FDA Issues CRL for Ketamine to Treat Pain, Mental Health, and More

The US Food and Drug Administration (FDA) issued a complete response letter (CRL) on October 22, 2024, for the ketamine (KETARX) Abbreviated New Drug Application to treat anesthesia, sedation, pain, mental health, and neurological indications.¹

The CRL for PharmaTher’s application followed a previous one on April 18, 2024, with the FDA once again pointing out deficiencies.²

“The deficiencies cited in the CRL are classified as MINOR,” PharmaTher wrote in a statement.¹ “The FDA requested new and updated information and clarifications related to drug substance, drug product, manufacturing, and microbiology.”

The CRL hinders the progress of making ketamine more widely available in the US. Ketamine, approved for anesthesia and analgesia, has been in short supply since February 2018, according to the FDA’s list of scarce drugs.³

The short supply of ketamine has led people to seek out compounded ketamine products. Patients have turned to compounded ketamine for mental health, even though it is not approved for that indication in the US.

Back on October 10, 2023, the FDA published a compounding risk alert on October 10, 2023, stating the potential risks linked to compounded ketamine products for psychiatric disorders. The risks were discovered among patients receiving in-home compounded ketamine, unapproved by the FDA, via telehealth providers. However, a 2023 study assessing the real-world effectiveness of ketamine intravenous therapy showed significant improvement in depression, anxiety, and suicidal ideation.⁴

In the press release, PharmaTher said the FDA did not express concern about the stability of ketamine submission batches, which have demonstrated stability for 18 months.¹ The FDA also did not request any new trials.

“As noted by the FDA in the CRL, the resubmission to this CRL will be considered to represent a MINOR AMENDMENT, given that the deficiencies have been classified as MINOR,” PharmaTher wrote. “The Company will be working with its third-party manufacturing partner to resolve these deficiencies and respond to the FDA in a timely fashion.”

References

1. ^{PharmaTher Receives Complete Response Letter from the U.S. Food and Drug Administration for Ketamine Abbreviated New Drug Application. PharmaTher. October 23, 2024. https://www.globenewswire.com/en/news-release/2024/10/23/2967717/0/en/PharmaTher-Receives-Complete-Response-Letter-from-the-U-S-Food-and-Drug-Administration-for-Ketamine-Abbreviated-New-Drug-Application.html. Accessed October 23, 2024.}
2. ^{Derman, C. FDA Issues a CRL for Ketamine’s Abbreviated New Drug Application. HCPLive. April 29, 2024. https://www.hcplive.com/view/fda-issues-a-crl-for-ketamine-s-abbreviated-new-drug-application. Accessed October 23, 2024.}
3. ^{PharmaTher Announces Update on FDA New Drug Application for Ketamine. PharmaTher. September 4, 2024. https://www.pharmather.com/news/pharmather-announces-update-on-fda-new-drug-application-for-ketamine. Accessed October 23, 2024.}
4. ^{Hietamies TM, McInnes LA, Klise AJ, et al. The effects of ketamine on symptoms of depression and anxiety in real-world care settings: A retrospective controlled analysis. J Affect Disord. 2023;335:484-492. doi:10.1016/j.jad.2023.04.141}