AstraZeneca. CaseStudy. Batch solution facilitates compliance with FDA regulations at AstraZeneca s Plankstadt site THE CHALLENGE

Transcription

1 AstraZeneca Batch solution facilitates compliance with FDA regulations at AstraZeneca s Plankstadt site THE CHALLENGE To comply with new FDA 21 CFR Part 11 regulations whilst meeting the G@MP4 standards. THE SOLUTION AstraZeneca contracted FELTEN to replace the existing process control system s hardware and software with a fully integrated CitectSCADA system. CONCLUSION The integrated process control system allows AstraZeneca to comply with FDA 21 CFR Part 11 regulations, meeting the G@MP standards and the demands of the American market. The reliability of the new system allows them to increase productivity and maintain the high quality of the drugs it produces whilst its scalability means the company can upgrade easily at minimal cost to meet future requirements. THE CHALLENGE AstraZeneca GmbH was founded in 1999 as a result of a merger between the Swedish company, Astra AB and the British company, Zeneca PLC. It is one of Germany s four leading pharmaceutical research companies with sales of 755 million 1 and 2,200 employees. Production is based at its sites at Wedel, Hamburg and Plankstadt, Heidelberg. At its Plankstadt site, 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 fluidized-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 come into compliance with new FDA 21 CFR Part 11 regulations, required by any company exporting to the American market, whilst meeting the G@MP4 standards. This would mean replacing the existing process control system s hardware and software in the Cota 48 and S5 Dryer plants, with new technologies to facilitate FDA-compliance. Requirements included: Electronic records for production procedures Electronic signatures Audit trail for production procedures Redundant batch control Batch documentation in compliance with 21 CFR Part 11 (batch record) Audit trail of all operating actions performed during the process Audit trail of all arisen events and alarms CaseStudy

2 FELTEN required a modern extensible system As its existing process control system could not be easily modified to enable compliance, the company 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 replacing the Siemens Teleperm M AS-230F system with a PLC. Subsequently, FELTEN and Citect have partnered to produce CitectSCADA Batch, which is based on the system installed at the AstraZeneca Plankstadt site. THE REQUIREMENTS In choosing a replacement for the existing 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 the FDA s regulations 21 CFR Part 11 FELTEN implemented CitectSCADA because of its unrivalled reputation for reliability, flexibility and scalability. DESCRIPTION OF THE PLANTS AND PROCESSES The Cota48 and S5-Dryer plants are designed to be explosion-proof and operate under strict safety conditions due to the potentially hazardous materials. Both plants work with a Siemens Teleperm M AS-230F system. Instead of replacing the Teleperm system with a PLC, FELTEN utilized the high performance Teleperm driver available with CitectSCADA to interface with it via a local bus (CS-275).

3 which could integrate into the existing plant 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 the 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 and the process system uses the real-time information available from CitectSCADA and the batch system to create FDA-compliant, unalterable batch reports. S5 Dryer Plants Process At the S5 Dryer plant, a fluidized-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 fluidized 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. PLANT AND PROCESS The S5 Dryer plant produces agglomerates using a fully automated process, which are then pressed into tablet form in a separate production unit Tablets are then coated during the Cota 48 plant process

4 PROJECT RUNTIME Cota 48 Plant Process The aim of this automated process flow is to coat the tablets with a defined quantity of active agent whilst complying with the 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 FDAcompliant production procedures) Spraying phase Spraying of the active agent in accordance with the production specifications Cooling and following evacuation phase (manually) Printing of the batch report, that requires FDA-compliant archiving and documentation (batch record) COMPLIANCE WITH CUSTOMER S OBJECTIVES The customer s objectives were defined in an 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 demands for exporting to the American market which includes: FDA-compliant production; Software and hardware that can be validated; an ERand ES-compliant process control system which integrates with the existing Teleperm AS-230F. Within the 12 month project runtime, during engineering FELTEN ran through all of the Validation Life Cycle phases for the Cota48 and S5 Dryer plants. Validation Plan QM and Project Plan URS FDS Risk Analysis HDS SDS Thread & Control Analysis MDS Code Review Module Test The Validation Plan describes the life cycle as well as the responsibilities and procedures. Planning of validation and qualification activities. The User Requirement Specification describes the demands the system should fulfil. The Functional Design Specification describes the realization of the functionality required in the URS. A function list results from the FDS, from which the Risk Analysis was carried out in partnership with AstraZeneca. The Hardware Design Specification defines the hardware the system runs on, and the connections to existing systems / plants. The Software Design Specification describes the software components as well as the interaction of the subsystems in the complete system. It is the basis of the code creation. Subsequent to the SDS, a thread and control analysis was carried out in partnership with AstraZeneca. The Module Design Specification describes the functions of a software component and its interfaces. During engineering, FELTEN has performed a Code Review (Complying with programming regulations and good engineering standards). The module test proves that the module has been realized as was specified, and that it is functioning. The integrated solution provides a userfriendly process control system, to manage the operating, monitoring and process control; the reporting of process, production and order master data; and to ensure production planning. With the system, FDAcompliant batch reports are easily created, and the tracing of all process parameters and comprehensive audit trailing is ensured. OQ / FAT IQ OQ / SAT PQ The Factory Acceptance Test proves that all software modules / components interact correctly with each other. The Installation Qualification ensures that the hardware to be supplied corresponds to the HDS, and that the hardware has been duly installed. The Site Acceptance Test proves that the system is running in the target hardware according to the specification. The Performance Qualification proves that all functions of the URS have been realized successfully on the productive system.

