The discovery of DMF in batches of valsartan prompted the online pharmacy to submit its findings to the US Food and Drug Administration (FDA) and demand that action be taken.
Testing by the pharmacy revealed that levels of DMF uncovered were considered safe by FDA regulations, which permits levels of up to 8,800,000 nanograms of daily exposure.
However, the pharmacy suggested that these levels were far higher than those allowed for previously discovered probable carcinogens that prompted recalls, such as N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA). Daily limits for the former are 96 nanograms and 26.5 nanograms for the latter.
Valisure decried the ‘disparity’ between permitted daily exposure limits of NDMA and NDEA, as this “lacks a rational basis and is of significant concern.”
The findings mean that there have now been four probable carcinogens found within sartan medications, including DMF, NDMA, NDEA and N-Nitroso N-Methyl 4-amino butyric acid (NMBA).
Valisure explained its decision to submit a Citizen Petition in a statement: “Given the increased risk to public safety, the concern of medical practitioners regarding DMF in pharmaceuticals, and the fact that FDA did not amend the acceptable intake of DMF or take other appropriate action following the chemical’s reclassification to Group 2A status by WHO and IARC, Valisure seeks to utilize this Citizen Petition to bring these concerns directly to the attention of the commissioner and the FDA, and request that they take action.”
DMF is a Class 2 solvent that is used in the production of active pharmaceutical ingredients (APIs) and the pharmacy linked the ‘switch’ in the manufacturing industry to its use in API production to the formation of the probable carcinogens in sartan medication.
The pharmacy’s petition requests five actions from the FDA to rectify this perceived error, paraphrased below:
- To lower the accepted intake/permitted daily exposure of DMF
- Request a recall of identified lots of valsartan contaminated with DMF
- Investigate the issue further
- Provide information to the public
- Pass regulation requiring ‘robust’ testing of the chemical content of batches, and issue guidance requesting such testing and verification
The Citizen Petition listed the APIs discovered to contain DMF, the levels contained within the API and the distributors of the product. The distributors noted include Amneal, Macleods and Novartis, amongst other companies.
Valisure suggested that it will take a financial loss as a result of the findings – through choosing not to sell affected lots of valsartan that it had acquired and then being unable to receive a refund due to the current FDA guidance on the acceptable daily exposure limit for DMF.