A dud for DOD
"Our stability department was on the ball," notes our GMP Agent-In-Place. "They had reported the pH rise in the sterile ampul
product on the correct deviation form and brought it to the attention of the head of quality. During the 36-month shelf life,
the pH would rise, presumably as a result of extraction from the glass container, because the solution was unbuffered. On
some lots, the pH would rise to values that were above product specifications, hence the deviation.
"Because the pH was not deemed critical, and there was no safety, potency, identity, quality, or strength issue, the head
of quality decided that no actions were needed and the stability deviation was closed.
"However, this was not the end of the matter! The Department of Defense arrived to conduct an inspection to determine whether
a contract could be let to the company for many products, including this injectable. The contract was worth tens of millions
of dollars. The contract was not let, because the injectable product was not meeting specification for pH, and the company
management was very unhappy with the head of quality that allowed this to happen.
"The immediate corrective action was to shorten the expiration dating period, and the development group was given an assignment
to determine what else could be done to support the desired longer shelf life, but no recall was initiated.
"I think this is one of the reasons why the head of quality's employment was terminated."
Ampul cause for mix-ups
"Customers were reporting that our ampul product was getting mixed up with another ampul product that was not the same chemical
entity or even had the same indications," notes our GMP Agent-In-Place. "The mix-ups were occurring because the color of print
and number of printed bands shown were the same, and the product names were somewhat similar. We went to some effort to change
the print color and the number of bands to prevent this from recurring.
"We were really surprised to find that, six months later, the other product changed to our new color and with the same number
of bands, and the problem continued."
The bias problem
"One of our employees was very ambitious and was given a project to 'fix' the stability system at the site," laughs our GMP
Agent-In-Place. "Because the products were relatively inexpensive, he tried to optimize the cost of the stability system by
maximizing platoon testing of the stability samples. He did this by having sufficient retain samples stored to conduct stability
testing as well as for retain purposes. Then, once a year, batches were systematically selected to represent all the storage
times throughout the product shelf life. Samples of these would be sent simultaneously to the lab for analysis."
"Of course the laboratory loved this method. They had only one set up and test per year and could be very efficient. However,
our ambitious employee forgot about the bias of the once-a-year stability test such as the fact that there was a common reference
standard workup, common machine set-up, and so forth that could be considerable. These biases would normally average out in
typical stability programs, but not in this case.
"Our 'ambitious and efficient employee' moved on to other projects at other sites, leaving the bias problem behind for the
'optimized' laboratory to solve!"
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.