Monitoring system for the new construction of the pharmacy of the Saarland University Hospital

For the new construction of the pharmacy at the University Hospital of Saarland, a cleanroom monitoring system was required in the GMP manufacturing area as well as for the unit-dose area to monitor environmental and process parameters. Additionally, temperature mapping was needed for several storage areas, which were subsequently connected to the monitoring system. The pharmacy, as a central service unit, ensures high-quality and cost-effective supply of medicines to patients in the hospital. In recent years, the central preparation of patient-specific medicines, especially ready-to-use cytostatic solutions and patient-specific blistering of solid oral medicines, has become increasingly important.

For the implementation of the project, the university hospital chose the comprehensive BRIEM monitoring system. The requirement for the cleanroom monitoring system in this project was to record, monitor, and archive quality-relevant measurement data and alerts in GMP sterile manufacturing, production, blistering, and storage, as well as external alarm notification. The monitoring system had to handle threshold alarms and measurement data recording (trend functions) in accordance with the requirements of 21 CFR Part 11 and fulfill the necessary alarm tasks via suitable interfaces. It was particularly important to the customer that a building overview could be displayed, providing an overview of the monitoring status in individual rooms, with the ability to switch to detailed views of the monitored measurement points. In the detailed view, the operator should be able to observe individual measurement points, detect threshold violations, and acknowledge them. For GMP reasons, the system must be equipped with access protection. Regarding alarm notifications, the customer emphasized that a distinction should be made between alarms and warnings. The user should be able to decide for each measurement point whether to report a threshold violation or not. Additionally, the software needed modules such as Audit Trail, Alarm Log, Layout Plan, User Management, Visualization including diagram generation, Trends, and Batch Report Generator.

With the holistic monitoring system from BRIEM, all operator requirements can be met. In the manufacturing area, the system monitors room conditions such as pressure, temperature, humidity, particle concentrations, and airflow velocities in safety cabinets, as well as particle concentration in Class B rooms across 15 rooms or pass-throughs. Refrigerators and deep-freezers in the manufacturing area were also connected to the monitoring system. For environmental monitoring in the unit-dose area, existing sensors were connected to the system. To demonstrate the suitability of storage rooms on different levels according to the EU-GDP guidelines, temperature mapping was first carried out in the rooms to identify the hot and cold spots.

On-site Implementation

To measure environmental parameters such as differential pressure, room temperature, and humidity in the cleanrooms for cytostatic production (GMP-B), sterilization (GMP-B), and preparation (GMP-D), BRIEM combo panels were used. The cleanroom panels, with fully integrated measurement technology and a graphic display for visualizing room parameters, were flush-mounted into the cleanroom walls. Outside the GMP areas, BRIEM surface-mounted measuring devices were installed to record room parameters (pressure, temperature, humidity). Both devices allow for comfortable calibration of the sensors in their installed state.

Particle measurement in the GMP areas was performed using particle counters with external pumps. The pumps were placed in the technical area, providing very easy access for maintenance. All measurement points used hose lengths according to the specifications of Annex 1 of the EU GMP guidelines, kept as short as possible (<= 1 meter). The particle counters of the safety cabinets are automatically activated as soon as the respective workbench is turned on. For alarm notification, three-color LED warning lights and horns were installed in the preparation and in the two manufacturing rooms. Additionally, an 18.5" touch-panel PC was installed in the preparation area. This provides an overview of the room parameters in the various rooms via monitoring software and allows access to detailed views. For temperature monitoring in the storage area, Ethernet and wireless sensors were connected to the monitoring system.

The central core, as with all BRIEM monitoring systems, is the control cabinet combined with the self-developed monitoring software. All sensor measurement data and control and alarm elements are collected here and can be managed via this interface. Before delivery, the control cabinets were fully tested at the factory in Nürtingen by BRIEM together with the customer as part of the FAT test. The entire system was qualified by BRIEM qualification engineers according to GMP, and all sensors were calibrated on-site.

The Result

The pharmacy of the University Hospital of Saarland features a state-of-the-art, comprehensive cleanroom monitoring system in its GMP manufacturing and blistering area for high-quality medicines, as well as in the subsequently connected storage area. In addition to monitoring all relevant environmental and process parameters, refrigerators, freezers, ultra-low freezers, and cold rooms are efficiently integrated into the monitoring system. Besides extensive support for documentation for authorities, the holistic system ensures that the operator is always informed about the status of all critical parameters during manufacturing, blistering, and storage, and can intervene at any time if necessary. In the event of threshold violations, the system reliably notifies via the installed alarm concept, allowing for immediate response.