FDA Inspections in the EU: Warning Letter to Italian OTC Drug Manufacturer

Despite the Mutual Recognition Agreement (MRA) between the EU and the FDA, which aims to minimize redundant inspections by recognizing each other's inspection outcomes, the FDA retains the authority to inspect EU-based facilities when necessary. This is evident from a recent Warning Letter issued to Originitalia SRL, an Italian manufacturer of over-the-counter (OTC) drug products.

The Warning Letter underscores the critical importance for EU-based manufacturers to maintain compliance with CGMP standards to avoid regulatory actions that could impact their ability to supply products to the U.S. market.

In May 2024, the FDA conducted an inspection of the company's facility in Caldogno, Italy, where several significant CGMP violations were identified, resulting in a Form FDA 483. As the FDA deemed the company’s response inadequate, due to the lack of supporting documentation and sufficient evidence of corrective actions, the FDA issued a Warning Letter on 07 November 2024.

The inspection revealed significant violations of Current Good Manufacturing Practice (CGMP) regulations, including:

• Failure to test incoming active pharmaceutical ingredients (APIs) for identity before manufacturing over-the-counter (OTC) drug products.
• Reliance on suppliers' certificates of analysis (COAs) without validating their reliability.
• Inadequate testing of finished drug products for identity and strength before release.
• Lack of established written procedures for production and process validation to ensure drug quality and purity.
• Inadequate stability data to demonstrate that the chemical and microbiological properties of the drug products met established specifications and remained acceptable throughout their shelf life.

As a result, the FDA placed the company’s products intended for import into the U.S. on Import Alert 66-40 ("Detention Without Physical Examination of Drugs From Firms Which Have Not Met Drug GMPs") as of 01 October 2024. The FDA has requested that Originitalia SRL take comprehensive corrective actions and provide supporting documentation to resolve the identified deficiencies. In response, the company announced  "the freezing of OTC production for the year 2024.'

For more details, refer to the Warning Letter to Originitalia SRL. on the FDA's Website.