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.