Of Audits and Gunk

Published on: 
Pharmaceutical Technology, Pharmaceutical Technology-09-02-2009, Volume 33, Issue 9

Thanks to their keen observations, these auditors reveal the true culprits of deviations.


"You know it's going to be a bad day when someone comes into your office and says, 'It can't be fixed, we know what the problem is, and here's the deviation report,' and then leaves," says our GMP Agent-in-Place. "The deviation was happening during the filling of a liquid injectable product. Stopper popups were occurring between stopper placement and capping. This problem had happened before on this product, and we had checked the obvious suspects, including stopper diameter, vial-opening diameter, vial-opening finish, set-up and operation of the stopper placement equipment, and stopper siliconization. There didn't seem to be anything left to check.

"Concerned over potential financial and product losses, management was on our tails. We repeated our investigations and had several experienced staff watch the filling operation from outside the filling room. These observers noticed that the stoppers that popped up often seemed to follow the stopper placement equipment plunger back up a little before dropping. When they dropped, the vial often had started to move, so the stopper was not in the right place and was tipped (popped). The primary cause for the popups was that the plunger was getting 'gunky' and would stick to the stopper. The immediate solution was to stop the line every hour, clean the plunger with sterile disinfectant, and rinse it with sterile water. The longer-term solution was using a different siliconization process for the stoppers."


(de) Foiled again

"We had a product that needed hospital unit-dose packaging, and we didn't have the equipment," says our GMP Agent-in-Place. "So we did what many manufacturers do and contracted out.

"We had complaints of foil delamination in the hospital unit-dose product.Because it was packaged by the contractor, we sent the complaint to them for investigation. They soon wrote back that their investigation showed no possible cause at their site, and suggested we interview the complainant to see what they had done differently.

"In the meantime, we reviewed the packaging record copy for the batch that we had received from the contract packager. We saw annotations in the record indicating that they had serious problems in the packaging of the batch, problems in the adhesive application, and numerous starts and stops. How could the contractor's quality assurance department not have seen this?

"We immediately organized a for-cause audit. But the product was a low-volume generic, and we had to stop all manufacture."

Not documented, out of work

"During an audit of a laboratory analyst's work, I focused on the laboratory notebooks where all the data for the individual tests were to be recorded," says our GMP Agent-in-Place. "Our firm requires that the data must include all critical test information such as weights of the standard, weight of the sample, dilution factors, equipment settings, and all calculations. I discovered that gross and tare weights and net-weight calculations were recorded in the front pages of an analyst's notebook, without attribution as to the test done, date taken, or the material being tested. The net-weight information was apparently then transferred to the appropriate test page. Because the employee had been warned about documentation before, the analyst's employment was terminated. We referenced an investigation, annotated the laboratory notebook pages, and retrained the other analysts."

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.