Inadequate Clinical Efficacy and Safety for Proposed Dosing
Severity: criticalMeloxicam Injection exhibits a delayed onset of action (2-3 hours) and waning analgesic effect (after 18 hours), rendering it unsuitable as monotherapy for acute pain and questionable for multimodal therapy at a 24-hour dosing interval. The proposal to label based on pharmacokinetic modeling for a shorter dosing interval is not supported by efficacy data and introduces additional safety risks due to predicted higher meloxicam levels. The available safety data are insufficient to support these higher meloxicam levels, as adverse events are dose- and exposure-related.
Recommended response: Conduct further clinical trials to demonstrate adequate efficacy and safety for the proposed indication and dosing regimen, or revise the proposed indication/dosing to align with the observed clinical profile. Provide robust data to support any pharmacokinetic modeling for dosing changes.
Prescribing Information Inadequate
Severity: minorComments on the proposed labeling are reserved until the application is otherwise adequate. The applicant is encouraged to review PLR Requirements for Prescribing Information, Pregnancy and Lactation Labeling Final Rule, and the Selected Requirements for Prescribing Information (SRPI) checklist. The response must include updated content of labeling in Structured Product Labeling (SPL) format.
Recommended response: Revise prescribing information according to PLR requirements, Pregnancy and Lactation Labeling Final Rule, and SRPI checklist. Submit updated content in SPL format upon resubmission.
Cited: 21 CFR 314.50(l)(1)(i)
Carton and Container Labeling Deficiencies
Severity: majorContainer Label: Add the lot number in accordance with 21 CFR 201.10(i)(1) and the expiration date in accordance with 21 CFR 201.17 and 21 CFR 211.137, using the recommended YYYY-MM-DD or YYYY-MMM-DD format. Carton Labeling-Single Vial: Review the draft guidance on product identifiers required under the Drug Supply Chain Security Act (DSCSA) to determine applicability to the product's labeling.
Recommended response: Update container and carton labeling to include the lot number and expiration date in the specified format. Review and comply with DSCSA product identifier requirements.
Cited: 21 CFR 201.10(i)(1), 21 CFR 201.17, 21 CFR 211.137
Proprietary Name Resubmission Required
Severity: infoThe proposed proprietary name, ANJESO, was found acceptable pending approval of the application in the current review cycle. It must be resubmitted when responding to the application deficiencies.
Recommended response: Resubmit the proposed proprietary name, ANJESO, with the complete response.
Comprehensive Safety Update Required
Severity: majorA comprehensive safety update, as described at 21 CFR 314.50(d)(5)(vi)(b), must be included with the response to deficiencies. This update should cover significant changes/findings in the safety profile, new safety data from studies/trials (presented in specific formats), retabulation of reasons for premature trial discontinuation, case reports/narrative summaries for deaths/serious adverse events, information on changes in common adverse events, updated exposure information, worldwide safety experience, and English translations of foreign labeling.
Recommended response: Prepare and submit a comprehensive safety update as per 21 CFR 314.50(d)(5)(vi)(b), incorporating all new nonclinical and clinical safety data, worldwide experience, and updated exposure information.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