5 RECORD CONTROL Batch solution facilitates compliance with FDA regulations Table 1 Detailed list of Customer Requirements regarding the control of electronic records and the system Electronic Records Controls Electronic records must be reproducible in electronic and hand-written form. Electronic records must be available for the last 10 years. The system must have the option to have restricted access authorization through the use of electronic signatures. An audit trail must be implemented. This automatic recording must include all actions that create, change or delete electronic records or data. The audit trail must include at minimal, the following information: User ID of the person carrying out actions at the electronic record Local date and time Type of transaction Modification (old value, new value) The audit trail must not be modifiable The audit trail recording, as with the electronic record, must be made available in electronic and hand-written form; available on request within 4 hours. The audit trail recording must be available for the last 10 years. The audit trail functionality must run steadily during the operation of the plant. Users must not be able to modify time and date settings needed for the audit trail. Modifications on electronic records must not overwrite data recorded before. System Controls Passwords should expire/become void after 90 days. Users must not be able to reuse their passwords. The system must provide several authorization groups, which implicate a different functional scope. Starting with login, the system must perform authority checks, based on the defined safety hierarchy. This ensures that a user can only access functions, which are assigned to them. A system administrator must not be allowed to change electronic records, unless this change can be clearly allocated to an individual (User ID). The system must provide read-only access for FDA inspections. The system must be able to detect invalid or modified data independently and to notify/display them. Login attempts, which have been failed, are recorded in the system log and result in blocking the user. FELTEN s project management was the foundation for the successful realization of the FDA-compliant project. The project was managed to G@MP standards by FELTEN engineers, System integrators and Citect Professional Services, highly experienced in the field of visualization and automation. System Performance The system has been designed in such a manner that, during the commissioning period, it could be switched to the new system during production-free phases. As a result, the commissioning and fine-tuning was very production-friendly and incurred no downtime as the production was not interrupted. 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 FELTEN met AstraZeneca s requirements by using CitectSCADA to replace the existing process control system and combining it with a batch solution. This facilitates compliance with FDA 21 CFR Part 11 regulations in order to guarantee the demands of the American market. Instead of replacing the Teleperm system with a PLC, FELTEN utilized the high performance Teleperm driver inherent in CitectSCADA to interface with it via a local bus (CS-275). The reliability of the new system allows AstraZeneca to increase productivity and maintain the high quality of the drugs it produces at its Plankstadt site, whilst the scalability means AstraZeneca is able to upgrade easily and at minimal cost to meet future requirements.

6 With the integrated CitectSCADA and batch solution installed in its Plankstadt site, AstraZeneca is able to produce high quality drugs for benefit of people s health worldwide. Subsequently, FELTEN and Citect have partnered to produce CitectSCADA Batch, which is based on the process management system installed at AstraZeneca s Plankstadt site and includes: operating, monitoring, process control and reporting of process data administration of production and order master data administration and creation of FDAcompliant batch reports tracing of all process parameters as well as a comprehensive audit trailing A batch control system controls and monitors all phases of the Cota 48 plant process, in compliance with FDA production regulations WRITTEN BY Jeannette Ewen, Senior Consultant, FELTEN GmbH FURTHER INFORMATION Contact person on customer s site Mr Huckele, Project Manager, AstraZeneca GmbH Mr Egger, Validation Expert, AstraZeneca GmbH In den Doerrwiesen 31, D Serrig Tel +49 (65 81) Fax +49 (65 81) nikolaus.kranz@feltengmbh.de ENDNOTES 1. Figures from 2001 For further information visit or contact your nearest Citect representative AMERICAS HQ AUSTRALIA / ASIA HQ EUROPE HQ CHINA GERMANY SOUTH AFRICA UK Copyright 2003 Citect Corporation. All rights reserved. Citect and Plant2Business are registered trademarks of Citect Corporation. All other brands or names are property of their respective holders. PR10231