Many folks outside of this industry don’t realize that the FDA sends inspectors to drug manufacturing facilities in other countries. That might sound a bit odd, but agreeing to such inspections is in fact a condition of being able to sell pharmaceutical substances in the US (or to supply other companies that do). It’s a big job, and one feels sure that there are things that slip through the many possible cracks in the system – but still, it is good to see inspection reports like this once in a while that let you know that the system is catching clowns like this bunch (a facility in Gujarat state, India):
On October 24, 2018, our investigator observed torn documents of stability study data, analytical testing sheets, analysis calculations, and release forms that were placed into clear trash bags. Stability study documents for three batches of (b)(4) mg tablets were salvaged from the trash and compared to the official and approved records. Out-of-specification (OOS) results were among the data found, however the official results were recorded as within specification. Additionally, it was observed that blank stability study forms were prepared, pre-signed, and approved by the quality unit before recording the test data.
Um. That is not how you’re supposed to do QC. Heck, that’s not even how you’re supposed to cheat. Clear trash bags full of torn-up evidence of doctored stability studies? That you didn’t even bother to finish throwing away? Pre-signed, pre-approved forms waiting for someone to fill in the numbers? Never fear, though, there is always a good explanation for such behavior:
In your response, you acknowledged the multiple trash bags containing torn quality control documents and the practice of signing documents before recording the data. You stated the torn documents were from scale-up batches in which you tore the documents so as “not to create confusion in the mind of the investigator.” Your response was inadequate. . .
Just a bit. How people get things like that out with a straight face is always a mystery to me; I’d think anyone with a sense of the ridiculous would find it betraying them at that point. The letter goes on to detail numerous other violations – such as the computers for the HPLC systems used for purity analysis sharing the same user name and password between the QC technicians and company executives, with that set to a high enough level that data could be deleted or modified. And that’s not the only piece of hardware with problems:
. . .our investigator observed (an apparatus) identified as “cleaned.” However, this. . .was found to have visible product build-up. . .Furthermore, the air filter of the equipment was damaged with multiple holes. This equipment was used to manufacture finished drug products shipped to the United States . . . Additionally, a memo provided during the inspection stated these cleaning and equipment maintenance deficiencies were because of a shortage in manpower related to a nine-day dancing festival and government holiday.
“Sorry we couldn’t clean the last drugs off the machinery; too many people were out at the dancing festival” is not an excuse that gets you very far. But hey, I’m sure everything was perfectly clean before the holiday, right? Hardly anything caked on at all. This place was apparently run under a sort of Screwtape Letters version of Good Manufacturing Practices (perhaps AMP, for “appalling”?) The company’s products have been declared adulterated under FDA regulations, you will be glad to hear, and are being refused entry into the US. The letter provides a road map to what they would need to do to get back into compliance, but needless to say it is a list longer than an NBA center’s leg. And even if they try to provide all this documentation, another comprehensive inspection is also very much in order. I know, it shows my suspicious nature to doubt the word of people who tore up all the out-of-spec analysis forms and stuffed them into trash bags before the last visit. It’s a hard business.
Note: Here’s a previous post on such inspections, which contained some pretty spectacular behavior as well, but there’s always more where that came from.. . .