Bioprocesses are used to manufacture products in which one or more biotechnological techniques are applied. Living organisms, or their products, are used to modify living or non-living matter for the production of goods. Application areas include the production of bacterial and viral vaccines, toxoids and similar products, such as allergen extracts, sera, plasmas and other blood derivatives, for human or veterinary use.
GMP ("good manufacturing practice") compliant production and the avoidance of any risks for the consumer of the end product have the highest priority. Measurement technology from WIKA delivers process-specific information which enables high-quality production. For this, the safety, the hygienic requirements in the design of the measuring instruments and the connection of the sensors to the bioprocess equiptment are fulfilled optimally. Via the global sales and service network, experienced employees are always available to our customers for the selection and commissioning of our instrumentation solutions and also for calibration and maintenance operations.
The pharmaceutical vessels can be used for a variety of different purposes. Among other things, they serve as preparation vessels, buffer tanks, mixing tanks, intermediate tanks or for harvesting or inactivation. Depending on the application, the tanks are fitted with insulation as well as heating and cooling jackets and, if necessary, a stirrer. The diverse tasks of the tanks require a measurement technology to match. WIKA offers a wide range of hygienic instrumentation for level measurement, overpressure and temperature monitoring in the tanks.
The upstream process starts with thawing a vial from the cell bank and adding it to a small amount of medium, prepared in the media and buffer-preparation area of the production facility. The cells are then cultivated in bioreactors, under conditions that are optimal for them. Gradually, the cells are transferred to larger bioreactors with growth medium. This process is repeated ("scale-up") until the final volume of the bioreactor is reached. Some of the largest final volumes are 20,000 litres and more. Due to the huge costs associated with scale-up, it is important to understand the impact of process variables such as temperature and pressure.
WIKA offers specially developed instrumentation for the various process parameters around the bioreactors in the upstream process. These are, for example, level measurement with foaming media or overpressure and temperature monitoring, both in the bioreactor and for the heating jacket.
Using a centrifuge or separator, the cell culture medium is rotated at high speed and centrifugal force is used to separate the mixture into its denser and lighter components. With the aid of pressure sensors, the inlet and outlet can be monitored and thus the separation performance optimized.
For the process equipment used during purification, such as separators, chromatographs and filters, WIKA has a range of in-line instrumentation that can be integrated optimally into the pipework in accordance with hygienic design requirements.
Filtration is an important part of the manufacturing process with the aim of product purity. A number of different filtration processes take place during the downstream process. An important quality aspect here is filter monitoring using differential pressure. This makes it possible to detect a filter perforation in good time or to determine when the filter cartridge needs to be changed.
For the process equipment used during purification, such as separators, chromatographs and filters, WIKA has a range of in-line instrumentation that can be integrated optimally into the piping in accordance with hygiene requirements.
In bioprocesses, it is common to use liquid chromatography for purification in the downstream process, to separate proteins or biomolecules. The inlet and outlet from the chromatography column can be monitored and adapted optimally to the process with the aid of in-line instrumentation. For the process equipment used during purification, such as separators, chromatographs and filters, WIKA has a range of in-line instrumentation that can be integrated optimally into the piping in accordance with hygiene requirements.
Mobile tanks serve various purposes in the downstream process:
Particular attention is paid to ensuring that the storage and transport conditions of the process liquids are monitored and complied with. These include, in particular, temperature monitoring and leakage monitoring using the pressure drop method, for which a range of instrumentation is available. Even if the vessel should be completely autoclaved, WIKA has developed special measuring instruments for this purpose that withstand the process conditions of autoclaving. Autoclaving is a sterilisation procedure in which items or equipment are sterilised in saturated steam for at least 20 minutes.
After purification, the manufacturer formulates the therapeutic protein in accordance with the production specifications. These requirements take into account factors such as product stability and dosage form. For this purpose, excipients (pharmacologically inactive ingredients) may be used to improve the medicinal product. These can include colour additives, time release factors and fillers. In addition, substances such as antioxidants, buffers and surfactants can be added to increase the stability of the drug to reduce clumping.
