On Feb. 21, 2011, FDA posted a copy of a Warning Letter that was sent to the chairman of the executive board of Merck KGaA on Dec. 15, 2011, regarding cGMP violations identified at three of its European facilities: MS-Corsier-sur-Vevey, MS-Aubonne, and MS-Tiburtina. The letter was issued in response to inspections conducted between Jun. 27 and Jul. 1, 2011. Merck KGaA provided responses to the inspection reports in late June and July 2011 that FDA found to be insufficient.

At the MS-Corsier-sur-Vevey plant, which manufactures APIs, FDA found that changes to a product, production process, quality controls, equipment, or facilities were not reported to FDA. The company indicated in its response letter to FDA that the changes had no effect on the finished API, but in the Warning Letter, FDA asks the company to provide the scientific rationale behind that assertion.

At the MS-Aubonne plant, a finished drug-manufacturing facility, FDA found several violations of cGMP. They found that the company had not:

• Established or followed appropriate written procedures designed to prevent microbial contamination of drug products purporting to be sterile
• Established or followed appropriate written procedures for the handling of complaint records to determine if an investigation is required
• Established scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, in-process materials, and drug products conform to appropriate standards of identity, strength, quality, and purity
• Submitted a Biological Product Deviation Report (BDPR) to FDA
• Reported changes to a product, production process, quality controls, equipment, or facilities.

The MS-Tiburtina site is responsible for testing products destined for the United States. At the MS-Tiburtina, FDA found that Merck KGaA had not thoroughly investigated the failure of a batch or any of its components to meet its specifications whether or not the batch has already been distributed.

FDA notes in the Warning Letter that some of the cGMP violations listed in the letter impacted all three Merck KGaA facilities, and that “The lack of compliance with cGMPs may lead to production problems and adversely impact the availability of critical medically necessary products that meet required quality standards.”