The next PDUFA is not a done deal, but the notion that additional funding will be made available for the FDA to inspect manufacturing facilities near and far increasingly sounds like a good idea. Consider the latest development in China, where many pharmaceutical ingredients are made and have caused anxiety about the global supply chain. The State Food and Drug Administration there has found that 254 pharmaceutical companies, or 12.7 percent of all capsule makers, turned out unsafe capsules in a recent month-long inspection.
Of the 11,561 batches of drugs tested, 5.8 percent were found to contain excessive levels of chromium, according to the SFDA, which began the inspections after the Chinese media exposed that companies were making such capsules, according to the Xinhua news agency. Consequently, the SFDA ordered substandard drugs to be taken off shelves immediately. Authorities have so far investigated 236 capsule makers and ordered 42 to halt production, closed down 84 production lines, revoked production licenses of seven companies and referred 13 to the police.
Last month, media reports named several Chinese pharmaceutical companies that made capsules from industrial gelatin derived from scraps of leather material, which contains a greater amount of chromium than edible gelatin. Chromium, you may recall, can be toxic and carcinogenic if ingested in large amounts. As many as 13 commonly-prescribed drugs had been packed into capsules made with industrial gelatin containing a much greater amount of chromium than edible gelatin.
It is not entirely clear whether the capsules were distributed for local consumption only. Just the same, the episode underscores the larger concern that some Chinese companies that are intertwined in the pharmaceutical suppy chain operate as if China is a modern-day version of the Wild West. For instance, the health ministry there had reportedly banned the use of leather scraps in edible gelatin manufacturing seven years ago. But oversight was lacking until media reports highlighted the capsule problem.
In the aftermath of the heparin scandal, FDA commish Margaret Hamburg went on record as saying that she is encouraged by agency interactions with her Chinese counterparts (see here). Such infractions, however, cannot be considered too encouraging today. How far those extra PDUFA funds will ameliorate concerns remains to be seen. Meanwhile, watch your chromium levels.
9 Comments
And the supposedly USP or food grade gelatin went everywhere. Its consumption was not by any means limited to China.
When we inspected a series of gelatin capsule manufacturers in China a couple of years ago, each and every one of them lacked any sort of real QC or QA establishment, so there was no way for any of them to really know how much chromium or other profile contaminants were present in any given batch.
Even though the law against using scrap leather from shoe factories was in force, nobody was following the rule. Gelatin was simply gelatin. When we asked bulk gelatin suppliers what separate procedures were in place to segregate industrial from pharmaceutical grade material, the answer invariably was "None. The only thing different is the labeling on the drums we export and the way we print the CoA's."
I think the reason why they have not switched to non-gelatin capsules is that there are few reliable suppliers in China, and that the SFDA does not seemed to have mandated the switch.
For most Chinese, the larger issue is not just drugs, but food safety as well, as gelatin goes into a lot of things people eat.
"The Upper Middle Classes in China do not fully trust their own manufacturing processes when it comes to digestable products for human and animal consumption."