The FDA, whose efforts to safeguard the U.S. drug supply have led to shortages of certain blood pressure drugs, is setting its own rules aside on a probable cancer-causing impurity. Drugmakers can make losartan with the impurity above its prescribed level for six months while the supply of clean drugs is ramped up.
The FDA’s logic? Its scientists say the risk from the impurity is low to begin with, so exposure for another six months will not make an appreciable difference. The FDA thinks that risk is better than the chance of patients having heart trouble because they can’t get any losartan.
The action, announced Wednesday, applies only to losartan and only to the impurity N-Nitroso-N-methyl-4-aminobutyric acid (NMBA), one of three that the FDA has determined can occur during the manufacturing of the blood pressure drugs losartan, valsartan and irbesartan.
“Distributing losartan containing NMBA up to 9.82 ppm, will help maintain adequate losartan supply while companies obtain approval for manufacturing processes that produce nitrosamine-free losartan for patients,” the FDA said.
The FDA said that when drugmakers through testing find that their losartan supplies fall between the interim acceptable intake limit they must notify the agency. It will determine on a case-by-case basis whether to allow the drugs on the market.
The initial discovery of tainted sartan products came last summer after a U.S. drug manufacturer found NDMA at a high level in the API for valsartan that it got from a Chinese supplier. Since then, the FDA discovered that NDMA, NMBA and NDEA, all which are considered unsafe at certain levels, can be created during certain manufacturing situations for sartan drugs, including the reuse of solvents.
The surprise findings set off global recalls of hundreds of lots of valsartan, irbesartan and losartan and an intensive FDA investigation into how it could have happened and the dangers it poses to U.S. consumers. In the meantime, shortages have developed. The FDA this month approved a new impurity-free generic, Diovan, to help relieve shortages flowing from massive recalls.