Not shaken nor stirred
"We made the product the same way every week," says our GMP Agent-in-Place. "The batch record instructions were clear: 'Turn
on the mixer while adding the solvent. Start the filtration.' But someone forgot about the mixer, and the filtration was started.
So when filtration took eight hours instead of two hours, we knew things weren't normal.
"We completed a deviation document, and the manufacturing manager didn't want to report the real root cause (i.e., 'Idiot
employee forgot to start the mixer even though the batch record instructed him to'). To complicate this, we had to perform
extensive laboratory analysis and characterization of the batch just to have even a slight chance for release."
"My job was to review batch-record changes against new drug applications (NDAs) to ensure we had complied," says our GMP Agent-in-Place.
"If everything was copasetic with the NDA, I signed the records. Seemed simple enough, except the process called for my signature
on every page of the batch record. There were four signature slots on each page. I learned later that the reason for this
unusual process was that the manufacturing staff couldn't be trusted not to change a page in the middle of the record without
Fired for purification's sake
"We contract-manufactured a product, and the product's owners asked for a higher purity material," notes our GMP Agent-in-Place.
"But they didn't want to pay for the development and this was a marginal business for us, so we declined. One of our employees
thought he might be able to develop this product and perhaps start his own manufacturing business. Unfortunately, he began
by loading a costly stainless-steel purification column already filled with media onto his truck. He was easily found out,
and immediately fired, although the company never filed formal charges."
No validation necessary
"It was an older product, predating the original GMPs," our GMP Agent-in-Place reports. "Frankly, we never kept up with the
changes in regulations for this product since we built our factory in the 1950s. Naturally, FDA inspectors thought that we
should be using pharmaceutical-grade equipment and controls, as well as validating the process.
"From our business standpoint, there were two problems with that. First, the potency test method still used an animal model,
and it looked to be a horrible challenge to bring it to HPLC or some modern testing technology. This was partly a result of
the unknown purity of the raw material and the unknown activities of the impurities. The animal potency test was also much
too variable for use as the basis for validation. Second, the product was very small and not a significant profit center.
Spending scarce resources on such an item was not smart business, as far as we were concerned. So we did what was logical:
We announced we would be terminating manufacture.
"The following week we were in Rockville for a meeting with a roomful of FDA staff, including the district director and the
district inspection director. The agency representatives noted that we were the last manufacturer of the product, there was
a critical need for it, and FDA wouldn't allow us to discontinue manufacture. The result was that we could continue to manufacture
the product using our historic process and potency test method, without validation. Even the district director agreed to follow
the agency's lead and not inspect the product to modern standards."
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.