NRx Pharmaceuticals has announced that the US Food and Drug Administration (FDA) has approved the company’s Abbreviated New Drug Application (ANDA) for Preservative-Free Ketamine. The approval comes ahead of the FDA-announced November 10, approval goal date.

Jonathan Javitt, MD, MPH, Chairman and Chief Executive Officer, NRx Pharmaceuticals, said, “We are excited to bring Preservative-Free Ketamine to market and to give patients and their physicians an option for repeat treatments without the potential dangers of a preservative that has been classified as unacceptable for inclusion in multiple product categories by the US Food and Drug Administration.

“Ketamine injection has been in short supply since 2018 and currently appears on the FDA drug shortage list with some manufacturers discontinuing production. The Secretary of Health and FDA Commissioner have previously identified ketamine as a strategic drug whose supply in the US must be assured. With manufactured commercial supply on hand, we can now label our product and supply American hospitals and clinics. In those settings, ketamine is used primarily for anesthesia and pain control, including in labor and delivery, where it is the only IV anesthetic that minimises suppression of breathing in the baby. We are pleased to work with our partners at Nephron Pharmaceuticals in West Columbia, South Carolina, who have helped us prove that sterile, preservative-free injectables can be made in America,” he added.

Currently, all available ketamine injection products contain benzethonium chloride (BZT).

According to current regulation, inactive ingredients in drugs (including preservatives) must be Generally Recognised as Safe (GRAS) or proven not to be unsafe. The FDA has declined to designate Benzethonium Chloride as GRAS.

Under current FDA policy, benzethonium chloride cannot be included in new drugs, consumer hand cleansers, wipes, healthcare or surgical hand rubs nor in intravenous formulations above a threshold concentration for toxicological reasons.

Ketamine is one of the few remaining old drugs, initially formulated in 1970 to contain BZT. Prior to NRx’s novel formulation, it was widely believed that BZT was required for long-term stability and sterility of ketamine.

The company has filed a Citizen Petition with FDA seeking to have BZT removed from ketamine and an expert toxicology report is available to the public on the FDA docket. That report, compiled by a Board-Certified Toxicologist under the supervision of a regulatory law firm, documents that patients receiving ketamine at dosages routinely used in hospitals and clinics for labeled indications may be exposed to levels of BZT that exceed the published FDA maximum daily exposure of 1 milligram.