Was metformin recalled
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Metformin Recalls Due to Nitrosamine Impurities
Introduction to Metformin Recalls
Metformin, a widely used medication for managing type 2 diabetes, has faced scrutiny due to the detection of N-nitrosodimethylamine (NDMA), a potentially carcinogenic impurity. This has led to several recalls of metformin products across different regions.
Detection of NDMA in Metformin
The presence of NDMA in metformin was first identified through an international regulatory collaboration. Laboratories worldwide developed and validated analytical procedures to detect nitrosamines in metformin products. From November 2019 to July 2020, 1090 samples of metformin, including both active pharmaceutical ingredients (APIs) and finished dosage forms (FDFs), were tested. NDMA was detected in some batches, with 17.8% of FDF samples exceeding the acceptable intake (AI) limit of 96 ng per day. However, 82.2% of the samples met the quality and safety standards.
Specific Recalls and Regulatory Actions
In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) recalled a specific batch of Rosemont Pharmaceuticals' metformin oral solution due to NDMA levels above the acceptable limit. The recall was a precautionary measure, and patients were advised to continue taking their medication while seeking advice from healthcare professionals. Similarly, the FDA has issued guidance for controlling nitrosamines in drug products, leading to the recall of over 1400 product lots, including metformin, due to unacceptable levels of these impurities.
Investigating the Root Cause of NDMA Formation
Research has been conducted to understand the root causes of NDMA formation during the manufacturing of metformin tablets. Factors such as the use of water and heat during intra-granulation and the nitrite/nitrate content in excipients were identified as key contributors. It was found that certain excipients, like polyvinyl pyrrolidone or hydroxypropyl cellulose, did not lead to detectable NDMA levels even when water and heat were used. However, other excipients, such as hydroxypropyl methyl cellulose, did result in NDMA formation under similar conditions.
Conclusion
The detection of NDMA in metformin has led to significant regulatory actions, including recalls and ongoing investigations into the causes of impurity formation. While the presence of NDMA is a concern, the majority of metformin products have been found to meet safety standards. Regulatory agencies continue to work with manufacturers to mitigate the presence of NDMA in future batches, ensuring the safety and efficacy of metformin for patients.
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