Mysteries and Mishaps

Mar 02, 2006

Disappearing act


Control
"Our anti-acid product had a formulation that included simethicone as an anti-gas ingredient," reports our GMP Agent-in-Place. On one particular occasion, the batch record clearly showed that simethicone had been added and the event was witnessed. "But when the finished product was tested for simethicone, it failed miserably. No simethicone was detected!" When repeated testing confirmed no simethicone present, the employees involved were disciplined and the batch was rejected.

Says our GMP Agent-in-Place, "We never found out what really happened."

A lot to miss

"It was a typical blow–fill–seal machine," reports our GMP Agent-in-Place. The automated machine took plastic resin, heated it, blow-molded the plastic, filled the resulting container, and heat-sealed the plastic container. The lot number and expiration date were debossed into the plastic using metal inserts in the molds containing the required information.

On one particular operation, there were 30 molds used simultaneously. "The operator had trouble removing one lot number. One out of the 30 plates had to be swapped out and the operator didn't do it," reports our GMP Agent-in-Place. "The operator evidently forgot about it, and during line set-up checks the mistake was never caught." In-process checks by manufacturing and quality personnel missed this lot number as well, and the batch was merrily released.

"Then the complaints came in," grumps our GMP Agent, "and it was clear what had happened. The five connected containers contained four matching lot numbers and one different lot number. The different lot number was for the previous lot on the machine."

"The resulting recall was a no brainer," reports our Agent. "Our corrective actions included instituting a system to put a 'blank' set of molded containers in the batch record to show the correct lot numbers on set-up and to be verified on the floor by the manufacturing supervisor and the quality assurance floor inspector. The batch record auditors then could provide a second check on this during batch record review and product release."

WFI: warrant for inspection

"It started out as a routine FDA inspection," reports our GMP Agent-in-Place. "Then the FDA inspector looked into a mechanical space that had a variety of piping installed. With black iron piping connected with threaded fittings to stainless steel piping and a 4-foot dead leg, it was hard to tell what was what."

By the time the inspector got through with his questions, he determined that all this piping was part of the water-for-injection (WFI) system. Then, he wanted to take a picture of the mechanical space. "Our policy was that no one took pictures, which the inspector knew, so we refused," says our Agent.

"We told the FDA inspector that we would acknowledge the description, and that a picture wasn't needed. But he was adamant and left, only to return with a warrant and a Federal Marshall!"

The warrant allowed the inspector to take a picture of the mechanical space. Our site vice-president agreed to allow the picture, and added that the marshall wasn't needed any more.

"Nope," said the Federal Marshall, "I go with the camera until the warrant is served."

"So we all gowned up in cleanroom jumpsuits, even the Federal Marshall and his gun, and went for the picture," reports our GMP Agent. "A year and about $1 million later, we had a new water-for-injection system."

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

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