Regulatory Focus™ > News Articles > Sterility Violations Form Basis of FDA Warning Letter to Novo Nordisk

Sterility Violations Form Basis of FDA Warning Letter to Novo Nordisk

Posted 07 February 2013 | By Alexander Gaffney, RAC 

Life sciences manufacturer Novo Nordisk has been sent a Warning Letter from the US Food and Drug Administration for what regulators said were "significant" deficiencies found at the company's Bagsvaerd, Denmark facility.

FDA officials said they were particularly concerned about current good manufacturing practice (CGMP) violations found at the firm, which included practice deviations that could have potentially led to product being manufactured under non-sterile conditions. Nearly 900 environmental monitoring (EM) samples had not been collected from three areas that manufactured one of its sterile products, FDA noted, calling that number of missed samples "substantial" and suggestive of a larger, concerning "pattern" of violations.

"Collecting scheduled EM samples is a critical aspect of any environmental control program at an aseptic manufacturing facility," FDA explained. "Since 2010, [Novo Nordisk] Manufacturing and Quality Units were unable to implement effective corrective actions to ensure all of the EM samples are consistently collected."

Novo's response to FDA indicated that some of those missing samples may have been invalidated due to over-exposure, but FDA said that, too, raised questions as to why such problems had been ongoing since 2010.

Mounting Problems

A number of other sterility violations were also observed by FDA regulators during their inspection of the facility. Some operators, they said, were seen wearing goggles in an aseptic area that had "not been adequately sterilized and had two openings on the top." Those goggles had been sanitized-not sterilized-FDA said.

In another example, FDA said the company's environmental monitoring functions were performed too far away from the filling station on the aseptic fill line, making it less likely that it would be able to detect any non-viable particulate matter present in or around the sterile products.

In still other instances, FDA said the company had failed to investigate "impurity peaks" found in various products, though the company said those peaks were caused by other products manufactured on the same production line. FDA said the company did not provide data to substantiate this claim, and was similarly concerned that residues left on the manufacturing equipment could negatively affect subsequent products. Regulators asked for additional information regarding this latter point, including how the residue is cleaned from equipment and whether the company has acceptance criteria for when or if it is found in other products manufactured on the same line.

Regardless of the cause of the problems, FDA explained that they raised broader concerns about the company's ability to conduct corrective and preventive action (CAPA). "Additionally, we are concerned that no investigation was conducted until this situation was brought to your attention by our investigator."

"Until all corrections have been completed and FDA has confirmed corrections of the violations and your firm's compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug product manufacturer," the agency wrote in the letter.

FDA also called on the company to inform it if any actions taken to remedy the concerns noted in the warning letter could cause drug shortages. The US is already dealing with a rash of such shortages, including a large number of sterile injectable drugs-the very same type that comprises nearly the entirety of Novo's product line.

Regulatory Focus has reached out to Novo Nordisk and will update this space when we hear back. 


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