Suspicious Times

Agents report unusual chemistry, abnormal data analysis, and unconventional work practices.
Aug 02, 2008

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
. 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.

Denature of de beast


PAUL GILLIGAN/GETTY IMAGES
"We didn't develop the product, industrialize the product, or even choose the contract manufacturing company, but now we own the product, having purchased it from another company," says our GMP Agent-In-Place. "They were probably glad to get rid of it!

"It was a biological product with buffer additions and filtrations; it was actually pretty complicated. The contract manufacturer had been in this sort of business for more than 20 years, so it should have known what its scientists were doing. But they added a pH adjustment buffer too fast, which massively changed the pH value at the local addition point, and the nearby protein was denatured. The denatured protein then clogged the subsequent filtration, and the product that did get through the filter had an odd color. We ended up destroying the batch that would have had a sales value well over $1 million."

It works if you assume it's perfect

"It was an animal-based potency test from several generations ago, and it had a lot of variability," explains our GMP Agent-In-Place. "The test was used both for the bulk raw material and for the in-process potency tests. The in-process potency test was a crap-shoot as to whether it would pass or not. It was my laboratory doing the testing and there was nothing I could do easily about the test because it was an NDA test method.

"I did take a retroactive look at the historical data. It turns out that if you assumed that the bulk raw material is perfectly pure and assign it that potency, you would have had a much closer agreement with the actual test results, and none of the lots would need to be rejected! Things were looking up as we now had a way forward."

Just fill out the form, no one cares

"In our small Midwest facility, it seemed to be business as usual," recalls our GMP Agent-In-Place. "But then an accounting fraud was discovered, and we sent out quality assurance auditors to check if there were any GMP issues as well.

"It turns out that the accounting fraud was only a part of the problem! For instance, people signed for work completed, as if they had done it, but their time card showed they were absent on that day. One person signed that they had cleaned the storage area for 31 consecutive days. We couldn't trust any of the signatures, or if they had done the work, and therefore if the material they shipped met the requirements. In the end we reached an agreement with FDA to recall all the material, and we closed the facility permanently."

Wanna bet?

"The boxes containing product complaints would come to my boss's office," says our GMP Agent-In-Place. "If we had a minute, we would shake the box gently to try to figure out what the product within was. After a while, we were betting on our respective guesses. The price was just a nickel and the rewards were the pool of nickels and bragging rights until the next sample arrived.

"Because our production was mostly one product line, we started needing to guess not only the product name, but also the strength, the exact complaint, and sometimes, the container size. An example of this would be product name, 20-mg tablets, mottled tablets, and 100-tablet bottle size. We got so much into the habit of betting on the boxes that if the a person wasn't present, we'd tape a nickel on the box along with our guess. We kept it up until I changed jobs."