An immune process
In-line pressure measurement in the sterile process engineering

As a subset of process engineering, sterile process engineering is an important factor within pharmaceutical, biotechnology and food-and-beverage production. In these industries, the production, filling and packaging processes must be sterile, in order to avoid contamination by micro-organisms. To maintain this within process instrumentation requires some innovative technical solutions, which must also comply with EHEDG or 3-A regulations.

Sterile process engineering defines itself as a subset of process engineering within pharmaceutical, biotechnology and food-and-beverage production. In these industries, the production, filling and packaging processes must be sterile, in order to avoid contamination by micro-organisms.
This requirement also applies to the process instrumentation used. The widest variety of process control tasks are solved through the measurement of pressure. For example, pressure is one of the main variables used in the control of chemical and biochemical reactions; by measuring the differential pressure, the degree of fouling in filters is monitored; and in product filling, where the fill-rate is optimised through pressure measurement.

In order to meet the demand for sterility while measuring pressure, in-line measuring instruments are used. In-line measuring systems use either pressure gauges or pressure transmitters in combination with a diaphragm seal. A circular metal diaphragm separates the measuring instrument from the process medium. The inner cavity between the diaphragm and the pressure measuring instrument is completely filled with a system fill fluid. The fill fluids, which transfer the pressure of the measured media in contact with the diaphragm to the sensor, are selected in such a way that they meet the purity requirements of the FDA. By the nature of the circular internal construction, diaphragm in-line seals are self-draining in all installation orientations. Product residue can be washed away without any problem, and their design eliminates dead volumes in the process line, where bacteria could otherwise be deposited and thus contaminate the process medium.
The optimal design
In order to increase the competitiveness of production operations, processes are automated and traditional batch processes are being replaced by continuous processes. Continuous operation means that the plant has to be cleaned in-situ, without the removal of any components. This is achieved through Clean-in-Place (CIP) systems. Thus manual cleaning can be limited and down-time is reduced. Therefore pressure measuring instruments with diaphragm in-line seals can be washed internally, automatically. Flushing/rinsing is carried out with cleaning solutions such as NaOH, or H2O2 at increased temperature (to 80°C) and pressure (up to 4 bar). An effective CIP cycle requires that the sensitive measuring diaphragm of the pressure instrument must withstand repeated cycles of washing/ rinsing/draining, without any material change or leakages. Besides standard chromium-nickel stainless steel 1.4435, full-austenitic materials such as 1.4539 or further special materials such as Hastelloy are available to the user.
Sterile production conditions require the plant to be sterilised following the CIP process. So the Steam-in-Place (SIP) cycle follows the CIP cycle and is likewise carried out in a sealed system. For the sterilisation process, saturated steam conditions must be maintained at a temperature of at least 121 °C (at the coldest point of the plant) over a 20-minute time span. Currently there is a trend towards noticeably higher temperatures of up to 150°C for SIP processes.
To validate the plant across both the CIP and the SIP cycle a log must be made, from which the adherence to the process parameters can be proven. For this, a diaphragm in-line seal connected to a high-accuracy pressure transmitter is usually used.
The various standard/specific fittings used in the food, biotech and pharmaceutical industries, such as milk thread fittings according to DIN 11851 or aseptic connections according to DIN 11864, clamp fittings or those according to specific manufacturer’s standards such as Neumo BioConnect, can be easily realised with diaphragm in-line seals. When specifying the diaphragm in-line seal, special attention should be paid to ensure that the inside diameters of the process line fittings are specified exactly. In this way, cross-section oversizing or restriction is avoided with the diaphragm in-line seal and with it accompanying flow dead-spots. Furthermore, it is important to consider that, for the efficient assembly of the entire measuring system, the connections of the diaphragm in-line seals are provided with male threaded connections and that the union nut is mounted at the process line fitting.
Directives and references
International standards and directives provide the guidelines for global enterprises. They remove technical barriers to trade and guarantee technical conformance. The best-known and most important organisation concerning monitoring of hygiene risks within production in sterile process engineering is the FDA (Food and Drug administration). This US authority plays an important role through the assessments of their “Food Inspectors”. Within the scope of this examination both the manufacturing process and the technology used for it are examined. During this process the material selection, the suitability of the system fill fluid used and the calibration cycles of the measuring instruments are all put under the microscope with the associated documentation also thoroughly checked.
3-A Sanitary Standards Inc., with their Standard 74-02, provides for the composition of wetted parts for sensors and measuring instruments within the US market. Compliance with the organisation’s requirements is proven by means of Third Party Verification. Only after the successful completion of this audit may measuring instrument manufacturers apply the 3-A Logo to their instruments. All Wika diaphragm in-line seals with hygienic fittings can be marked with the 3-A Logo. Machines and components for sterile process engineering which feature a 3-A Logo can be exported more easily into the American market.
The European Hygienic Equipment Design Group (EHEDG) was founded by a number of European institutes involved with food production machinery. It expresses recommendations regarding the hygienic design of plant components and provides test methods for proving the design. They also carry out these investigations themselves and certify the devices after testing. These tests have been completed on Wika’s diaphragm in-line seals. In addition, the diaphragm in-line seals are even used for the pressure monitoring of these tests on the equipment at the Technical University in Munich/Germany, at the “Lehrstuhl für Maschinen- und Apparatekunde” in Weihenstephan. The diaphragm in-line seals are also able to fulfil other demands such as certain surface finishes (such as RA<0.8) or meeting cleanability tests. Thus the criteria laid down in EHEDG Document No.8, “Hygienic equipment design criteria”, are also fulfilled. In conclusion, the in-line pressure measuring technique meets the demands of all conditions occurring within the sterile process engineering industry.