Serbian pharmaceutical manufacturer receives FDA warning

For failures in procedures during aseptic processing

Hemofarm, a pharmaceutical manufacturer based in Vrsac, Serbia, has received a warning letter from the US FDA after inspectors identified cGMP violations at its manufacturing plant.

An inspection carried out between 14–22 November 2011 found that the firm’s environmental monitoring data was not reliable, which ‘fundamentally compromised’ its ability to detect microbial contamination during aseptic processing.

According to the FDA, Hemofarm used dried/desiccated media agar plates for environmental monitoring testing. On 15 November 2011, the firm documented that 155 out of a total of 247 media plates evaluated were dried.

The FDA said the use of dried agar plates, which do not reliably support microbial growth, to recover microbial contamination is inadequate.

According to the inspectors, the firm’s environmental sampling and testing programme procedure was also inadequate because it failed to identify adequately (e.g. with diagrams) the locations from which the surface samples were collected. In addition, the firm did not collect sufficient active viable air samples and dynamic non-viable particulate air samples from the critical area during manufacturing.

The firm’s bioburden testing of the components also lacked adequate controls to ensure that the melted agar was sufficiently cool to prevent cell death of viable microorganisms.

Although Hemofarm had completed a study to determine the time required for the agar media to cool to the temperature of the water bath, the FDA said it was not adequate because it did not describe the study method, laboratory controls used for temperature monitoring, and time controls during this study.

Hemofarm was also criticised for failing to conduct adequate investigations of three media fill failures in the aseptic filling line used to produce sterile products.

The FDA said the firm did not have adequate written procedures for production and process controls to assure that the drug products it manufactures have the identity, strength, quality, and purity they purport to possess.

Until the firm’s manufacturing practices are verified to comply with cGMPs, the FDA said Hemofarm would remain under FDA Import Alert, and all articles manufactured at the Vrsac plant would be refused entry into the US.

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