FDA 483 - Holopack Verpackungstechnik GmbH - February 18, 2020

An FDA inspection conducted from February 10-18, 2020, at Holopack Verpackungstechnik GmbH in Sulzbach-Laufen, Germany, identified significant observations regarding the company's compliance with manufacturing regulations. The inspection, documented in an FDA Form 483, highlighted three main issues. Firstly, the company's procedures for preventing microbiological contamination in sterile drug products were found to be deficient. Specifically, validation of the aseptic filling process lacked a complete smoke study to assess turbulent airflow in critical ISO 5 areas, and there was no written procedure with acceptance criteria for challenging alarm systems critical to maintaining the integrity of these zones. Secondly, routine calibration and performance checks for automatic and mechanical equipment were not consistently performed according to a defined written program. For instance, temperature probes used in a critical validation study exceeded their calibrated range, and equipment qualification was incomplete for a packaging line to ensure consistent sealing and accurate product weight verification at established speeds. Finally, laboratory controls for water sampling were deemed inadequate. The water sampling procedure for bioburden and objectionable organism testing was not representative of actual production use, as it included disinfection and flushing steps prior to sampling that were not reflected in the corresponding production batch records. These observations indicate a need for Holopack Verpackungstechnik GmbH to implement robust corrective and preventive actions to ensure compliance with good manufacturing practices and safeguard the quality and sterility of its drug products.