80-GHz Radar for Single-Use Applications
Published on : Wednesday 01-09-2021
Optimal monitoring of biopharmaceutical processes with VEGAPULS radar sensors.
In the biopharmaceutical industry, single-use technology is one of the answers to the demand for more agile manufacturing processes that also meet regulatory challenges. It enables fast, seamless product changes while maintaining hygiene and optimising process costs. However, it requires a suitable level measuring system, which must be just as flexible and efficient as the rest of the single-use production equipment: 80-GHz VEGAPULS 64 radar sensors are the solution.
What are the advantages of single use?
In single-use production of active agents and biopharmaceutical products, the entire process chain consists of sterile, disposable systems. The method thus perfectly meets the increasing demands on the productivity, cleanability and flexibility of production systems. Single-use equipment offers a number of advantages in biotechnological processes as well as in sterile drug manufacturing. Compared to stainless steel systems, the costs for cleaning are greatly reduced, as is the work involved in cleaning validation. The elimination of CIP and SIP cleaning also saves valuable production space.
Single-use processes can improve time-to-market by eliminating system setup work and enabling faster scale-up. In short: This technology allows flexible production and a correspondingly flexible response to market demands.
Increased acceptance by authorities
The increasing application of single-use is increasing specialist know-how: the requirements this production method has to meet are being better and better understood. Acceptance by authorities and customers is also increasing. In view of the abovementioned advantages, the method is virtually predestined for use in the manufacturing of highly active products. This is because containment and docking between insulators and pressure vessels play a central role here. In fact, the interfaces between process and containment are particularly critical areas. But in single-use applications, this problem is easily solved: a new, sterile surface is used for each batch – completely eliminating the risk of cross-contamination.
The role of sensors in single-use production
Biopharmaceutical products do not fall into the category ‘simple’, because the list of challenges for manufacturers is long. All large, as well as small, problems can only be successfully solved if the right components are used. This also applies to the sensors that monitor level and pressure during the manufacturing process, ensuring quality and reproducibility.
A single-use reactor is usually delivered pre-sterilised, cannot be opened afterwards and must be completely disposed of at the end of the process. While single-use systems are becoming more and more sophisticated as they are used more often, there is still no consensus on which sensor technology is the best for them – indeed it remains a much-discussed topic. Although invasive measuring systems, whether in the form of built-in components or inserted probes or sensors, are totally out of the question, continuous level detection is still necessary to ensure high process efficiency.
What has to be considered? Basically, the requirements on the sensor technology here differ only slightly from those in conventional pharmaceutical applications. As in all other parts of the process, the focus is on cleanability and sterility. However, the requirements are extended to include higher sensitivity, optimised response behaviour and narrow tolerance ranges. In addition, sensors in a single-use system have to be mechanically robust and operate with as little calibration as possible. Any product contact that can be avoided increases compliance with production according to GMP. It reduces the risk of contamination of the product through cross-contamination or the abrasion of particles from contacted materials – and makes it easier to validate the safety and reliability of the system.
What measuring methods come into consideration here?
In single-use applications, it is still common practice to determine the level by weighing. However, the big disadvantage of load cells is that their measuring results are easily corrupted. This can happen, for example, if, due to irregular expansion of the flexible bioprocess bag, the parts of the bag touching the measuring system shift. Load cells used for containers that are constantly in motion also require relatively frequent recalibration.
The alternative to weighing, capacitive measurement, also has disadvantages. Capacitive sensors are often not sufficiently accurate or responsive for the small production quantities of substances that are increasingly considered ‘highly active’. They can even damage or destroy the single-use bag when they are removed. And just like with load cells, the typical irregular filling and folding of single-use bags has a negative effect on accuracy. In capacitive contact measurement, the electrode in the sensor tip, together with the GND electrode, functions as a capacitor plate; for this reason it works like an open capacitor. As a probe, it has to be inserted into the measured medium from the outside of the bag.
Special single-use sensor systems are another variant that, although convincing in terms of price, lags behind other methods in terms of reliability and accuracy. Insufficient ruggedness and durability are among the disadvantages of the available models that can adversely affect the ongoing process.
The advantages of 80-GHz radar
Continuous level measurement with 80-GHz radar technology, in contrast, reliably helps to achieve the required high process efficiency. VEGAPULS 64 radar sensors measure contactlessly from outside the process, right through the plastic container. This works even if the bag surface has wrinkles. By avoiding all contact with the medium, the danger of cross-contamination can be effectively minimised. The work involved in installation and setup is also minimal: with little or no adjustment, the high-frequency radar sensors start measuring immediately and react flexibly to process changes.
Small containers, high accuracy
Stirring and mixing in small containers with heights of less than 2 metres are typical processes in single-use applications. With an antenna size of DN50, VEGAPULS 64 has a beam angle of only 3°. This creates the strong focusing that allows the sensors to measure right past internals and deliver reliable results in such applications. What is more, VEGAPULS 64 can measure the level very close to the container bottom with an accuracy of +/- 2 mm. This is particularly advantageous for the sensor in compact applications like the standard culture bags.
The dynamic range of a radar sensor, i.e., the difference between the largest and smallest signal, is a good indication of which applications the sensor can be used in. The greater the dynamics, the wider the application range of the sensor and the higher the measurement certainty. With a dynamic range of 120 dB, the best on the market, VEGAPULS 64 can even cope with the condensate that typically forms on the inside of container bags.
What are the advantages of using multiple sensors?
Reusable sensors are the higher quality alternative for single-use applications − provided they are as easy to use as their disposable competitors. 80-GHz radar sensors can be placed outside single-use bags, while the bags themselves are coupled via special plug-in connectors.
This guarantees the necessary sterile barrier: the bags, however, remain effectively transparent to the strongly focused and highly dynamic sensor signals. VEGAPULS 64 is thus able to query the contents of the bioreactor with high precision – always with the advantage of being reusable and not in contact with the medium.
VEGAPULS 64 radar sensors can also be optimally integrated into many other sterile processes besides single-use. Their hygienically flawless antenna connections allow them to be mounted front-flush. Process fittings that use only PTFE as the media-contacting material are also available for use in hygienic applications. The materials thus meet the requirements of both FDA and EC 1935/2004. The design of the sensors complies with the specifications of the 3-A standards.