FDA Officials Highlight Compliance and Warning Letter Trends

September 15, 2017

CDER’s Office of Manufacturing Quality issued 45 warning letters through Sept. 1 of this year, not counting actions against compounders, according to Francis Godwin, a division director in OMQ.

Data integrity deviations ranked first on a list of recent trends, followed by issues related to the interplay of sponsors and contract manufacturing organizations. Newer trends included suspect supply chain information and weak controls in connection with risky cuts in manufacturing costs.

“If this trend continues, we’ll probably be over 60 warning letters by the end of the year,” Godwin said, in a presentation at the Joint Regulatory Conference of the FDA and the Parenteral Drug Association in Washington, D.C.

The OMQ also issued 25 import alerts, sent four untitled letters and held 21 regulatory meetings with companies this year, he said.

One trend the FDA has seen in its warning letters this year has been a lack of testing performed for toxic contamination. One firm failed to analyze a supplier’s glycerin for the presence of diethylene glycol — also known as antifreeze — which can be cheaper to manufacture and has been the cause of several lethal poisonings worldwide. Glycerin is used as a raw material in multiple drug products.

In addition, FDA guidance recommends validated testing for the contaminant oversulfated chondroitin sulfate, previously seen in Chinese-manufactured crude heparin shipments. The agency recently issued a warning letter to a contract testing lab for failing to establish a suitable OSCS testing system, Godwin said.

Small, overlooked problems can snowball into larger and more dangerous compliance issues, said CBER consumer safety officer Robert McElwain.

One company discovered a leak in an aseptic transfer tube, though the product passed all sterility testing. The firm did not contact CBER until after a lengthy internal investigation, ultimately deciding to reprocess the entire lot after hours of wasted time.

Another company discovered several final product sterility failures, as well as bulk sterility failure, including identifying a single organism in product testing and environmental monitoring. But the company’s management and quality unit described each failure as a separate incident and not part of a larger trend.

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