FDA Warns Chinese Ingredients Maker About ‘Basic’ Manufacturing Problems

 Jan 5, 2015 
FDA commissioner Margaret Hamburg during a 2010 visit to Shanghai Not a Happee Chappee



 As if to illustrate why the FDA wants more inspectors in China, the agency recently issued a warning letter to a supplier of active pharmaceutical ingredients based in the industrial city of Wuxi that committed several fundamental manufacturing violations.

Notably, during an inspection last October, FDA inspectors found that employees at the Novacyl Wuxi Pharmaceutical facility failed to keep supporting raw data to verify that products met specifications. In its December 19, 2014, warning letter, the agency described this as a “basic responsibility.”

As an example, the inspectors found that changes were made to an impurities test without documentation or justification. Instead, employees relied on handwritten notes on a chromatogram that was “discovered in a drawer.” Moreover, there was no audit trail to trace who made the changes or when.

We asked Novacap, the parent company which is based in France, for comment and will update you accordingly. The FDA letter, by the way, does not mention which products or ingredients are made at the facility, although the Novacyl website indicates that acetaminophen is manufactured there.

There were other issues that led the FDA to question the quality of products made there. Novacyl failed to properly document or investigate discrepancies, establish appropriate lab controls or record good manufacturing practices which, the FDA noted, raised the likelihood that erroneous data would be recorded.

The agency cited one episode in which an analytical worksheet contained drug sample information but raw data was not properly linked to sample preparations. However, the company explained to the FDA that an analyst remembered the order in which the samples were prepared and placed into a test tube rack. This concerned the FDA.

“We are concerned that you rely on the memory of your employees,” the agency wrote, “rather than on actual supporting documentation. A basic principle of [good manufacturing practices] is to record activities at the time of performance to ensure that complicated activities and critical steps are performed according to written procedures.”

Pharmaceutical production in China is of increasing concern as companies there make a growing number of products or ingredients that find their way into the U.S. supply chain. The FDA opened an office in China in 2008 after a recall of the heparin blood thinner, which was made with a fake Chinese active ingredient and was linked to 246 deaths in the U.S.
The FDA wants to station more inspectors in China but has been stymied for more than a year, because the Chinese government has not issued enough visas. Since November, however, the agency signed two agreements with China(here is one and here is the other) that were linked to an agreement reached in late 2013 to expand FDA activities there.

“The December 2013 agreement did not link the issuance of visas with the completion of these documents,” an FDA spokeswoman writes us. “Operationally, however, the Chinese government in early 2014 linked these two commitments. With both documents now signed, we anticipate that the Chinese government will issue the relevant visas in the coming weeks.”

The agency would like to increase the number of U.S. inspectors to 26 from eight. Ten of the new hires would be assigned to inspect pharmaceutical plants, while seven would be assigned to inspect food producers. The last hire would be a managerial person.