Issued November 13, 2025
Issued
November 13, 2025
Application
Other
Review center
Other
Stage
Final Decision
Letter type
Approval Letter
This document comprises two FDA Complete Response Letters (CRLs) issued to Laboratorios Farmacéuticos ROVI, S.A. for their New Drug Application (NDA) 214835 for Risvan (risperidone ISM) intramuscular injectable suspension. The letters state that the application cannot be approved in its current form due to various deficiencies related to facility inspections, product quality, human factors, and prescribing information.
The New Drug Application for Risvan was not approved due to critical unresolved manufacturing facility deficiencies, an inadequate Drug Master File, significant human factors concerns regarding product administration, and multiple outstanding requirements for clinical safety data presentation, analysis, and global experience, as well as administrative deficiencies related to foreign labeling translations.
Satisfactory resolution of deficiencies identified during pre-approval inspections of the manufacturing facilities is required before this application may be approved. Deficiencies were conveyed to the facility representatives.
Recommended response: Address all outstanding deficiencies identified during the pre-approval inspections of the manufacturing facilities and provide evidence of satisfactory resolution.
The referenced Drug Master File was found inadequate to support the submission. Deficiencies were sent to the DMF holder, and these must be adequately addressed before the application can be approved. The response should include the date the DMF holder amended their DMF.
Recommended response: Ensure the referenced DMF holder addresses all deficiencies and provide documentation of the amended DMF to the FDA.
The Instructions for Use (IFU) identified a vulnerability that may lead to medication errors, specifically difficulty injecting the full dose due to medication viscosity. The IFU needs revision to explicitly instruct users to inject the medication slowly and steadily.
Recommended response: Revise the Instructions for Use (IFU) to explicitly instruct users to inject the medication slowly and steadily, addressing the viscosity issue and potential for medication errors identified in human factors studies.
The application requires comprehensive re-presentation and analysis of clinical safety data. This includes presenting new safety data in a consistent format, combining original and new data, providing comparative tables for adverse event frequencies across all indications, retabulating reasons for premature trial discontinuations, describing changes in common adverse event incidence, and providing updated exposure information for clinical studies.
Recommended response: Re-analyze and re-present all clinical safety data, including new study data, in a consistent and comparative format, addressing adverse event frequencies, trial discontinuations, and exposure information across all indications.
Case report forms and narrative summaries are required for each subject who died during a clinical trial or who did not complete a trial due to an adverse event. Additionally, narrative summaries for all serious adverse events are needed.
Recommended response: Submit all requested case report forms and narrative summaries for subjects who died or discontinued due to adverse events, and for all serious adverse events.
A comprehensive summary of worldwide experience on the safety of this product is required, including an updated estimate of use for the product marketed in other countries.
Recommended response: Compile and submit a comprehensive summary of worldwide safety experience for the product, including updated estimates of use in other markets.
English translations of all current approved foreign labeling not previously submitted are required.
Recommended response: Submit English translations for all current approved foreign labeling that has not yet been provided to the agency.
The application faces significant hurdles to approval, primarily stemming from critical manufacturing and quality control issues (facility inspections, DMF inadequacy), a human factors design flaw impacting safe administration, and substantial gaps in the presentation and completeness of clinical safety data, including global experience and detailed case documentation.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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