Computerised control systems

All major chemical companies, and most teaching establishments, now have a computerised stock-control system which enables information about on-site availability and cost of chemicals to be rapidly obtained. Many companies are now linked to a central database (e.g. Chemquest , Pergabase Inc.), which provides information (via text or graphics) on the world-wide commercial availability (from over fifty chemical catalogues) and on relative costs, etc., of fine chemicals. The hazards in use and disposal of all chemicals (see Section 2.3) may be readily checked from the catalogues of major chemical suppliers and other important sources. 

As technology progresses the safety of man-machine systems depends more and more on the quality of the human component (operator). This fact is very obvious in transportation, where the operator (driver) is formally and actually in control of his or her vehicle. In aviation, however, a strong trend towards software control of the aeroplane is already becoming dominant, forcing the operator (pilot) primarily into the role of supervisor or monitor of the automatic control system and into that of trouble-shooter in case of (technical) failure. In this respect a cockpit crew is facing the same situation as for instance a shift of operators in the central control room of a completely computerised chemical process plant. 

The control system for operating the instrument and computerised data analysis. 

Thanks are also due to the company of Switchgear Instrumentation Ltd in the UK for kindly allowing me to use some of their material pertaining to computerised management systems for switchboards and motor control centers. 

The need for computerised support systems is increasing as a result of the growing complexity of agronomic and technological variables. In a survey carried out in the USA (Stoller et al., 1993), the availability of these computerised systems was considered to be a priority for contractors, who are the key personnel in the management of weed control at ground level. 

The main control room accommodates an operator console, a supervisor s console, safety consoles, the wall panel information system large screen displays and the DAS panel. The operator console provides the displays and controls to start up, manoeuvre, and shut down the plant, and it is designed to be staffed by one to six operators. The operator interfaces are the duty system control displays, soft controls, alarm presentation system displays, computerised procedures displays, as well as the VDU monitors, keyboards and mice. The supervisor s console is a smaller version of the operators console, and is designed to be staffed by one or two personnel. The primary dedicated safety panel and VDU-based safety system workstations are located at the centre of the operator console, with a secondary safety panel located in close proximity to the supervisor s console. The DAS panel is located at a sidewall in the main control room. The main control room also includes communication devices, document lay down areas, printers and storage space. A meeting table is provided and equipped with a VDU-based workstation to allow access to the duty control system by, for example, a technical advisor or shift manager, without disrupting control room operations. In close proximity to the main control room are the shift supervisor s office, the operations staff area, an operations woik area, restrooms, and kitchen facilities. 

Overall process control. Decaffeination plants provide an ideal application area for computerised control. The control system can signal to the operators when each step should be taken and what this step should be. This results in a considerable reduction in operating costs and allows the complete plant to be operated by as few as 3 or 4 operators per shift. Even so, labour costs account for between 25 and 40% of the variable costs. 

This system includes measures and activities to control finished products, components, including water or gases that are incorporated into the product, containers and closures. It includes validation of computerised inventory control processes, drug storage, distribution controls, and records. 

The Sikarex safety calorimeter system and its application to determine the course of adiabatic self-heating processes, starting temperatures for self-heating reactions, time to explosion, kinetic data, and simulation of real processes, are discussed with examples [1], The Sedex (sensitive detection of exothermic processes) calorimeter uses a special oven to heat a variety of containers with sophisticated control and detection equipment, which permits several samples to be examined simultaneously [2]. The bench-scale heat-flow calorimeter is designed to provide data specifically oriented towards processing safety requirements, and a new computerised design... 

PEFC) stacks, components and entire systems, in off-grid, and grid-connected configurations, with a capacity of up to 100 kW electrical power output. The facility consists of an automated and computerised fuel cell test station, gas analysers, a multi-axial vibration system which is housed in a walk-in environmental chamber (for controlling temperatures, humidity, shocks and vibrations) and ancillary equipment. The data obtained are complementary to and validate fuel cell simulations and models with reference to operation modes, components and system characteristics 1 ... 

The basic principle of the method is simple. A cohort of patients with the disease in question is identified, and then a cohort of patients without the disease (usually two to three times as many) is matched with respect to a number of critical characteristics and used as the control group. Differences between the two groups with respect to exposure to the suspected causative agent are then measured. A major advantage is that uncommon or rare conditions are accessible to study, which is not the case for cohort studies or for computerised systems, where the total number of patients available is less than the several millions that might be needed. 

