Since the start of the COVID-19 pandemic, numerous countries around the world have been working hard to develop new vaccines against the virus. A U.S. pharmaceutical company based in Italy will also be involved in the mass production of the vaccine and is preparing for it. There must be no dosing errors or fluctuations when conveying the ingredients used. In addition, dosing must be very pure and without any contamination. For this purpose, the company needed high-precision, low-pulsation pumps that are hermetically tight and certified in accordance with the ATEX standard. At the same time, the short time for production and delivery of the pumps posed a challenge. The vaccine producer turned to LEWA-Nikkiso Italy S.r.l., a subsidiary of LEWA GmbH based in Germany. The pump expert is experienced in international GMP standards and has manufactured special pumps for the pharmaceutical industry for over 25 years. Therefore, the right solution was quickly found: the steam-cleanable and FDA-compliant version of the hermetically tight Ecodos model in sizes LEF3 and LEG3 with explosion protection. Thanks to the combination of three pump heads with a common, precisely controllable motor, particularly low-pulsation delivery is guaranteed. The pressure-stiff characteristic curve of the pumps used ensures good fluid quantity reproducibility, especially in the critical, low capacity range below 30 percent.
Despite some successes in the fight against the coronavirus in various places, research and the deployment of suitable vaccines remain the focus. To ensure that vaccines can be produced reliably and in sufficient quantities, depending on the production method the appropriate technical equipment is required, such as hygienic, high-precision pumps. A U.S. company based in Italy is planning and supporting the further mass production of a vaccine in conjunction with a major international pharmaceutical group and required the appropriate aggregates for this purpose. 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 downstream chromatographic purification process. The pumps used here had to be hermetically tight and, on the other hand, ensure a constant, precisely adjustable flow rate. In addition, because of the use of solvents, an ATEX-compliant pump type was required. The total time for production and delivery of the units was very short, as the manufacturer wanted to start production of the vaccine as soon as possible.
In view of these rigorous requirements, the company commissioned the Italian subsidiary of LEWA GmbH as a reliable cooperation partner. The pump expert has worked 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 needed to meet. The agreed delivery date was mid-December 2020.
Pulsation-free conveying 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 successfully used by leading pharmaceutical companies for many years," said Stefano Biolcati of LEWA-Nikkiso Italy S.r.l. "The hermetically tight pump with a quadruple PTFE sandwich diaphragm and diaphragm rupture monitoring guarantees 100% metering reliability, making it the first choice for vaccine producers." In order to meet the combination of different flow rates of 3600 l/h as well as 1500 l/h requested by the client, the LEWA team designed a set consisting of two LEG3 type Ecodos pumps and one LEF3 type pump. Since the active ingredients used must also be metered as pulsation-free 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 dampers, whose design would have created problematic dead spaces in terms of back-mixing and cleaning.
"What we needed to take into account was, on the one hand, that the aggregates transport sensitive active substances for further purification in the liquid chromatography process and, on the other hand, that the carriers heptane and ethyl acetate have solvent properties that need specific attention," Biolcati explained. "Therefore, gentle, stable metering had to be ensured even in the low capacity range." With a low NPSHr value, the Ecodos models offer good suction behavior here, so that cavitation does not occur even with carrier fluids with low viscosity, such as volatile solvents. In addition, the organic substances coming from the bioreactor are conveyed particularly gently, as the shearing effect in the metering process is very low. Downstream, the vaccine is obtained from them in the chromatography process step.
Wide adjustment range and high precision
"An additional requirement was the need for extremely accurate metering over a wide range of capacities," Biolcati said. "Particularly with the Ecodos pumps, the flow rate can be kept constant here with the help of the controllable motors via the speed with a maximum deviation of +/- 1 percent." In combination with the pressure-stiff characteristic curve, a precise and reproducible flow rate is guaranteed even with fluctuating back pressure. The fluids are metered precisely to the milliliter and, in addition, are conveyed in sufficient quantities for the comprehensive production of vaccines. If an adjustment to the composition of the vaccine becomes necessary at a later date or a larger volume of vaccine is 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 in order to exclude impurities or contamination of the fluids. Thanks to its compact design optimized for steam cleaning, the Ecodos variant also takes the difficult conditions in the GMP environment into account.
Pumps delivered in time for the start of production
Despite the special requirements for 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 the ambitious goal," Biolcati said in summary. "We are very proud to have made this small contribution to the global fight against the pandemic." As of January 2021, the new units are in successful operation without any failures.