Our GMP Agent-in-Place was briefed by the quality assurance manager who had picked the inspector up at the nearest international airport. "The plant had just undergone its first preapproval inspection (PAI) by FDA the previous week after more than 14 years of successful operation. With the exception of the water-for-injection (WFI) system, the inspection had gone extremely well.
"With respect to the WFI system, it could not have gone worse. During the system walkthrough, the inspector found two nonsanitary fittings on the headspace of the WFI holding tank. When pressed for results of chemical and microbial testing, the site could only provide useable summaries for the last few months. The FDA inspection team told the site management that unless something substantial was done about the WFI system deficiencies, the site would fail the PAI. In near desperation, the site committed to a complete renovation of the entire WFI system to pass the PAI."The inspector plunged into the details of the WFI system. When our inspector asked to see the qualification package for the system, it was slow to arrive and somewhat rudimentary given its age. There were no 'as built' drawings of the system as they existed today, only the originals from the installation. The inspector's first request was for an extended summary of the system's performance. While waiting for the data to arrive, the inspector set off to review the system accompanied by the QA and engineering managers. Sure enough, the nonsanitary fittings were clearly visible, albeit in nonwetted locations on the vent system. The rest of the system looked to be in good order. Comparing the current system to the bold drawings revealed only minor changes, which were well-documented in supplementary drawings.
"The inspector continued with the rest of his visit reviewing other systems, processes and validation studies. All was in reasonable order, with the usual minor observations typical in any overseas audit. The amount of supportive information available was extensive. On the fourth day of the inspector's visit, the long-awaited historical data on the water system were delivered. Throughout the 14 years of testing, the firm had experienced no more than two WFI samples with counts in any year, despite taking an average of more than 4000 samples each year! Endotoxin was never a concern, remaining below the required limits in more than 50,000 samples. The chemistry data were just as impressive, there had never been a sample out of limits.
"The inspector suggested the site revisit the decision to renovate the water system. Corporate compliance refused for fear of endangering the PAI. After all, FDA approved the PAI on the condition of the renovation, if the renovation wasn't going to happen, would the PAI remain approved?
"On a return visit to the site, the inspector toured the newly renovated WFI system. At a cost of several million dollars in capital, weeks of lost production and a large validation exercise, WFI could be made once again without the risk of contamination from two nonsanitary fittings."
A taxing leak
"We were doing some remodeling to the world headquarters of our $2,000,000-in-sales biopharmaceutical company," explains our GMP Agent-in-Place.
"The fire alarm went off, and we all dutifully trooped outside. It soon became apparent that one of the construction workers had set off the sprinkler system, as water was now leaking down the outside of the building. And the room on the inside where the water was leaking from ... was the place we stored the tax files. I think we managed to salvage most of them."
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