Operator Error

Copy and waste

"We had several copies of the enterprise resource planning system in use during its validation, including the test (sandbox) copy, the quality (testing) copy, and the production copy," explains our GMP Agent-in-Place. "Some tests had to be done with the quality copy and others with the production copy.

"Needless to say, we made mistakes during this process. When we discovered these errors, we fixed them by re-running the tests on the correct copy. It was only during an after-the-fact audit by a consultant that we discovered we hadn't made any attempt to determine whether other tests had been done using the incorrect copies, and that we hadn't instituted preventive actions to assure it wouldn't happen again. We're still working on this."

Some mixing required

"We had a dermatological product that was emulsified, but we hadn't standardized the manufacturing process yet," says our GMP Agent-in-Place. "In fact, the mixing time depended on the equipment operator, who apparently ran the machine until the mixture 'looked' well mixed. We received numerous complaints for a particular batch that was filled into sample-size tubes. One complaint was that the emulsion was separating and a clear oily material could be seen.

"Our investigation found the same issue in our reserve samples. Although there was no patient danger, subsequent testing determined that the oily portion held no active, and the remaining product exceeded the specification for the strength of the active. This also indicated nonuniformity of the product in the tube. We recalled the batch and assembled 7000 recall packets. We also made the batch record more specific and validated the mixing times."

Heavy metal banned

"We had an injection product that had too many vials rejected during visual inspection of the batches, in some cases as many as 40%," notes our GMP Agent-in-Place. "An investigation showed that certain metallic precipitates were the source of the problem. These metallic precipitates formed when a metal-containing compound used by the stopper manufacturer as a mold-release agent reacted with the active ingredients. This mold-release agent was hand applied 'sometimes' by the supplier so it was an intermittent problem.

"We ended up rejecting the batches with abnormally high visual inspection reject rates, because the inspection would likely miss many vials with particulates. Eventually, we used a new stopper from a different manufacturer that did not use mold-release agents.

Double trouble

"We needed lyophilization capacity," says our GMP Agent-in-Place. "But instead of ordering a new lyophilizer, our engineering director agreed with a vendor who said we only needed a new chamber. The new chamber would share the condenser with the existing lyophilizer. Because the chambers would be linked, our vendor assured us, we could double the batch size and save money on samples and monitoring.

"After more than two years of installation and testing, we still hadn't filed the necessary new drug application amendments with FDA. By the time we did, we had spent as much money and time as we would have needed for installing and validating a new unit. Finally, the plant manager threw his hands up and halted the resource drain, and the old lyophilizer was used as a single stand-alone unit with the connection closed. What a waste."

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 AgentinPlace@advanstar.com We won't use any names, but if we do use your tale of disaster, courage, or just plain weirdness, Control will send you a coveted Pharmaceutical Technology t-shirt.