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High-precision diaphragm pumps for vaccine production
Since the start of the SARS-CoV-2 pandemic, numerous countries around the world have been researching new vaccines against the virus under high pressure. The Italian branch of a U.S. pharmaceutical company will also be involved in the mass production of the vaccine and is preparing for this. There must be no dosing errors or fluctuations when the substances used are conveyed. In addition, dosing must be very pure and without any contamination. To achieve this, the company needed high-precision, low-pulsation pumps that were hermetically sealed and certified to ATEX standards. At the same time, the time for manufacturing and delivering the pumps was very tight. For this, the inoculant producer turned to LEWA-Nikkiso Italy S.r.l., a subsidiary of the German LEWA GmbH based in Leonberg. The pump expert, experienced in international GMP standards, has been manufacturing special pumps for the pharmaceutical industry for over 25 years. Therefore, the hermetically sealed Ecodos model in the steam-cleanable and FDA-compliant version in LEF3 and LEG3 sizes with explosion protection was quickly found to be the right solution. Thanks to the combination of three pump heads each with a precisely controllable motor, particularly low-pulsation pumping is guaranteed. The pressure-stiff delivery characteristic of the pumps used ensures good reproducibility of the fluid quantities, especially in the critical, low capacity range below 30 percent.
Despite some successes in the fight against the Corona virus, research and the use of suitable inoculants are still a priority. To ensure that these can be produced reliably and in sufficient quantities, the appropriate technical equipment, such as hygienic and precise pumps, is required depending on the production method. The Italian branch of a US company is now planning and supporting the further mass production of an inoculant in conjunction with a major international pharmaceutical group and required the appropriate equipment for this. Specifically, organic active ingredients were to be gently and safely conveyed from a bioreactor together with carriers such as heptane and ethyl acetate for the further chromatographic purification process. The pumps used here had to be hermetically sealed and, on the other hand, ensure a constant and precisely adjustable flow rate. In addition, because of the use of solvents, an ATEX-compliant pump type was required. The total time for manufacturing and delivery of the units was also very tight, as the manufacturer wanted to start production of the vaccine as soon as possible.
In view of these high requirements, the company commissioned the Italian subsidiary of LEWA GmbH as a reliable cooperation partner. The pump expert has been active in the pharmaceutical industry for over 25 years and has extensive experience in GMP (Good Manufacturing Practice) production areas as well as in the special requirements of the U.S. Food and Drug Administration (FDA), which the pumps also had to meet. The agreed delivery date is mid-December 2020.
Pulsation-free pumping thanks to multi-head system
“When asked which pump type was best suited for this application, the decision was made in favor of the Ecodos model, which has been used successfully by leading pharmaceutical companies for many years. The hermetically sealed pump with quadruple PTFE sandwich diaphragm and diaphragm rupture monitoring is a guarantee for absolute pumping reliability, making it the first choice for inoculant producers.”
– Stefano Biolcati of LEWA-Nikkiso Italy S.r.l.
To meet the client’s request for a combination of different pumping capacities of 3600 l/h as well as 1500 l/h, LEWA’s team designed a set of two Ecodos pumps of class LEG3 and one pump of class LEF3. Since the active ingredients used also have to be pumped with as little pulsation as possible in order to avoid mixing errors, the pumps were designed in the triplex variant, i.e. with three pump heads per pump and motor. This design ensures that the pause intervals during metering remain very short with regard to longitudinal mixing. This made it possible to dispense with additional pulsation dampeners, which due to their design would have meant problematic dead spaces in terms of backmixing and cleaning.
“What now had to be taken into account was, on the one hand, that the aggregates transport sensitive active ingredients for further purification in the liquid chromatography process and, on the other hand, that the carriers heptane and ethyl acetate have solvent properties that require specific attention,” Biolcati explains. “Therefore, gentle and stable conveying had to be ensured even in the low capacity range.” Here, the Ecodos models offer good suction behavior with a small NPSHr value, so that cavitations do not occur even with carrier fluids with low viscosity, such as volatile solvents. In addition, the organic substances originating from the bioreactor are conveyed particularly gently, as the shear effect in the pumping process is very low. The inoculant is later obtained from these in the chromatography process step.
