The Cold Shoulder

Published on: 
Pharmaceutical Technology, Pharmaceutical Technology-07-02-2010, Volume 34, Issue 7

Reports of overlooked controls, dropped pallets, and misplaced documents leave a chill in the air.

Too cool

"The slurry temperature specification for an in-process step was 0–5 °C," began our GMP Agent-In-Place. "When we reviewed the chart recorder temperatures for release to start the next process, we discovered that the slurry had gone below 0 °C, down to -0.6 °C. It was only through a detailed review that we realized that the batch record was the root cause. The record said to cool the slurry to between 0–5 °C, but did not give a set point for the temperature controller.

"The operator, wanting to hurry the process along for us (probably based on long experience with his supervisor asking him to hustle) set the temperature controller to below 0, which resulted in the deviation. In the end, we still released the material because the temperature was set primarly to protect the product from unwanted degradation, and colder is better. Oh yeah, we also added a set point to the master batch record," our Agent noted.

Off the hook


"We have a process in our plant that involves handling pallets in a sling, similar to what you would see under a helicopter," explained our GMP Agent-In-Place. "A safety clasp on the hook failed when one pallet was 6 inches from the floor. Even though most of the glass bottles were intact, we elected to destroy all materials on the pallet because it would have been nearly impossible to inspect all the minute cracks in potentially damaged bottles of product. We modified all the safety hooks in the plant to be sure this wouldn't happen again."

Platoon, about face!

"We have a complicated potency test for one of our products," our GMP Agent-In-Place began. "Because it is a long, involved test with expensive reference standards, we like to perform multiple samples at once, which we refer to as 'platooning.' In one instance, our platoon included two lots that needed to be tested for release and stability. They both failed to meet specifications!

"Although an initial review of laboratory and batch records didn't reveal a smoking gun, exploratory testing on other lots showed there was a laboratory error," our Agent continued. "Based on the Judge Wolin ruling (US vs. Barr Labs, Feb. 1993), we performed a seven-fold retest for each failing sample and ultimately demonstrated that the original results were invalid. The laboratory records didn't show any discrepancies, but we determined that the preparation of the reference standard was the root cause of the failure and took action with the responsible laboratory analyst."

Short on substance

"We hired a consultant to help analyze our electronic-document control system needs and to recommend a system," grumbled our GMP Agent-In-Place.

"Instead, we received an alphabetical list of all available software providers with no pros, cons, or prioritization suggestions. We provided oversight and redirection to the consultant to give him a second chance to meet our desired outcomes. We're now examining our contract to determine whether we have any recourse."

Paperless office

"We recently received a call from FDA," our GMP Agent-In-Place began. "They had logged our sample and the release protocol into their system, but had lost the paperwork, and were calling to obtain a replacement copy. We express-mailed the replacement so we could receive the necessary lot release. Now that's a paperless office!"

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.