A holey problem
"We were using the same butyl rubber stoppers that we had used for decades, even though stopper formulas and technology had advanced," says our GMP Agent-in-Place. "Finally, we decided we needed a better stopper and could reduce our reliance on one vendor by using an alternate supplier and a modern formula.
"We conducted the appropriate product studies, extractable studies, validation studies, stability studies, and test runs to ensure the stopper could be applied using our existing machinery and obtained FDA approval. We ordered the stoppers. A few months into the use of the new stoppers, the quality assurance inspector found a pencil-tip diameter hole in one sample stopper during inspection. Unfortunately, the inspector decided this wasn't a major defect, and because only one was found, it met the criteria for release."When the first customer complaint came and our investigation found the inspection report, we realized we had a critical issue and immediately recalled all affected batches. We concluded that the new vendor didn't have as much experience in stopper manufacture as the previous one and didn't have proper pressure regulators on the air used to eject the stopper in the molding and trimming process. Excess pressure was sufficient to blow a hole in some stoppers, which also had a newly designed, thinner, septum. That we had incoming QA inspectors who couldn't identify a critical defect was just ducky as well."
A smoky problem
"I worked in a European manufacturing facility," notes our GMP Agent-in-Place. "It was company policy to have a senior quality assurance employee from the US 'assist' us in hosting FDA inspections. This made sense because of potential language difficulties or trends in FDA inspections that we might not be aware of, and he likely had tremendous experience in handling FDA inspections.
"During this particular inspection, the US representative arrived around lunch time on Monday after having flown overnight from the US and then immediately joined the inspection that was in progress since 9 am. Unfortunately for him, we were watching videos of several aseptic-suite smoke studies in a darkened room. He fell asleep and started snoring, bringing a laugh to all of us (FDA included)!"
A fishy problem
"We make products that need refrigeration," explains our GMP Agent-in-Place. "For big orders, we arrange sole use of refrigerated trucks. For one such order, the truck came, but it smelled like its last load: fish. Of course we refused it. I have to wonder what the trucking company is thinking at a time like this."
A flakey problem
"During a six-month time period, the number of failing bioburden tests of floor samples in our clean manufacturing area was increasing," reports our GMP Agent-in-Place. "When we investigated the problem, it was clear the sealer in the floor was flaking and peeling off, including in areas that were environmental sampling sites.
"Because we weren't allowed to shut down the area for repairs, we compensated as best we could by tripling the floor disinfection frequency. Even so, we continued to get sporadic failures on those floor sites. The intermittent failures continued until we finally had to shut down and we could get the floor resurfaced. Luckily, the product bioburden levels never showed a corresponding increase."
Pharmaceutical Technology's monthly "Agent-in-Place" column distills true-life cautionary tales from the secret files of Control, a senior compliance officer. If you have a story of clueless operators, oblivious management, inopportune lapses of judgment, or Murphy's Law in action, please send it to Control at