| Spravato |
A prescription‑grade, intranasal formulation of esketamine, the S‑enantiomer of ketamine. |
Approved in 2019 for treatment‑resistant depression (TRD) and for reducing suicidal ideation in adults with major depressive disorder (MDD). |
| 505(b)(2) designation |
A special FDA filing route that allows a drug applicant to rely on a combination of:
• data from the applicant’s own studies,
• data that were previously submitted to the FDA for another product (e.g., a generic or a drug that used the same active ingredient),
• published literature, or
• non‑clinical data from other sources. |
Spravato’s 505(b)(2) NDA used:
– clinical data generated by Janssen for the intranasal product,
– published data on the safety and pharmacology of ketamine and esketamine (including data that supported the earlier approval of esketamine for pain under a different formulation), and
– the FDA’s prior review of ketamine’s pharmacology. |
| Why choose 505(b)(2)? |
1. Faster time to market – you can piggy‑back on data already approved or published.
2. Reduced cost – you may avoid some of the pre‑clinical work that would be required for a wholly new drug.
3. Greater flexibility – you can add new indications, novel delivery methods, or dosage forms. |
For Spravato, the 505(b)(2) route let Janssen bring a nasal spray formulation to patients without having to redo the entire safety profile of esketamine. The FDA could review the new data for the new route, while still relying on the established pharmacology of the molecule itself. |
| Key regulatory milestones for Spravato |
• June 2017 – Janssen submits the 505(b)(2) NDA.
• May 2019 – FDA grants approval for the drug.
• 2019‑2020 – FDA approves additional labeling for suicidality.
• 2023 – Janssen adds a new dosage form (a 150 µg/30 µg combination spray). |
All of these were possible because the 505(b)(2) framework permitted a streamlined review that leveraged existing safety data on esketamine and ketamine. |
| What is the product’s current status? |
Spravato is available through a special delivery program (SPDP) that requires:
• a prescriber training program,
• monitoring of patients for dissociative effects,
• a secure dispensing and dispensing record. |
The SPDP is a key part of how the FDA ensures safe use, especially given the drug’s potential for dissociation and abuse. |
| How does the 505(b)(2) approach affect patients and prescribers? |
Because the drug’s safety profile was partially based on previously approved data, clinicians can rely on established information about esketamine’s side‑effect profile (e.g., dissociation, blood pressure changes). The new route of delivery (nasal spray) adds a new set of pharmacokinetic considerations—such as absorption and peak concentration—that the FDA reviewed. |
Spravato’s labeling and monitoring guidelines reflect both the old and new data, ensuring that prescribers are well‑informed about how the drug behaves when used intranasally. |