There are an ever-increasing number of strict rules and regulations for Good Manufacturing Practice (GMP) and Good Automated Manufacturing Practice (GAMP) compliant products, and compliance with these rules and regulations needs to be observed as a part of a company’s quality management system.
For this purpose a customised cleanroom monitoring system is a very helpful instrument. Ideally, the monitoring system will document the critical environmental and production parameters automatically, continuously and completely – without further effort. The system allows the user to intervene if parameters differ from the desired value and records the actual parameters so that they are verifiable in the long term.
| A cleanroom monitoring system should provide: |
| Holistic project management from planning to maintenance |
| Investment safety due to modular system structure with possible extensions and amendments (e.g. adding refrigerators) |
| Multistate alarm and warning concept with several escalation levels |
| Audit safety due to complete GMP documentation |
| Short training period due to an intuitive operating concept for devices and software |
| Optimised life cycle costing (LCC) consideration, including acquisition cost, availability, maintenance, support and possible extensions |
To make the monitoring system a useful tool, the facility’s life cycle must be taken into consideration right from the planning stage. This is the only way to make sure that the system does not unnecessarily impede production procedures and supports the users in their day-to-day work, sparing them the extra effort of complex documentation duties.
The basic structure of the holistic cleanroom monitoring system consists of the following modular components: probes to acquire different parameters, visual indication in the cleanrooms (digital displays, touch panels, signal lights), alarm forwarding (telephone, email, text message), data retention and analysis for long-term documentation, user-friendly software allowing for easy intervention, analysis and documentation.
The planning should not start from a technical point of view, because most technical requirements are easily feasible. Much more important is that the system fulfills any product- and user-specific requirements and conforms to the respective rules and regulations.
Therefore the following questions must be answered as part of the planning process:
- Which rules and regulations have to be observed? – Consider the product-specific requirements and approval procedures as well as any statutory requirements regarding the monitoring system.
- Which tasks and possible problems might come up in the future? – Consider, for example, requirements for system extensions, maintenance, adjustable equipment and qualified status.
- In which areas does it make sense just to monitor specific parameters and in which areas should a holistic monitoring system monitor and record all relevant parameters continuously?
- How does the system have to be configured to optimally support the user?
User requirements
Statutory provisions are an important factor from planning to production. In some sectors, e.g. pharmaceuticals, the requirements of GMP, GAMP and the FDA must be met to acquire the necessary manufacturing permit. The demands of the monitoring system should directly relate to this.
The first step is to draw up the user requirements specification (URS). Three factors should be considered to define the basic requirements:
1. Production process for the respective product (cleanroom class, safety aspects, storage).
2. Risk factors concerning the product (sensitivity to temperature or humidity changes).
3. Requirements regarding the monitoring system.
Customer-specific wishes and demands should also be taken into account, for example:
- Hygienic design – flush mounting, stainless steel measuring instruments.
- Quality of measuring equipment – What is the permissible allowance for sensors? Are refrigerators or climate cabinets involved for which high-precision measuring instruments are required due to the very low permissible tolerance?
- Design – Where should the displays and alarm indicators be located in the cleanroom to inform the personnel effectively during the production process?
It is important that employees who will be working with the system on a daily basis are included in the planning. After defining the requirements the system supplier will issue the functional specification document (FSD) to specify how the user requirements will be put into practice. The user should review the FSD and adjust it if necessary. Then production in the supplier’s facility can begin.
The Factory Acceptance Test (FAT) should also take place there. For the FAT, the complete system has to be assembled and tested to allow the customer to assure themselves of the system’s functionality and quality before the components are installed in their own facility. After the successful FAT, the next step is the installation of the components at the customer’s facility and after that, the commissioning of the system including the installation qualification (IQ), operational qualification (OQ) and GMP compliant documentation on site.
User training
An important point is the user training, which should take place after the commissioning when the system is fully functional to ensure that the users learn to work with their customised version of the system.
Displays and alarm indicators should be located effectively to inform personnel while carrying out their daily operations
As soon as the commissioning and qualification is complete, the system can be used in the production process. However, the system’s ‘life cycle’ – according to GMP – continues. The monitoring system has to be maintained and the sensors must be re-calibrated at regular, predetermined intervals, usually every 12 months. Therefore it is important to ensure from the beginning that the system can be readily maintained once built in. The sensors, particularly, have to be calibrated along the complete measuring chain and adjusted if necessary. The maintenance must be completed according to the maintenance plan and the process has to be documented accordingly.
Should the necessity for system extensions or amendments arise during operation, these changes must be implemented in compliance with predetermined standards (change control) and must be documented accordingly. This may become necessary if the monitoring system has to be extended when adding incubators or climate cabinets or measuring instruments with different limit values. In such cases, these amendments have to be planned, implemented and documented in compliance with GMP guidelines to ensure the continued qualified status of the system.
