Issued January 1, 2023
Issued
January 1, 2023
Application
Other • 208969
Review center
Other
Stage
Final Decision
Letter type
Approval Letter
The FDA issued a Complete Response letter for Amphastar Pharmaceuticals, Inc.'s New Drug Application (NDA) 208969 for Naloxone Nasal Spray, indicating that the application cannot be approved in its present form due to several deficiencies. These include issues with the human factors validation study, pediatric safety concerns regarding product administration and absorption, unresolved manufacturing facility deficiencies, and the need for a comprehensive safety update. The letter provides recommendations for addressing these issues and outlines the process for resubmission or other actions.
The application was not approved due to inadequate human factors validation, significant pediatric safety and efficacy concerns (aspiration risk, absorption), unresolved manufacturing facility deficiencies, and pending proprietary name review.
Based on the results of the human factors (HF) validation study, the product user interface does not support a conclusion that all intended users can use this product safely and effectively.
Recommended response: Conduct additional human factors studies to demonstrate safe and effective use by all intended users, addressing identified user interface issues.
Administration of the proposed product has the potential to lead to run-off into the posterior pharynx, especially in the youngest pediatric patients, raising safety concerns surrounding respiratory complications due to aspiration and effectiveness concerns due to inadequate absorption of naloxone. The pediatric assessment does not adequately address these concerns to support use of the product down to birth. The application must support the use of the product in all age ranges, including children down to birth. Consider re-formulating your product for use in adults and pediatric patients down to birth.
Recommended response: Provide additional data to address pediatric safety and efficacy, particularly regarding aspiration risk and absorption. Consider product reformulation or alternative delivery methods suitable for all pediatric age groups, including neonates.
The review of your proposed proprietary name has been terminated due to the deficiencies with the application as described in this letter. Please resubmit the proposed proprietary name when you respond to the application deficiencies.
Recommended response: Resubmit the proposed proprietary name once all other application deficiencies have been adequately addressed.
During a recent inspection of the International Medication Systems Limited (FEI 2016148) manufacturing facility for this application, our field investigator conveyed device (21 CFR 820) deficiencies to the representative of the facility. Satisfactory resolution of these deficiencies is required before this application may be approved.
Recommended response: Address and resolve all deficiencies identified during the facility inspection at International Medication Systems Limited, providing documentation of satisfactory resolution.
Cited: 21 CFR 820
When responding to the deficiencies, include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b). The safety update should include data from all nonclinical and clinical studies/trials of the drug under consideration regardless of indication, dosage form, or dose level, detailing any significant changes or findings in the safety profile and presenting new safety data combined with original application data.
Recommended response: Prepare a comprehensive safety update as per 21 CFR 314.50(d)(5)(vi)(b), incorporating all new nonclinical and clinical safety data, and present it in the required format upon resubmission.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
Key themes include critical pediatric safety and efficacy gaps, insufficient human factors validation for safe use, and unresolved manufacturing quality system issues, all contributing to the non-approvability of the product.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
Document viewer
Read the FDA letter and send context to the co-pilot at any time.