In central randomisation the randomisation process is controlled and managed from a centralised point of contact. Each investigator makes a telephone call through an Interactive Voice Response System (IVRS) to this centralised point when they have identified a patient to be entered into the study and is given the next allocation, taken from the appropriate randomisation list. Blind can be preserved by simply specifying the number of the (pre-numbered) pack to be used to treat the particular patient the computerised system keeps a record of which packs have been used already and which packs contain which treatment. Central randomisation has a number of practical advantages ... 

The full range of process maloperations, including system failures that might lead to process runaway will first have to be considered by a systematic evaluation of the plant and process concerned141. These may, for examplel be due to human error, hardware failure, or due to failure of a computerised sequence controller. To assess the likely/ credible maloperations accurately, it is recommended that personnel who will be operating the plant are involved in the hazard assessment. 

Japanese Ministry of Health and Welfare (1993), Guideline on Control of Computerised Systems in Drug Manufacturing, Manual for Control of Computerised Systems in GMP, Audit Manual for Manufacturers of Pharmaceutical Product with Computer Systems. 

Medicines Control Agency (MCA) (2002), Rules and Guidance for Pharmaceutical Manufacturers and Distributors 2002, Annex 11 Computerised Systems. 

Medicines Control Agency (2002), Top 10 GMP Inspection Issues, MCA Seminar — London, September 24, A.J. Trill, Computerised Systems and GMP — Current Issues. ... 

Many manufacturers have used the capabilities of on-board processing power to provide a user friendly interface for the operator. This results in a host of useful (and some not so useful) features for the analyst, and allows the pump to be remotely controlled by a computer, or another component of the HPLC system. This can facilitate method development for instance, as the pump can be programmed to change automatically the composition of the mobile phase after a number of runs. It does this by changing the proportion of time that it draws from each of a number (up to four) of solvent reservoirs, that can contain diflferent modifiers or buffers. Computerisation of pumps can also allow unattended runs to be performed with a greatly increased measure of confidence. In a networked... 

Thus, if quality is established in terms of precision and reproducibility of the results obtained in the studies (i.e. in the respective sets of measurements or experiments), the need to provide for each of the studies a study plan, approved by the head of the laboratory before the experiments or measurements can be started, will not be an important consideration. Certainly, Standard Operating Procedures will have to be observed, and the acknowledged methods will have to be followed, with any deviations to be described and justified. Since it is the quality of the result which counts for the determination of the test facility s quality , and not the way on which it has been obtained, there is no need for a single point of study control in the person of the Study Director. Certainly, a laboratory head will have to be appointed, who has to ensure that the quality of the data obtained in the laboratory remains high, and who has to provide the necessary education and training for the technical personnel in order to enhance and update their technical expertise. If precision and reproducibility are the primary purpose of the test facility s quality concerns, then apparatus, instruments, equipment and computerised systems have to comply to the highest technical standards in terms of validation, maintenance and calibration. 

According to the definition given in the Consensus Document a computerised system consists of a group of hardware components equipped with the appropriate software. Hardware on the one hand is defined as the physical parts of the computerised system, including the computer unit itself and the associated peripheral components. Software on the other hand means the pro-gram(s) that control the operation of the computerised system. The combination of these two components enables the system to perform a specific function or group of functions. All GLP Principles which apply to equipment therefore apply to both hardware and software. Figure 20 provides for a schematic representation of the interrelations of the various components within the term computerised system . 

Suitability for the intended use is something else that holds for a number of apparatus, equipment, facilities etc., and is certainly not a specific aspect of computerised systems. Computerised systems, as any other apparatus or instruments, should be of appropriate design, adequate capacity and should be suitable for their intended purposes. In the same way as for other apparatus, procedures have to be developed and documented to control and maintain computerised systems, and these systems should be developed, validated and operated in a way which is in compliance with the GLP Principles. The key word in this sentence is validated , and this term returns in the list of responsibilities of the Study Director, who has to ensure that computerised systems used in the study have been validated . This translates into the requirement that only systems that have been proven to be GLP compliant should be used in GLP studies, and the Study Director is consequently held responsible for ensuring that these systems have indeed been validated. In order to be able to fulfil this obligation the Study Director has to be actually aware of aU computerised systems that are to be used in a study. 

All computerised systems used for the generation, measurement or assessment of data intended for regulatory submission should be developed, validated, operated and maintained in ways which are compliant with the GLP Principles. Appropriate controls for security and system integrity must also be adequately addressed during the whole life cycle of any computerised system. 

Of course, not every piece of equipment can be placed into one of these two categories, and there are many possibilities in between the two of computerised systems of varying complexity. When apparatus or instruments either contain microprocessors enabling the system to process or transfer raw data, are controlled by an external computerised system, or transfer data to a computerised system for processing, then a more elaborate suitability testing may have to take place, in the extreme all the way through to a full prospective validation. 

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