Wide adjustment range and high precision
“An additional requirement was the need for extremely precise metering over a wide capacity range,” Biolcati reports. “Especially with the Ecodos pumps, the flow rate can be kept constant here with a maximum deviation of +/- 1 percent using the controllable motors over the speed.” In combination with the pressure-stiff delivery characteristic, a precise and reproducible flow rate is guaranteed even with fluctuating back pressure. In this way, fluids are metered accurately to the milliliter and, moreover, conveyed in sufficient quantities for comprehensive production of inoculants. If an adjustment to the composition of the vaccine should become necessary at a later date, or if a larger volume of vaccine is simply to be provided, the required fluid quantities can be easily changed in this way.
Last but not least, the pumps had to enable a sterile manufacturing process and meet hygienic production requirements to rule out impurities or contamination of the fluids. Thanks to its compact design optimized for steam cleaning, the Ecodos variant also takes into account the difficult conditions in the GMP environment.
Delivery of the pumps in time for the start of production
Despite the special requirements placed on the pumps, LEWA was able to complete the order on time with delivery to the pharmaceutical company. “Thanks to the enormous commitment of the team and the efficient inclusion of individual standard components approved for the pharmaceutical industry, it was possible to achieve this ambitious goal,” Biolcati concludes. “We are very proud to have made this small contribution to the global fight against the pandemic.” Since January 2021, the new units have now been in successful operation without any failures.
News Operation & Maintenance Processing Technologies
Stabilization of plastic exhaust systems during implementation
According to the exhaust specialist ATEC from Neu Wulmstorf, the Vario roof flange can be mounted on all roofs with high fitting accuracy. The selection is based on the roof pitch and the required nominal size. In addition, the flange is suitable for temperature classes T200 and T250 – and ATEC has had this certified with a general design approval.
The new product combines two components: first, the flange itself, which provides a stable connection between the roof elevation and the roof structure, and second, the optional seal, a self-adhesive vapor retarder. The company provides two versions: for roof pitches between 0° and 30°, and from 30° to 60°, each in eight nominal sizes between DN60/100 and DN250/315. It is also compatible with plastic and metal exhaust systems up to a nominal operating temperature of ≤ 250 °C.
The flange consists of a stainless steel clamp to which two retaining lugs/articulated brackets are welded at the factory. This is accompanied by a cover plate measuring 450 x 450 mm and 0.5 mm thick. With the help of malleable perforated strips, the exhaust pipe together with the Vario roof flange is screwed into place. This allows the Vario to be used flexibly both in new buildings and in existing properties.
News Operation & Maintenance Processing Technologies
Modern user interface impresses international jury
SIG’s new intuitive Human Machine Interface (HMI) “SIG CRUISER” has been awarded the prestigious iF DESIGN AWARD 2022 in Gold – one of the most important design awards in the world. This part of SIG’s next-generation filling technology enables customers to easily control their entire production process. The user interface is designed to make the operator’s job much easier, while reducing the need for training and prior experience.
The award has been presented annually since 1954 by the iF Industrie Forum Design for outstanding achievements in product design. The company impressed the 132-member jury, which is made up of independent design experts from around the world, and won the award in the “User Interface (UI)” category. Out of nearly 11,000 entries, SIG CRUISER was awarded gold as one of 73 outstanding design achievements.
The judges made the following statement, “With a user-centric approach and sound development methodology, SIG CRUISER provides consistency from the store floor to the top floor, ensuring quick response times and convenience for both the operator and the service team. The user interface is exceptionally simple and user-friendly in terms of operations, layout and graphics, allowing a single operator to control the entire line.”
