FDA warning letter asks Merck KGaA to investigate all its sites

15-Feb-2012 - Last updated on 15-Feb-2012 at 10:30 GMT

The US FDA expects Merck KGaA to do a “comprehensive and global assessment” of its sites after sending a warning letter to three plants.

In the warning letter the US Food and Drug Administration (FDA) details quality shortcomings at sites in Switzerland and Italy. After finding the same failings at multiple sites the FDA expects Merck to look at all its operations.

“FDA expects Merck KGaA to undertake a comprehensive and global assessment of your manufacturing operations in all your facilities to ensure global, adequate, and timely resolution of the issues, including making needed improvements to your quality system”, the Agency wrote.

Most of the warning letter, dated December but published this week, focuses on a Merck Serono finished dosage form manufacturing facility in Aubonne, Switzerland that failed to properly investigate bent needles.

“Your investigation failed to assess whether the 75 complaints received between January 2009 and August 2010 represented a serious defect in your product”, the FDA wrote after inspectors visited the plant in June.

In December 2008 the syringe supplier notified Merck that 18 lots were produced with the wrong specifications and had a bent needle defect. Merck failed to evaluate the lots or take corrective actions, the FDA wrote.

“The defective syringes were used for the production of pre-filled syringes, completed at your facility, and therefore you are responsible for the quality of the materials received and used during the operation”, the FDA wrote. The Agency also raised concerns about complaints handling at the site.

Last month the FDA criticised the handling of consumer complaints at a Novartis facility in Nebraska. The 483 said Novartis was overdue with investigations into 1,360 consumer complaints linked to products manufactured at the plant.

Aubonne issues

Failure to properly investigate complaints was one of five concerns listed by the FDA. Other problems found by inspectors at Aubonne include inadequate reference standards, failure to tell the FDA about changes to production processes, and media fill shortcomings.

“The media fill programme does not include all major contamination risk factors in your aseptic process and consequently does not sufficiently demonstrate the state of process control”, the FDA wrote after inspectors visited the plant in June.

Some staff involved in aseptic manufacturing and filling of sterile drug products are yet to take part in a media fill, the FDA wrote, despite it being ‘essential’ for Merck to involve these employees in the process.

Merck implemented corrective actions, such as specific instructions for aseptic area operations, but the FDA deemed these inadequate. The FDA wants Merck to work on a risk assessment for previously manufactured products and an interim plan for production on ‘an appropriately qualified line’.

The FDA also found problems at Merck Serono sites in Fenil-sur-Corsier, Switzerland and Rome, Italy. At the Swiss plant Merck manufactures APIs (active pharmaceutical ingredients). Like at Aubonne, the plant failed to tell the FDA about manufacturing changes in a supplementary or annual report.