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Regulatory Focus™ > News Articles > FDA Sends Untitled Letter to Danish Drugmaker Over GMP Issues

FDA Sends Untitled Letter to Danish Drugmaker Over GMP Issues

Posted 25 July 2016 | By Michael Mezher 

FDA Sends Untitled Letter to Danish Drugmaker Over GMP Issues

The US Food and Drug Administration (FDA) has issued an untitled letter to Danish allergy immunotherapy company ALK-Abelló (ALK) over manufacturing and quality control issues at its Horsholm, Denmark facility.

The letter, dated 15 July 2016, comes after a 12-day inspection of the facility in March 2016, during which FDA investigators cited ALK for four "significant deviations" from current good manufacturing practice (cGMP) requirements. Additionally, FDA says that some of the observations listed in the letter are repeat deviations from a 2014 inspection of ALK's Fort Washington, NY, facility.

First, FDA says ALK failed to "establish and follow appropriate written procedures designed to prevent microbiological contamination."

Here, FDA says ALK failed to effectively monitor the water-for-injection (WFI) use points for Pharmalgen, a venom-based allergy immunotherapy product. "There is no procedure in place that specifically addresses the requirements and actions to be taken for use points with consecutive action level bioburden excursions," FDA writes.

According to FDA, there were roughly 80 bioburden excursions at the facility since the 2014 inspection, yet ALK did not initiate any corrective or preventative actions in January 2016.

Second, FDA says ALK failed to "routinely calibrate, inspect, or check automatic, mechanical, or electronic equipment according to a written program designed to assure proper performance." In one example, the agency says ALK had not requalified one of its lyophilizers for 16 years. According to the letter, the company had to abort numerous batches of Pharmalgen as a result of the lyophilizer malfunctioning.

Third, FDA says that ALK failed to establish and follow sufficient written procedures for testing its products. For example, FDA says the company failed to test 125 Pharmalgen, grass and ragweed samples at the appropriate time.

According to the letter, ALK's response to citations made in the Form 483 following the inspection were "insufficient" as the company failed to provide detail as to how it would update its written procedures and improve employee training.

As such, FDA says that "further information and discussion with [ALK] will be necessary to adequately review and assess [its] planned actions."

Furthermore, FDA specifically asks ALK to provide more information on the company's use of expired agar plates in its environmental monitoring of the facility, and requests "additional information on [its] actions to correct this issue and prevent recurrence."

ALK spokesman Jeppe Ilkjær told Focus his company is working to address the issues raised in the letter, saying, "ALK is in open dialogue with the FDA to resolve the issue and expects to submit additional formal responses very soon."


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