Calibration is essential for guaranteeing process conditions such as temperature, atmospheric pressure, air humidity and ingredient dosing. “If each instrument does not stay within acceptable bounds and if its readout does not provide the correct measurement value, product quality can be compromised,” explains Bjarne Sjödell, project manager at the Stockholm-based consulting firm, Acando.
Like all facets of drug facility operation, calibration is strictly governed by the U.S. Food and Drug Administration’s (FDA) Good Manufacturing Practice (GMP) requirements. At many drug manufacturing facilities, tradition has prevailed, and processes have remained manual and paper-based, often resulting in management challenges. Until fairly recently, this was true at AstraZeneca’s CTS tableting facility in Södertälje, Sweden.
The facility’s management wanted a calibration system that would reduce the redundant processes stemming from 12 separate databases and five different workflows. Users also hoped to be able to reduce the number of calibrations required for robust instruments, and to highlight any adverse performance trends on specific sensors or instruments before they drifted out of tolerance and resulted in production or quality problems.
Three years ago, the facility installed a digital calibration management system that, AstraZeneca reports, has been yielding a number of positive results, streamlining databases and work processes, and even allowing the time intervals between calibrations to be increased, thus reducing equipment downtime. “In the past, calibration was done to a large extent with manual and paper-based processes. The certificate was on paper, which was signed and archived in binders,” explains Sjödell, who walked AstraZeneca through the implementation.
The new process means that the entire flow happens digitally, from measurement to signing and archiving of certificate. “Previously, 41 people at the facility worked on calibrations. Today, the number is 30,” Sjödell adds. Work processes have been similarly streamlined, as has the number of databases required to store calibration data. Acando helped AstraZeneca Sweden develop one single, shared work process for all production facilities, replacing five previous work processes. Meanwhile, data from a dozen separate databases has been consolidated into one shared data repository.
Now the entire framework for calibrations is situated in this repository, including tolerance levels and measurement-point descriptions for all instruments, legitimacy levels, time points for measurements and all protocols, reports and certificates from earlier measurements. Operators make process measurements and access the system via handheld computers and portable multifunction calibrators. Calibration results are automatically stored in the multifunction calibrators or entered manually into the handheld computers.
Thereafter, the results are automatically downloaded from calibrators and handhelds into the main system. If any calibration level is outside the acceptable limits, the affected measurement is rejected, triggering a deviation investigation. Not until the calibrations are electronically signed by the person who carried them out are they considered complete and stored in the database.
Acando developed a new work process for calibration, and AstraZeneca opted for the Beamex CMX calibration technology platform. Since its implementation last year, users say the paperless system has allowed AstraZeneca to change calibration intervals and increase product quality and manufacturing efficiency.
Analysis and Access
“Our calibration process is much more organized now, as is our planning, while workloads are more even,” says Per-Olof Isaksson, manager for Service and Technique at AstraZeneca. “I think the biggest effects will be realized when we start to analyze trends and deviations over time and can find solutions to make the work more effective.”
Compliance with 21 CFR Part 11 was essential for the new solution, and a key reason why the Beamex platform was selected, explains Isaksson. The new solution will provide the most benefit by making statistics and trend data readily accessible, says Isaksson.
Historical trend analyses can be performed more easily and quickly than before, he says, and everyone in the organization can make use of the statistics in a simple way. “Now that we have all the historical measurement data digitally stored in an accessible system, we can easily analyze the calibration trends for respective instruments,” Isaksson notes. “We can thus identify instruments and sensors that remain stable over a long time, which means the calibration interval for these instruments can be extended without any impact on production or quality. For example, the interval could be changed from yearly to once every two years.”
Calibration would be performed more frequently on instruments that are found to give uneven measurement results. Each year, about 21,000 instrument calibrations are performed within Sweden Operations, and Isaksson believes that the digital system could allow this number to be halved.
“We are going to save a lot of time and money by increasing the intervals between calibration,” he says. “We’ll also reduce the downtime that results when machines must be shut down for a calibration.”