"We used a single-use specialized nanofilter for decades," began our GMP Agent-In-Place. "We were an innovator in our particular use, and during the FDA-approval process we had to develop a unique integrity test for the filter. Our supplier noted the filter was difficult to make and experienced many rejects. Some filters failed during integrity testing. We were the last customer they had for this specific nanofilter as they had convinced their other customer to change over to a new filter. The suggested replacement for our older filter was $700. The filter was a new technology filter priced at $5000—still single-use. However, we did not make the replacement filter pass qualification testing in our process. Because the supplier was insistent on canceling production, we looked at other suppliers. We finally found a filter that would fit in our process (at $3000 each). However, the integrity test required use of suspended and standardized gold particles which added several thousand dollars to each use. People wonder why pharmaceuticals cost so much, well, our costs went up a half-million dollars a year because the supplier discontinued its product."
Caustic quality"When your bioburden trend goes out of control, you need to take action," our GMP Agent-In-Place noted. "We had a nonsterile process in which the bioburden was increasing, and the manufacturing staff was not finding the source. The Quality team spent time on the manufacturing floor during all shifts to watch the activities. While we were there, the bioburden went back to historic levels, although no new activities had been instituted. It was only when the investigation team started reviewing equipment log books that they realize that during the bioburden excursions, the standard operating procedure that required caustic soak of the vessels had been forgotten."
"We had just switched from distributing our product directly from the manufacturing site to using a third-party logistics (3PL) partner," said our stunned GMP Agent-In-Place. "Our release computer system was linked to the 3PL's computer system, which used a two-step release process. Step one involved the manufacturing site release information and step two focused on the transit temperature review. When these requirements were met, the computer system would automatically release the batch. After our usual validation testing and approval, we turned the process on. Unfortunately, there was a bug in the configuration of the live system and some batches were released without the proper prerequisites. Luckily, we were carefully watching the system during the first couple of days from two different sites and caught the issue before unreleased product was distributed. We quickly tweaked the configuration and now the system works as desired. Lesson learned: the test system isn't always completely identical as the live system."
"We had two manufacturing sites located in the same city," said our GMP Agent-In-Place as he began his complaint. "The sites shared the Quality department. Also, the supplier-qualification process included testing and auditing. Both sites performed extensive remodeling, which required several automated cleaning processes, and each site had new procedures for cleaning and disinfection. The projects were run by separate groups, so each picked its own new clean-in-place agents and disinfectants. Each group needed extensive laboratory characterization and test development as well as numerous supplier audits. And each team insisted that its different equipment vendors 'required' these new and unique materials. Yes, we did get all the necessary laboratory work completed and did successfully perform the audits. But a little coordination up front would have saved several hundred-thousand dollars.
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 [email protected]