“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.”
FDA 21 CFR Part 820.70 Production and Process Controls, section c.
Control and monitoring of storage and production environments has become an important issue within the Pharmaceutical Industry. The FDA, EMEA and other regulatory bodies require accurate measurement and storage of room parameters and, if the storage medium is electronic, the methods used must comply with FDA 21 CFR Part 11.
The FDA also states in its 21 CFR part 203.32 that:
“Manufacturers; authorised distributors of record and their representatives shall store and handle all drug samples under conditions that will maintain their stability, integrity and effectiveness and ensure that the drug samples are free of contamination, deterioration, and adulteration.”
Other FDA rules related to environmental control and monitoring include:
The Eurotherm BMS/EMS system is designed to satisfy the requirements of regulatory bodies including FDA 21 CFR Part 11 and it offers:
Eurotherm Building Management Systems provide control, monitoring, recording and alarming of a range of facilities within a plant including:
Not all existing BMS systems offer a logging facility and, for these systems an independent monitoring system, EMS, will be needed. Typically an EMS will provide independent
monitoring and logging of the critical environmental parameters for GMP, GLP and GDP facilities.
Eurotherm BMS/EMS Standard Modules
Eurotherm BMS/EMS solutions are modular and scalable. They offer all the functionality required to control, monitor, record and alarm, for a single room to a plant wide application.
They are ideal for
It offers the options for:
Sensors communicate measurement and status information from the process to the control and monitoring modules of the BMS/EMS system. Sensors include:
For hazardous rooms intrinsically safe devices must be used including:
Eurotherm can offer a range of the above sensors or alternatively provide interface to sensors supplied by the user.
BMS/EMS offer a wide range of options for monitoring the plant. Information can be monitored locally, centrally and remotely. Access to the system is protected. Users must login to gain access to functionality, defined by their access level.
Plant information is monitored through standard and custom displays and includes:
Information received from the plant is grouped together in various forms to allow the users to rapidly access the required information. The system utilises an easy to use, hierarchical methodology of presenting the necessary information to the users including:
Data collected from the plant are linked together and displayed as trends using online and historical trending within the system.
Trended data are available in various groups e.g. by room, by type (temperature, pressure etc.) The monitoring facility also provides the user with access to standard features of the system according to their access level, including:
The purpose of this component is to provide the control of the necessary parameters for each individual room/area. It offers standard control functionality, e.g. PID loops, to accurately control the various environmental conditions of the room.
It also provides the functionality required to control devices such as pumps, motors and valves, e.g. start/stop with necessary interlocks. Operation can be configured to be automatic, semi-automatic, manual or any combination of these.
Individual rooms/areas may be operated in different modes; the selecting of which is access controlled by authorized users:
BMS offer the facility for adjusting control parameters (e.g. setpoints, alarm limits, tolerances, time delays) in order to achieve the desired condition in each room. This feature is only available to users with the appropriate access permissions. The system provides a full audit trail of these changes including electronic signatures.
Data logging is a key requirement for BMS/EMS systems. FDA 21 CFR Part 11 requires that logged data will be tamper proof and will include critical environmental parameters
(temperature, humidity, pressure, particulate sizes, etc), with audit trails including:
Eurotherm’s BMS/EMS systems log plant data to tamper proof files and SQL relational databases. Data logging can be offered as:
The availability of logged data can be significantly increased by the local and central logging option. This allows data collection in multiple devices to further protect vital plant data.
Typically a BMS/EMS system comprises of a number of distributed units where each unit has its own internal clock. Time synchronisation is included to ensure accurate time and date stamps, as required by FDA 21 CFR Part 11, to a known clock source.
