"Did I tell you before that I hate complaints?" asked our GMP Agent-In-Place. "We would get complaints regarding the taste of our antihypertensive drug product. Our hypertensive senior manager for the area who took the subject antihypertensive product would do a taste test on the returned material. She would immediately spit it out so as not to overmedicate. I don't remember a case where she found the taste abnormal."
Mal-adjusted"It was a complicated process ending with a series of filtrations," our GMP Agent-In-Place began. "Because the material was expensive, we wanted to push all the product possible through the filters. We added a postwash step to the process to assure this. But the process change did not take into account the dilution of the final material. We danced on the edge of the specification for a year or two, as pointed out by an internal audit. However, because the product met specifications, nothing was done about it. The obvious happened, and several batches fell below specifications and had to be rejected. The corrective action was obvious: adjust the volumes for the postwash."
"We contracted out our rabbit pyrogens test to a contract laboratory," began our GMP Agent-In-Place. "When we had a series of pyrogen test failures on a product that normally has no pyrogen concerns, we naturally talked to the contract laboratory to see if they might have an explanation. Among other things, we asked if the lab made any changes. They noted they had changed from Chinchilla rabbits to New Zealand white rabbits; a change for which they had not previously notified us. While the change was not a concern, the lab then noted that during the time of the changeover, they had rabbit health problems in the animal farm (coccidia infections). Based on this information, we sent samples of the failing product batches, along with some passing product batches, to a new contract pyrogen testing laboratory. All batches passed with the usual zero-degree temperature rise in the rabbits. Based on this information and the investigation, we released the batches—and changed testing laboratories."
"During processing of our product, we use ethanol," our GMP Agent-In-Place explained. "On one particular day, the operators noted an 'off' odor. The quality staff looked at the raw-material release tests and the finished product tests, and found no unusual test results. The odor continued to occur after the addition of ethanol in the product, so it was thought that the ethanol was the cause. When we smelled the ethanol directly, the odor was not found.
"Even though the finished product's analytical testing passed all requirements, we had been holding batches pending the outcome of the investigation," continued our agent. "Finally, we noticed that we had changed the boiling beads in the distillation apparatus used to repurify the ethanol after use. Using new boiling beads to distill some alcohol, we used this in a small pilot of the process, and we found the odor. A 10-to-1 dilution of the alcohol with water resulted in a material where we could smell the contaminant. This is now part of our test for redistilled ethanol. The numerous batches made during this time? Rejected."
Pharmaceutical Technology's monthly "Agent-in-Place" column distills true-life cautionary tales from the files of Control, a senior compliance officer. If you have a story to share, please email it to Control at [email protected]