Invasive temperature measurement in pharmaceutical processes
In pharmaceutical processes, besides time, temperature is one of the most frequently measured physical parameters. Depending on the drug to be produced, far more than 50 % of all measuring points in a production plant are temperature measuring instruments.
Temperature plays a central role in many processes. For example, the growth of the cells during fermentation depends significantly on the process temperature. If the temperature is too low, the gain is limited; if it is too high, the cells may die. The complete batch would then have to be abolished, which would cause a loss of several ten thousand Euros. Therefore, it is important that the temperature is measured with high accuracy at the quality-relevant measuring points.
In order to guarantee that the accuracy of the measurements permanently remains constant and does not differ, the measuring instruments are calibrated at regular intervals. The measuring instrument is compared to a reference standard and it is evaluated whether the measuring deviation of the test item still is within a tolerable range. How often which measuring instrument is calibrated depends on how far the measurement affects the quality and safety of the production process. The calibration intervals can be up to 2 years, but for critical processes, they can be considerably shorter. In severe cases the measuring instrument is controlled after each batch.
The pharmaceutical manufacturers must observe the requirements and regulations of the different authorities. The Food and Drug Administration (FDA) plays an important role. The agency within the U.S. Department of Health and Human Services monitors hygiene risks and the quality standards of the drug manufacturers. Principles and guidelines for the safe production and for compliance with the quality standards arise from the European GMP regulations. The essence of the regulations for measuring instruments is that they must not have any negative impact on the quality and safety of the processes and that they consequently have to be calibrated at regular intervals.
Therefore, the electrical thermometers developed by WIKA are all designed in such a way that they can be easily calibrated on site. The thermowell stays in the process and keeps the process closed so that it is not contaminated from outside. The connection head can be pulled out of the thermowell together with the measuring insert and it can be calibrated directly on site at the measuring point by means of an accordingly designed WIKA dry well calibrator. This makes it possible to calibrate the resistance thermometer (the sensor, the temperature transmitter and the measuring line to the control system including the cable connections) together with the whole measuring chain, i.e. without having to disconnect the electrical connections. A precondition for this is a suitable control system, which enables an on-site calibration. If such a control system is available, the measuring instruments can be calibrated quickly and without much effort directly in the plant. This saves the plant manager the separate calibration of electrical line and sensor as well as the time-consuming insertion and removal of the measuring instruments into/from the clean rooms. Additionally, the number of replacement sensors is kept low. This maximises the availability of the plant and at the same time minimises the costs and the deployment of personnel.
Another aspect of safe and reliable temperature measurement is the consequent application of the hygienic design for the temperature measuring instruments. As the FDA as control authority for pharmaceutical manufacturers does not provide any standards for this, they refer to the compliance with the standards provided by 3-A Sanitary Standards Inc. In the standard for the sensors and sensor fittings and connections, important criteria are defined concerning the materials, the surfaces and the design of the measuring instruments and sensors. The compliance with the standards is checked by independent certified evaluators in a so called Third Party Verification (TPV). The TR-22 resistance thermometer and the compact TR-21 temperature sensor developed by WIKA are 3-A marked based on a third party verification for conformance to the standard 74-03.
The thermowell for orbital welding recently developed by WIKA has been highlighted for its outstanding design. By means of this thermowell, a temperature measuring point can be integrated optimally and without having to use any sealings into sterile pipeline systems. Regarding the measurement, the measuring point is designed outstandingly and is influenced only very little by the ambient temperature even in naked pipelines as they are usually found in clean rooms. The sensor registers the temperature right at the core of the flowing medium and is not influenced by the cooler surface of the pipeline as it is the case with surface sensors, for example.
Thanks to the patented design, the flowing medium keeps its optimal flow. Dead spaces, leading to deposits and cleaning difficulties, as they occur in thermowells with necks used so far, are avoided. Thus, electrical resistance thermometers which have been optimally designed in accordance with the hygienic design and can be calibrated cost-effectively are available to the managers of pharmaceutical plants.