Today’s competitive environment requires companies to increase production and margins and optimize available equipment. To get the most out of filling lines, it is critical to reduce the risk of downtime and to interconnect, automate and monitor lines for maximum efficiency. The new user interface makes it possible to control the entire filling line. It displays KPIs in an intuitive way.
“This prestigious global design award is the result of the good cooperation between SIG and our partner, HMI Project GmbH. We are very proud that SIG CRUISER stood out from thousands of submissions and convinced the 132-member jury to award an iF DESIGN AWARD in Gold.”
– Stefan Mergel, Senior Product Manager Equipment
Ingredients & Auxiliary Materials News Pharmaceuticals Processing Technologies
Innovative insights into emergence and classification into subtypes
One of the deadliest tumor types is pancreatic cancer . The disease is often only discovered in locally advanced or metastasized tumor stages, when surgical intervention comes too late. Researchers led by Dr. Ivonne Regel of LMU Klinikum in Munich have now gained important new insights into the causes of tumor development. They have also succeeded in defining different tumor subtypes based on differences in their metabolic programs. Funded by the Wilhelm Sander Foundation, they are thus making a significant contribution to early detection and to individualized medicine in order to improve the chances of recovery for pancreatic cancer patients.
Pancreatic ductal adenocarcinoma, also known as pancreatic cancer, is a relatively rare but particularly malignant disease. It represents the fourth leading cause of cancer-related deaths in the European Union, and only about 10 percent of patients survive the first five years after diagnosis. This is due to aggressive growth and late diagnosis of the tumor. Pancreatic cancer often manifests itself only after other organs have already been affected and metastases are present. To improve the chance of cure for pancreatic cancer patients, it is of great urgency to find new biomarkers for early detection. Another essential step is to identify tumor-specific signaling pathways that cause aggressive disease progression in order to identify new targets for therapeutic approaches.
TLR3/IRF3/IRF7 signaling pathway critical for pancreatic cancer development
Pancreatic cancer development is a dynamic process involving tissue damage and inflammatory response in the pancreas. When pancreatitis occurs, the organ has a self-healing mechanism. Normal pancreatic cells can divide to replace damaged tissue. Molecules released during inflammatory and tissue-damaging processes are recognized by cell receptors, relaying signals that promote cell survival and division.
However, in pancreatic cells, this can contribute to cell degeneration and promote the development of pancreatic cancer. Researchers led by Dr. Ivonne Regel were able to show for the first time that the signaling pathway plays an important role in inflammatory responses not only in immune cells, but is also active in pancreatic cells of precursor lesions and tumor cells. This activation of the signaling pathway has an important function in pancreatic cancer development. Genetically-altered mice lacking a functional signaling pathway are unable to develop pancreatic carcinomas (see Figure). Similarly, it was genetically knocked out in pancreatic tumor cells using CRISPR/Cas9 gene scissors. These genetically modified tumor cells exhibited significantly less aggressive behavior in cell culture experiments and also showed greatly reduced metastasis in animal models.
“For the first time, we were able to demonstrate that an active signaling pathway in pancreatic cells contributes to the development of pancreatic cancer and also supports the formation of metastases.”
– Ivonne Regel
Dr. Regel’s team has made another exciting discovery: In pancreatic tumor cells, the signaling pathway surprisingly does not regulate known target genes; instead, evidence was found for epigenetic modifications. These are regulatory modifications to DNA and packaging proteins (histones) that influence the activity of genes. Thus, the current research results indicate that activation of the signaling pathway in tumor cells leads to high levels of transcription of specific tumor-promoting genes.
These genes primarily regulate tumor cell metabolism. This is particularly important because metabolites of tumor cells can be found in the blood of patients and can be used as biomarkers. “My team and I have succeeded in identifying different subtypes of pancreatic cancer from the blood of cancer patients based on differences in their metabolic programs” said Dr. Regel. “In further studies, we now want to find out to what extent the development of pancreatic cancer subtypes is regulated by the signaling pathway.”