA and NDEA
Update [10/11/2018] ] FDA is posting a redeveloped combined gas chromatography-mass spectrometry (GC/MS) headspace method for detecting the presence of impurities N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA) in valsartan drug products.
FDA previously posted a GC/MS method for detection of NDMA in valsartan products. Upon detection of NDEA in valsartan products manufactured by Zhejiang Huahai Pharmaceuticals, FDA redeveloped the testing method so that it can be used to detect and quantify levels of both NDMA and NDEA. This method should be validated by the user if the resulting data are used to support a required quality assessment of the API or drug product, or if the results are used in a regulatory submission.
FDA is also working on a GC/MS direct injection method for detection of NDMA and NDEA. We will post the method when it is available. This will provide an additional option for regulators and industry to use to detect both impurities.
FDA posts laboratory analysis of NDMA levels in recalled valsartan products
Update [10/5/2018] FDA posted laboratory test results showing NDMA levels in recalled valsartan products. FDA will also post test results and an assessment of the cancer risk from NDEA when they are available.
FDA places Zhejiang Huahai Pharmaceuticals on import alert
Update [9/28/2018] FDA placed Zhejiang Huahai Pharmaceuticals on import alert on September 28, 2018, to protect U.S. patients while the active pharmaceutical ingredient (API) manufacturer fully determines how impurities were introduced into its API and remediates its quality systems. The import alert stops all API made by ZHP and finished drug products made using ZHP’s API from legally entering the United States. FDA’s action follows a recent inspection at ZHP’s facility.
FDA reminds manufacturers that it is their responsibility to develop and use suitable methods to detect impurities, including when they make changes to their manufacturing processes. If a manufacturer detects new or higher levels of impurities, they should fully evaluate the impurities and take action to ensure the product is safe for patients.
FDA updates recall lists and releases method for the detection and quantification of NDMA in valsartan
Update [9/24/2018] FDA has updated the list of valsartan products not under recall with five Teva products that were not previously on either list.
Update [8/24/2018] Torrent Pharmaceuticals Limited is expanding its voluntary recall. FDA has updated the list of valsartan products under recall.
Update [8/22/2018] Torrent Pharmaceuticals Limited is expanding its voluntary recall to all lots of unexpired valsartan-containing drug products due to the detection of NDMA in the active pharmaceutical ingredient (API) manufactured by Zhejiang Huahai Pharmaceuticals.
RemedyRepack, a repackager of Torrent’s valsartan/amlodipine/hydrochlorothiazide (HCTZ) tablets, has also recalled.
FDA has updated the list of valsartan products under recall and the list of valsartan products not under recall.
Additionally, FDA is releasing a gas chromatography-mass spectrometry (GC/MS) headspace method for manufacturers and regulators to detect and quantify NDMA in valsartan API and finished drug products. The agency is using this method to test potential NDMA-containing APIs and drug products. This method should be validated by the user if the resulting data are used to support a required quality assessment of the API or drug product, or if the results are used in a regulatory submission.
Here’s another great article on High Blood Pressure Meds recalls, you may find interesting
Original source. Follow the investigation here.