For those wondering about potential problems with active pharmaceutical ingredient makers in China, consider the case of Ningbo Smart Pharmaceutical. The company was cited in March 30 warning letter from the FDA for various problems - alleging impurity testing was done when, in fact, it was not; failing to test all API lots shipped to customers and tossing all sorts of data that should have been kept.
In short, the FDA sent a letter that spells out not only the basic tenets of good manufacturing practice, but also some common sense rules for making and supplying APIs. On one hand, some might say the FDA was on the ball here, catching a supplier with some bad practices. On the other hand, who knows how many Ningbo APIs made their way into medicine chests? And what about any others?
As for Ningbo, the FDA points out one issue: the API supplier's quality unit failed to ensure that materials are approriately tested and results are reported. A certificate of analysis indicated organic volatile impurities levels conformed to specifications, but the inspection found no testing was done. "It is essential that your firm only report results to customers when you have actually performed the analysis," the FDA writes in reference to what may be called API Manufacturing 101.
Then there was a failure to perform at least one identity test of each batch of incoming material. The agency wants Ningbo to provide a copy of incoming raw material testing procedures and explain how Ningbo will assure all raw materials are tested prior to release for production in the future. Why was the verification requested? As it so happens, Ningbo destroyed documentation, which makes it hard to demonstrate released batches were tested and met specifications. And so, the FDA had this to say...
"Our inspection reported that your firm has destroyed some old, but foundational records for your products. We recommend that your firm reconsider your record retention policy for application-related records. Should product quality or safety concerns arise in the future, the original records pertaining to batches listed in an application may be integral in providing reasonable assurances to the Agency regarding a product and integrity of data submitted to support it.
"When destruction of documents is appropriate, you should follow a document destruction procedure that ensures documents are destroyed in a controlled manner. This would include, at a minimum, identification of the appropriate documents and retention timelines, documentation of what was destroyed, and the names and signatures of those who witnessed the destruction."
For now, though, the evidence has been destroyed (you can read the warning letter here).
5 Comments
Why has the FDA not shut down all U.S. operations with APIs sourced from Ningbo?
It seems clear to me that "the FDA was on the ball here." The last item cited in the letter makes it clear that some real work was involved because Ningbo Smart, as they say, "wasn't on the list."
"Additionally, your firm is neither registered nor has it listed every API in commercial distribution in the United States with FDA, as required by 21 C.F.R. § 207.40 and section 510(i) of the Act [21 U.S.C. § 360(i)]. The FDA investigators discussed this issue with you during the inspection. Your response did not address this issue. ......"
FDA inspected and cited a facility that administratively they weren't supposed to know about. This takes more effort than simply working through the list of registered facilities. Hopefully, it will not be the last such letter posted for firms in this status.
One more reason why every lot of materials used to manufacture a product are fully tested against specifications until vendor verification can be established.
Look for a lot more of this sort of thing happening.
Is it me, or is this an instance where the truth seems more frightening than fiction?