The control and monitoring of both storage and production environments is becoming increasingly important for the pharmaceutical industry.
Regulators such as the US Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA) are demanding more accurate measurement and storage of room parameters. If the storage medium is electronic, which is increasingly becoming the case within the pharmaceutical industry, the methods used must comply with 21CFRPart11. This is the FDA regulation that governs the use of electronic records and electronic signatures. However, in 21CFRPart203.32, the FDA also demands that manufacturers, distributors and their representatives must store and handle all drug samples under conditions that maintain their stability, integrity and effectiveness. In addition, such samples have to be kept free of ‘contamination, deterioration and adulteration’.
In order to achieve these conditions, the FDA in regulation 21CFRPart 820.70 lays down what it expects from production and process controls in such areas: “Where environmental conditions could reasonably be expected to have an adverse effect on product quality, the manufacturer shall establish and maintain procedures to adequately control these environmental conditions. Environmental control system(s) shall be periodically inspected to verify that the system, including necessary equipment, is adequate and functioning properly. These activities shall be documented and reviewed.”
Just to make the situation even more complex, there are numerous other FDA rules related to environmental control and monitoring. For example, Part211.42 covers design and construction, Part211.46 ventilation and air filtration, and Part211.142 warehousing features.
As a result, the pharmaceutical industry has been forced to install two types of control system – a building management system (BMS) and an environmental monitoring system (EMS). In some cases this had led to problems with compatibility and even validation.
Help is now at hand, however, with the launch of the BMS/EMS package from Eurotherm, a division of Invensys. A flexible, high-powered solution, it combines the company's expertise with accurate control functionality in the environmental recorder market with its visualisation and central storage solutions from the buildings management market.
The BMS part of the package combines the control of heating, ventilation and air conditioning systems, and EMS solutions. It is used to control, monitor, record and alarm a variety of processes of varying risk to the attributes of the manufactured product. For its part, the EMS is an enhancement of the actual BMS. It uses wrap and comply EMS solutions to monitor and store the critical and non-critical parameters coming from plant technologies (Fig.1). Together, the BMS/EMS solution offers a four-fold advantage to users:
- Easy compliance – including standard validation templates, standard modules, standard review and reporting facilities.
- High availability – redundancy of monitoring, storage and control.
- Scalability – single room to plant-wide package, using phased solutions.
- Easier maintenance – includes calibration and maintenance management, multiple alarming solutions and remote visualisation.
In terms of compliance, BMS/EMS meets all the regulatory requirements mentioned, together with providing project management in accordance with GAMP4 recommendations and standard validation templates. Every Eurotherm instrument within the package has built-in 21CFRPart11 functionality, making validation a simple process.
The company can provide supporting documentation for presentation to the quality manager. Also, whatever the scale of the system, it is based on a set of modular, standard functions. These can be easily replicated, again simplifying the validation process.
High availability is ensured as BMS/EMS provides secure plant data monitoring facilities anywhere, from a local display on a recorder through to complete plant visualisation on a web browser. This data visualisation is present on different display groups, from inputs only through room display level to the global plant level. Security is maximised as the solution stores files locally and/or centrally.
Because of its flexibility, BMS/EMS provides a scalable solution, from a single room to a plant-wide system. As a result, the project can start small, with one or two rooms, and grow to a global or plant solution step-by-step. As the system expands, Eurotherm provides robust industrial solutions that, it says, maintain backward compatibility with earlier versions – unlike many others on the market.
The pharmaceutical industry has been quick to seize on the advantages offered by the BMS/EMS package. One such company is Roche, where a system is currently being implemented. It has been designed to monitor the temperature and humidity of refrigerators, freezers and the rooms themselves within three specific areas, where the ambient temperature for storage of products must be strictly maintained within specific parameters. In the event that the temperature fluctuates outside these parameters, an alarm automatically passes to the operator.
The project is based on three Eurotherm 6180 recorders, which collect the data via the Scada (Eurotherm operation server) from the different areas within the unit for storage on Roche’s main system. As is the case with all Eurotherm equipment, the system is validated to meet GAMP4 requirements and complies with the 21CFRPart11 document for electronic records and signatures.