FDA 483 - Aptar Radolfzell Gmbh - February 25, 2022

A recent FDA inspection of Aptar Radolfzell GmbH, a sterile drug container closure manufacturer located in Eigeltingen, Germany, was conducted from February 21-25, 2022. The inspection resulted in an FDA 483 document detailing significant observations related to the firm's adherence to current Good Manufacturing Practices (CGMP).

The primary issues identified fell into three categories. First, the company failed to thoroughly investigate unexplained discrepancies and batch failures. This included a lack of investigation into increased scrap rates during manufacturing of Ophthalmic Squeeze Dispensers (OSD), failure to assess the impact of defective applicators used in multiple OSD batches, and inadequate investigations into microbiological contamination complaints, often dismissing them without full evaluation.

Second, the firm lacked written procedures for production and process controls to ensure drug product quality, specifically failing to conduct transportation studies for OSD packaging configurations destined for the US market.

Third, design verification processes were found insufficient, as design outputs did not consistently meet input requirements. Observations included an unjustified specification limit for the OSD vacuum tightness test, and flaws in the "Closure and Ventilation Integrity Study," such as inappropriate media selection, lack of review for contract lab protocols, and an inadequate study design that failed to consider critical functional criteria or verify long-term ventilation for multidose medications. Additionally, the Bacterial Integrity Filter Study used an unjustified liquid media for a hydrophobic air filter.

In response to these observations, Aptar Radolfzell GmbH is expected to implement comprehensive corrective and preventive actions to address the identified deficiencies and ensure compliance with FDA CGMP regulations for sterile drug container closure manufacturing.