The challenge
ASTRAZENECA GmbH was founded in 1999 as a result of a merger between Swedish company Astra AB and British company Zeneca PLC. It is one of Germany’s four leading pharmaceutical research companies with sales of Euro755 million and 2200 employees. Production is based at its sites at Wedel, Hamburg and Plankstadt, Heidelberg.
At Plankstadt, the company produces therapeutic drugs in tablet form for the treatment of anaesthesia, infection, pain control, respiratory, cardiovascular, gastrointestinal, oncology and the central nervous system. The site consists of two plants, which work independently of each other. The S5 Dryer plant houses a fluidised-bed dryer, where a variety of tablets are processed. They are then moved to the Cota 48” plant to be coated.
AstraZeneca’s objective was to gain compliance with new FDA 21 CFR Part 11 regulations, required by any company exporting to the American market, whilst meeting G@MP4 standards. This meant replacing the existing process control system’s hardware and software in the Cota 48” and S5 Dryer plants with new technologies.
Requirements included electronic records for production procedures, electronic signatures, an audit trail for production procedures, redundant batch control, batch documentation in compliance with 21 CFR Part 11 (batch record), an audit trail of all operating actions performed during the process, and and audit trail of all arisen events and alarms.
As its process control system could not be easily modified to enable compliance, AstraZeneca contracted Felten, to replace the system’s hardware and software at the two plants.
The project was divided into two stages. Stage One comprised the replacement of the existing control system using CitectSCADA.
Stage Two entailed the Siemens Teleperm M AS-230F system. Here, Felten utilised the high performance Teleperm driver inherent in CitectSCADA to interface with it via a local bus (CS-275).
Subsequently, Felten and Citect partnered to produce CitectSCADA Batch, which is based on the process management system installed at Plankstadt. CitectSCADA Batch handles the operating, monitoring, process control and reporting of process data; the administration of production and order master data; the administration and creation of FDA-compliant batch reports; and the tracing of all process parameters as well as a comprehensive audit trailing.
The requirements
IN choosing a replacement for the process control system’s hardware and software, the following requirements were important:
Electronic record and electronic signature compliant in the fields of electronic records and process controls.
Processing of the project in compliance with the FDA’s validation life cycle.
Operational safety and reliability due to redundancy.
Modern system architecture, which could integrate into the existing plant and extend to enable future enhancements.
Operation and documentation according to FDA 21 CFR Part 11.
Description of the plants and processes
THE Cota 48” and S5 Dryer plants are designed to be explosion-proof and operate under strict safety conditions due to their potentially hazardous materials. Both plants work with a Siemens Teleperm M AS-230F system.
Instead of replacing the Teleperm system with a PLC, Felten utilised the high performance Teleperm driver available with CitectSCADA to interface with it via a local bus (CS-275).
Each plant has an operating and display client, which connects to the redundant CitectSCADA servers via Ethernet.
AstraZeneca’s local network, in turn, connects to the plant via Ethernet. The operating and display components in the hazardous production area have a mouse, touch-pad keyboard, barcode scanner and TFT display.
An existing AstraZeneca file server is responsible for swapping out data for long-term archiving. The process system uses the real-time information available from CitectSCADA and the batch system to create FDA-compliant, unalterable batch reports.
S5 Dryer plant process
AT the S5 Dryer plant, a fluidised bed dryer is used for both drying and building up agglomerates, through the use of an integrated spraying system.
The process involves a fluid being sprayed onto the fluidised bed, which then forms into granulates. Next, the granulates go through a drying phase, which fixes and transforms them into agglomerates.
The whole process is fully automated in accordance with the process flow. The agglomerates are subsequently pressed into tablet form in a separate production unit.
Cota 48” plant process
THIS automated process flow coats the tablets with a defined quantity of active agent whilst complying with FDA production regulations. The process is controlled and monitored automatically, as follows, using a batch control system:
Production of a sprayable active agent.
Process planning phase.
Selection of the order to be produced.
Start of the automated batch run (production in accordance with FDA compliant production procedures).
Spraying phase.
Spraying of the active agent in accordance with production specifications.
Cooling and following evacuation phase (manually).
Printing of the batch report, which requires FDA-compliant archiving and documentation.
Compliance with customer’s objectives
THE customer’s objectives were defined in a URS and worked out using comprehensive engineering specifications (FDS/HDS/SDS/MDS).
Through the implementation of the integrated CitectSCADA and batch solution, Felten met all AstraZeneca’s requirements with regard to facilitating FDA-compliant production and documentation, fulfilling the demand for exporting to the American market.
These included FDA-compliant production, software and hardware that can be validated, and an ER- and ES-compliant process control system, which integrates with the existing Teleperm AS-230F.
The integrated solution provides a system that manages operating, monitoring and process control; reports process, production and order master data; and ensures production planning. FDA-compliant batch reports are easily created, and the tracing of all process parameters and comprehensive audit trailing are ensured.
Felten’s project management was the foundation for the successful realisation of the FDA-compliant project. The project was managed to G@MP standards.
System performance: The system was designed so that, during commissioning, it could be switched to the new system during production-free phases. As production was not interrupted, commissioning and fine-tuning incurred no downtime.
Special project functions: The system has a highly developed rights and user administration. It is possible to allocate runtime-defined functions to a user group. All the system’s user operations are carried out in compliance with ER and ES, and therefore meet the requirements of FDA 21 CFR Part 11.
Reducing engineering expenses: The development of genies for the Teleperm system as well as a comprehensive data management, which enable audit trailing and consequently the ER- and ES-compliance, has reduced engineering expenses.
Conclusion
THE new system allows AstraZeneca to increase productivity and maintain the high quality of the drugs it produces at its Plankstadt site. Scalability means AstraZeneca is able to upgrade easily and at minimal cost to meet future requirements.