FDA CRL - Armstrong Pharmaceuticals, Inc.

The Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Armstrong Pharmaceuticals for its New Drug Application (NDA 205920) concerning Epinephrine HFA Inhalation Aerosol 125 mcg/actuation. The FDA determined the application cannot be approved in its present form due to significant deficiencies across product quality, nonclinical, and clinical aspects. A recent inspection of the manufacturing facility revealed unresolved Current Good Manufacturing Practices (cGMP) violations. Nonclinically, the excipient thymol lacks adequate safety data for chronic oral inhalation, requiring further information or a 6-month toxicity study.

The most substantial concerns relate to the product's proposed over-the-counter (OTC) use for mild intermittent asthma. Clinical trials showed frequent device malfunctions attributed to user error, and behavioral and label comprehension studies indicated consumers, especially those with low literacy, had significant difficulty understanding and correctly performing critical steps such as priming, cleaning, and reassembly. The FDA emphasized that these usability issues are critical for an OTC product used without professional oversight. Required actions include resolving cGMP deficiencies, providing thymol safety data, revising the product labeling for improved comprehension, conducting new behavioral (human factors) studies with the actual product and diverse consumer groups, and performing a randomized actual-use study to quantify user errors, including a benchmark product. A comprehensive safety update is also required.