Organic chemistry redux
"The quality-control (QC) analyst at our facility has responsibility for sampling our US Pharmacopeia purified-water system
on a monthly basis," says our GMP Agent-in-Place. "We have limited staff, so when she was out with the flu, the responsibility
fell to the QC director. Keep in mind that the QC director wrote the standard operating procedure for the use, maintenance,
and sampling of the system, and is responsible for training all those who use the system. The procedure includes the use of
bleach before sampling, followed by a thorough flush to remove contamination. When the sample results were received, the total
organic carbon was 100 times higher than the limit. It was revealed through the out-of-spec investigation that the QC director
used isopropanol to sanitize the system. Apparently he didn't think the change would make any difference."
( PAUL GILLIGAN/GETTY IMAGES)
Now audit the deviation
"We have a big, global enterprise resource planning (ERP) system," says our GMP Agent-in-Place. "The validation plan is very
specific and requires auditing at specific intervals of the project, including at each milestone or gateway. The auditor checked
the paperwork against the entry and exit criteria for each phase.
"During the project, management hired a third party to perform an overall audit to be sure we were on the right track. The
third party found that the internal phase audits hadn't been done. In addition, gateways were passed and new phases were
started without waiting for completion of all criteria noted in the validation plan, thus making the in-process step audit
impossible as written. Now, we not only have to respond to the third-party auditor finding, but we also have several deviations
to create and address as part of the project," said our Agent-in-Place.
Who's providing the oversight?
"Our clinical group asked for help from our GMP audit team," said our GMP Agent-in-Place. "There was something funky going
on with a clinical packager, and they wanted someone with a lot of manufacturing experience to do an investigation. The group
was sure the problem was the contract packager and suggested it be shut down.
It was pretty simple in the end. The contract packager wrote up a specification based on our label text and criteria. But
our label text said to use 'one vial placebo (25 mL)' and their specification said to use 'one vial drug product (25 mL).'
Clearly, the packager made a mistake. However, the packager's specification had been signed by our clinical project manager,
thus indicating that it was acceptable. Oops on both parties," laughed our Agent-in-Place.
"Our product was a time-release capsule," writes our GMP Agent-in-Place. "One of the presentations is in unit-dose blisters.
During a particular packaging run, the trimmer was set up incorrectly, and a critical part of the label text was trimmed:
the first digit of the dose. As a result, the blisters looked like they contained a dose of 50 mg, rather than 150 mg. The
mistake was not discovered until after we received a customer complaint, which ultimately resulted in a product recall. At
least five people were responsible for the trimmer's correct setup, production, product inspection, and finished-product release,
and none had completed his job."
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.