For the inlet and outlet lines, WIKA has a range of in-line instrumentation that can be integrated optimally into the piping in accordance with hygiene requirements.
At the end of production, the product is filled into the appropriate vials, ampoules or syringes. It is then marked until the finished drug is packaged and made ready for shipment in bulk packs.
A range of in-line instrumentation is available for filling lines, which can be integrated optimally in accordance with hygiene requirements. WIKA offers a comprehensive range of measuring instruments for the monitoring of ventilators and blowers, overpressure monitoring for isolator, RABS and clean rooms, temperature monitoring on heat exchangers, measuring of the air flow and the air velocity in air ducts and air-conditioning systems.
CIP ("Cleaning in place") is an automated cleaning process for process equipment and machinery. All surfaces in the system that come into contact with the product are cleaned without disassembling the system or dismantling essential components.
The key process steps of a CIP cleaning are:
The hygienic design of process equipment in contact with products is a prerequisite for CIP and serves to avoid microbiological contamination, and with that, ensuring product quality. WIKA offers a comprehensive programme for the integration of measuring instruments for CIP cleaning as well as instrumentation specifically adapted to the caustic and acid tanks - in corrosion-resistant special materials.
SIP ("Sterilise or steam in place") is a time-controlled sterilisation for both the upstream and downstream processes in biopharmaceutical production using pure steam. It is part of a disinfection routine that is carried out after each production batch. It follows the CIP process ("clean in place"). During SIP, care must be taken to ensure that all wetted surfaces in contact with the product are sterilised by the condensing saturated steam. Thus, no air bubbles in any branches or dead spaces should prevent the steam from wetting the surfaces to be sterilised.
WIKA's in-line instrumentation, which can be optimally integrated into the SIP lines in accordance with hygiene requirements, reduces the risks of any dead space and thus contamination. For the highest demands, WIKA has sensors with integrated self-monitoring that immediately signal if the parts in contact with the product are damaged. A wide range of instrumentation is also available for the plant steam in order to monitor the steam precisely.
Water for injection (WFI) must meet the strictest hygiene standards. It is produced by filtering and distilling drinking water. This purification process leads to a significantly lower germ-load than with tap water. The WFI is circulated constantly via a high-temperature circulation line (65 to 80 °C) to maintain circulation at all points of use of the WFI system. This minimises the possibility of microbial contamination. The specification of the water used as an ingredient for drugs, and for cleaning, must comply with the currently specified quality requirements in accordance with the applicable standards.
WIKA's in-line instrumentation, which can be optimally integrated into the WFI lines in accordance with hygiene requirements, reduces the risks of any dead space and thus contamination. For the highest demands, WIKA has sensors with integrated self-monitoring that immediately signal if the parts in contact with the product are damaged.
Precise calibration instruments are the starting point for resolving your test requirements. However, they only form one part of a high-performance calibration system. From our extensive product range, we can design a complete and individual solution for you which contains all the relevant components – with adaptability for test items, pressure and vacuum supply, components for pressure control and fine adjustment, through to voltage supply and multimeters for the calibration of electrical test items.
Our particular strength lies in the project planning, development and the building of complete, individual, user-specific systems – from simple manual workstations through to fully automatic test systems in production lines.
Are you looking for suitable calibration equipment for your applications? Get an overview of our wide range of calibrators. In addition, use our calibration service for pressure, temperature, force, flow and also electrical measurement parameters. We calibrate your references and test equipment independently of manufacturers in our accredited calibration laboratories, or directly on your premises.
WIKA supports you with additional services – our experts are at your disposal. Service technicians will make sure that your measuring instruments, in case of breakdowns and repairs, are fully functional again in a short space of time. From pressure controllers and diaphragm seal systems to calibration baths – you can get everything from us in the one place. Furthermore, we install your measuring units and provide you with support in the commissioning of the instrumentation. Through our local experts, we can be reached worldwide, are quickly available and tuned to individual circumstances. Try it for yourself.