FDA CRL - Amphastar Pharmaceuticals, Inc.

The FDA issued a Complete Response Letter (CRL) to Amphastar Pharmaceuticals, Inc. regarding its New Drug Application for Naloxone Nasal Spray, indicating that the application, filed under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, cannot be approved in its current form. Key issues identified include the product's user interface, which a human factors validation study found not to support safe and effective use for all intended users. Device performance specifications for spray characteristics, particularly the delivered amount, were inconsistent with provided information and require modification and retesting. The proposed reliability specification at expiry was deemed unacceptable for an emergency treatment product.

Significant safety concerns were raised about the potential for product run-off into the posterior pharynx, especially in the youngest pediatric patients, risking aspiration and inadequate naloxone absorption. The FDA requires either product reformulation or additional data to support use across all pediatric age ranges down to birth. Furthermore, a recent inspection of the International Medication Systems Limited manufacturing facility identified device-related deficiencies under 21 CFR 820, requiring satisfactory resolution before approval. Amphastar must also address unresolved labeling comments, resubmit its proposed proprietary name, and provide a comprehensive safety update. The company is required to fully address all deficiencies and resubmit the application within one year.