The BMS/EMS system offers provisions for electronically copying data for archive and export facility to common packages (e.g. Excel, Word, PDF, etc.) for viewing of secure records in human readable format. Other features of the system include:
The system can be configured to provide logging for non-critical parameters including:
An important feature of the BMS/EMS system is its Alarms and Events functionality. All alarms and events are time stamped and logged for long term retention and validation to FDA 21 CFR Part 11. Individual plant data can be configured to have one or a combination of the following alarms:
The system can be configured to provide other alarms including;
Alarms can be configured as critical, non-critical or as an Event. Critical alarms will require manual acknowledgement and non-critical will be auto-acknowledged. Alarm selection and setpoint settings are available to the users with the appropriate access level and critical alarms can be configured to require an Electronic Signature for changes. Alarm acknowledgement and all changes to alarm settings are automatically logged as required by FDA 21 CFR part 11. All alarms and events are reported through local, central, and remote HMI panels. They are displayed in the Alarm Summary and Alarm History pages which provide a sort facility for the information. Alarms can be grouped by their criticality and function to ensure individual alarms can be quickly accessed.
Other features of the BMS/EMS alarm system include:
Review and Reporting
The BMS/EMS system provides a comprehensive review and reporting system. The system offers two methods for collecting data:
These methods may be combined and, in both cases, the system provides the facility to create reports for individual rooms. A number of standard report templates are provided along with the facility for users to create their own reports.
Information can be automatically transferred and accessed from standard Microsoft® Office packages.
Security Manager offers significant operation cost savings and ease of use by allowing maintenance of user accounts and passwords from one or multiple locations. If a user needs to change their password they can do so on a local instrument or PC and this will be automatically distributed across all systems to which they have access.
Maintenance is an essential part of any BMS/EMS system. Maintenance information on various elements of the system (e.g. last calibration date, calibration due date, last maintenance date, maintenance due date) is shown on multiple displays throughout the system. The system can provide warnings if calibration/maintenance dates for individual equipment are approaching and/or exceeded.
Access permission can be given to individual users to select maintenance modes for the following:
Maintenance mode can also be selected for a given area e.g. a room or a zone of the plant. While in maintenance mode the individual equipment or area will be clearly identified on the display using colour and text. The system can be set to suppress alarms and stop logging parameters for associated equipment at this time.
Selection and the de-selection of the maintenance mode will be logged as an event in the audit trail.
Easy to use calibration tools are included in the system for use during maintenance mode. Selection and de-selection of the calibration mode is logged in the audit trail.
Remote Alarm Notification
Nominated users can be quickly notified of alarm conditions via the telephone system.
The system offers:
Remote users, including off-site, can access plant information via a secure web portal.
Services need to be provided from the beginning of the project, though the project development and commissioning, and for the lifetime of the system.
Eurotherm offers a complete range of services such as:
A key requirement for BMS/EMS solutions is validation. Where environmental conditions (e.g. temperature, humidity, differential pressure, air flow, sterility, containment) have a direct impact on product purity, safety, quality or efficacy they need to be monitored against predetermined limits and logged. In this case the BMS/EMS system used for collecting and logging the data needs to be validated. According to ISPE guidelines, it is good practice to monitor the performance of equipment such as fans, coil and control components, but it is not a regulatory requirement.
Validation documentation needs to be provided through the cycle of the BMS/EMS system. Eurotherm can offer a range of documentation services following ISPE GAMP5 guidelines and in accordance with customer requirements:
Measurement and recording of temperatures is vital to the storage of perishable goods, but there is more than one way to record an average. The ICH defines the mean kinetic temperature as being “A single derived temperature that, if maintained over a defined period of time, affords the same thermal challenge to a drug substance or drug product as would be experienced over a range of both higher and lower temperatures for an equivalent defined period”.
MKT expresses the cumulative thermal stress experienced by a product at varying temperatures during storage and distribution. It differs from other means (such as a simple numerical average or arithmetic mean) in that higher temperatures are given greater weight in computing the average, recognising the accelerated rate of thermal degradation of materials at higher temperatures.
Eurotherm minimizes the implementation and operation cost of providing MKT data by making all of the above methods as integral part of our solution with: