Monday, September 23, 2019

Zantac recalled because of NDMA contamination

Via the New York Times, more NDMA in the news...: 
The heartburn drug Zantac has been on the market for decades, and was considered safe enough to be sold over the counter and regularly given to infants. 
But on Sept. 13, the Food and Drug Administration said that it had detected low levels of a cancer-causing chemical in samples of the drug, which is also known as ranitidine. The agency advised patients who were taking over-the-counter versions of Zantac to consider switching to other medications. 
On Sept. 18, the drug maker Novartis said that its generic-drug division, Sandoz, had stopped distributing a prescription form of ranitidine worldwide as it investigates the issue. Another major generic manufacturer, Dr. Reddy’s Laboratories, also said it was halting distribution...
So how did it get in there? Via Derek Lowe's post, this Pharmaceutical Technology piece might explain some of it:
Under acidic conditions, sodium nitrite forms nitrous acid, which could react with the residue of dimethylamine in dimethylformamide—the solvent that is used in the tetrazole-forming reaction—to generate NDMA, says Andre. 
There's definitely room for dimethylamine in the synthesis of ranitidine, but where's the nitrous acid come from? Guessing there are lots of folks from Sandoz working on that question right now....

2 comments:

  1. Is this because profit margins on generics are so small that only the shadiest operators will compete in the market?

    ReplyDelete
    Replies
    1. If you read the PharmTech piece there does not appear to be instance with nefarious intentions by the suppliers (unlike cases of melamine additions) but more inadequate focus by both API manufacturers and Regulators in recognizing the probable risks plus use of detection methods specifically looking for the contamination. Although implication is that was an obvious finding I suggest that is oversimplification because performing process risks rely on ranking potential hazardous where combinations of chemistry and conditions leading to a bad by-product from a solvent decomp/impurity can be overlooked/scored low in the overall complexity with greater concerns being examined. Definitely unfortunate and a undesired learning in difficulties inherent in API manufacturing but to jump to shady operators seeking profits seems unreasonable from what I have read.

      Delete