Written By: Kalyani Boharapi, M. Pharm (RA)
Reviewed By: Pharmacally Editorial Team
NRx Pharmaceuticals announced on October 30, 2026, that the U.S. Food and Drug Administration (FDA) had approved its Abbreviated New Drug Application (ANDA) for Preservative-Free Ketamine. The approval came ahead of the agency’s November 10, 2026, Generic Drug User Fee Amendments (GDUFA) goal date.
The product is an American-manufactured ketamine injection formulation that excludes benzethonium chloride (BZT), an antimicrobial preservative used in existing ketamine injection products. The approval provides an alternative formulation without BZT while adding a new domestic source of sterile injectable ketamine.
Preservative-Free Formulation Addresses BZT Concerns
Ketamine injection products have traditionally contained BZT, which was incorporated into the original formulation developed in 1970. The preservative was previously considered necessary to maintain the drug’s long-term stability and sterility.
NRx developed a formulation that eliminates BZT while maintaining a sterile injectable presentation. The company highlighted regulatory and toxicological concerns surrounding the preservative, noting that the FDA has declined to designate BZT as Generally Recognized as Safe (GRAS).
Under current FDA policy, BZT is restricted in several product categories, including new drugs, consumer hand cleansers, wipes, and healthcare and surgical hand rubs. Its inclusion in intravenous formulations is also subject to concentration thresholds.
NRx has filed a Citizen Petition with the FDA seeking the removal of BZT from ketamine formulations. An expert toxicology report referenced in the company’s announcement indicates that patients receiving ketamine at routinely used doses for labeled indications may be exposed to BZT levels exceeding the published FDA maximum daily exposure of 1 mg.
These findings represent the company’s cited toxicological rationale for removing the preservative. The October 30 announcement does not report comparative clinical safety outcomes between preservative-containing and preservative-free ketamine.
US Manufacturing and Commercial Supply Readiness
NRx is manufacturing Preservative-Free Ketamine in collaboration with Nephron Pharmaceuticals in West Columbia, South Carolina. The manufacturing process uses blow-fill-seal technology, which integrates container formation, filling and sealing into a manufacturing process designed for sterile injectable products.
The approval comes amid an ongoing shortage of traditional ketamine injection products. According to NRx, ketamine injection has remained in short supply since 2018 and continues to appear on the FDA drug shortage list, with some manufacturers having discontinued production.
NRx reported that commercial supply had already been manufactured and was on hand before approval. The company can now proceed with product labelling and supply to hospitals and clinics.
Ketamine is primarily used in hospital settings for anesthesia and pain management, including labor and delivery. Additional domestic manufacturing capacity could provide hospitals with another source of supply for these established clinical applications.
NRX-100 and NRX-101 Development Programmes
Alongside its commercial ketamine programme, NRx continues to advance two separate development candidates targeting psychiatric conditions.
NRX-100 is an intravenous ketamine presentation for which the company is pursuing a New Drug Application (NDA) with proposed claims for depression and suicidality. The programme has received FDA Fast Track Designation for suicidal ideation in depression, including bipolar depression.
NRX-101, an oral combination of D-cycloserine and lurasidone, has received FDA Breakthrough Therapy Designation for suicidal bipolar depression.
In October 2026, the Defense Advanced Research Projects Agency (DARPA) awarded NRx an $11.25 million contract to conduct a Phase 3 trial evaluating NRX-101 in combination with robotic neuronavigated transcranial magnetic stimulation. The programme will investigate the combination as a one-day treatment approach for patients with depression.
The NRX-100 and NRX-101 programmes remain distinct from the newly approved preservative-free ketamine ANDA.
Regulatory and Manufacturing Significance
FDA approval provides NRx with a preservative-free ketamine formulation supported by domestic manufacturing and commercial supply already on hand. The development addresses a formulation concern involving BZT while potentially expanding supply options in a market affected by persistent ketamine injection shortages.
The manufacturing collaboration with Nephron Pharmaceuticals also demonstrates the company’s approach to producing sterile injectable medicines in the United States using blow-fill-seal technology.
However, the approval represents a regulatory and manufacturing milestone rather than a new clinical efficacy or safety finding. The announcement does not report clinical trial results demonstrating improved patient outcomes with preservative-free ketamine.
The next important development will be the commercial introduction of the approved product and its contribution to ketamine injection supply in the US market.
Reference
NRx Pharmaceuticals (Nasdaq:NRXP) Receives FDA Approval of Preservative-Free Ketamine Ahead of November 10 FDA Goal Date, NRx Pharmaceuticals, 30 October 2026
About the Writ
Kalyani Boharapi (LinkedIn) is a pharmacy professional and healthcare writer currently pursuing an M.Pharm in Regulatory Affairs at Dr. D. Y. Patil College of Pharmacy, with interests in pharmaceutical regulations, drug development, and healthcare innovation. She has academic exposure to dossier preparation, scientific writing, and regulatory documentation. Kalyani has also completed certification courses in Generative AI, AI in Pharma, and Bioinformatics, and actively participates in pharmaceutical conferences to stay updated with emerging trends and advancements in the healthcare and pharmaceutical industry.