Total Recall

Glassy eyed

"You'd think we would learn," groused our GMP Agent-In-Place. "We've had frequent issues with glass defects in our filled parenteral products, which have included significant Form 483 observations over the years. One batch of a large parenteral product filled into glass vials failed our final visual inspection for cracks. The resulting investigation included an evaluation of the entire glass handling and filling sequence. We found that forklift drivers carrying the incoming glass were not as careful as they could have been in setting down the pallets, and the loading device for sterilizing the dry-heat tunnel was banging the glass into place. These problems were corrected. However, since we've had glass-defect concerns for so long, it was disappointing to see we had missed these. What else might we have missed?"

Blistering problem

"Like many pharmaceutical manufacturers, we purchase medical devices to package with our products to form an administration kit," our GMP Agent-In-Place began. "One such device was a reconstitution spike that is used by the customer to add water to our freeze-dried sterile product. The device was blister-packaged and sterilized. On one occasion, a quality check showed pinholes in the blister, and thus the sterility of the device could not be assured. We identified the source of the problem: the ribbon pins for the dot-matrix printer used to print the lot number on the blister were hitting the blister directly, causing holes. Unfortunately, the product was part of a much bigger lot that was already in distribution. We ended up doing a field correction and sending customers a sterile device, requesting that they reject the devices sent in the package."

I don't recall

"If you watch the recall news carefully, you will see that alcohol swabs have been recalled a couple of times in the past 20 years for nonsterility," noted our GMP Agent-In-Place. "The first time it happened, we knew our company was affected because the problem involved our direct supplier. The second time, we thought we were safe. Unfortunately, we sold a product made by a third party that included the recalled swab. Although FDA didn't request the product be returned, we still had to inform our customers of this issue across 13 countries and 500 affected batches. Ouch."

Lab-house blues

"The intermediate product was blue, but it was supposed to be white," exclaimed our GMP Agent-In-Place. "After questioning the employees, one admitted to losing a ball-point pen in the batch, and the process extracted it with the active material. Our investigation was impressive, especially with regard to the comprehensive testing performed and the detailed safety assessment. Although we could remove the blue color with normal downstream processing, there was no way to assure that all chemical components of the ink would be removed. We processed the intermediate material into a set of vials for use as laboratory in-house controls. The controls were needed in any case. I wasn't happy with the proposed corrective and preventative action, which was a 'Be careful using pens' admonishment for the employees. In the end, we sewed shut the breast pockets of the operators uniforms to reduce the likelihood of a repeat."

Pharmaceutical Technology's monthly "Agent-in-Place" column distills true-life cautionary tales from the files of Control, a senior compliance officer. If you have a story to share, please email it to Control at AgentinPlace@advanstar.com We won't use any names, but if we do use your experience in the column, you'll receive a Pharmaceutical Technology t-shirt.