Aseptic filling for cell therapies

Finding ther­a­pies for serious dis­eases – this has been the dri­ving force behind Mil­tenyi Biotec for over three decades. The com­pany also focuses on the dynam­i­cally growing field of cell and gene therapies.

Cologne, 1989: The physics stu­dent Stefan Mil­tenyi has an inge­nious idea. He coats small iron par­ti­cles with anti­bodies and cou­ples them to the recep­tors of cer­tain cells. By applying a mag­netic field, he suc­ceeds in iso­lating these cells from a sample, so “Mag­netic Acti­vated Cell Sorting” (or MACS for short) is born, which is used world­wide today in bio­phar­ma­ceu­tical and med­ical research.

With this tech­nology, Mil­tenyi lays the foun­da­tion for his own com­pany – Mil­tenyi Biotec – which he founds in Ber­gisch Glad­bach near Cologne in 1989. More than three decades later, he still runs the com­pany that bears his name. Since then, it has become a fron­trunner in biotechnology.

Hope for serious diseases

Around 4,700 employees work for Mil­tenyi Biotec world­wide, almost 25 % in R&D – so the pas­sion for new tech­nolo­gies still drives the com­pany, just as it did the young stu­dent back then. Mil­tenyi ­Biotec’s declared goal is to con­tribute with its tech­nolo­gies to the treat­ment of cancer, autoim­mune and neu­rode­gen­er­a­tive dis­eases. The com­pany is also involved in clin­ical studies relating to cell and gene ther­a­pies. These ther­a­pies are set to rev­o­lu­tionize med­i­cine, as they also offer huge poten­tial for serious dis­eases pre­vi­ously deemed incurable.

Cells in focus

Cell ther­a­pies with living cells are often used to replace the body’s dam­aged or defec­tive cells. In this process, cells are taken from a donor or the patient, pro­lif­er­ated out­side the body, and sub­se­quently re-admin­is­tered. Stem cell therapy is a prime example.

Gene ther­a­pies, how­ever, are designed to adapt genetic mate­rial – a faulty gene sequence can be replaced or repaired. DNA or RNA is intro­duced into body cells to achieve this. Prior to this ther­a­peutic admin­is­tra­tion, the engi­neered cells must also be cul­ti­vated out­side the body.

In both – cell and gene ther­a­pies – it is essen­tial to pro­lif­erate cells in a con­trolled way. Only then is there suf­fi­cient mate­rial for effec­tive therapy. This cell pro­lif­er­a­tion also fea­tures in one of Mil­tenyi Biotec’s cur­rent projects.

“As the cell prod­ucts are admin­is­tered to patients, aseptic pro­cessing is a top pri­ority.”Reiko Jen­ner­jahn,
Man­ager Liquid Solutions 
at Mil­tenyi Biotec

Sterile filling of bags

“This project is about filling cul­ti­va­tion medium for cells into bags. The medium is sub­se­quently used for growing the cells,” Reiko Jen­ner­jahn, Man­ager Liquid Solu­tions at Mil­tenyi Biotec, explains. “As the cells are admin­is­tered to patients, aseptic pro­cessing is a top pri­ority. While looking for avail­able auto­mated filling solu­tions, we came across Harro Höfliger, and its expe­ri­ence in aseptic bag filling raised our interest. We got in touch in May 2022 and together we con­ducted our first filling trials soon after.”

Tailor-made ther­a­pies,
tailor-made system

This resulted in a system that asep­ti­cally fills about 360 bags an hour. Depending on require­ments, up to three bag for­mats with dif­ferent vol­umes can be pro­duced. Sev­eral mea­sures ensure sterility throughout the process. Reiko Jen­ner­jahn says: “The pre-ster­il­ized bags are passed through a VHP air­lock to ensure sterility. In addi­tion, an iso­lator from our partner Franz Ziel GmbH is inte­grated to shield and con­trol the process envi­ron­ment. Mul­tiple bags are filled simul­ta­ne­ously, whereby a single-use system reduces the risk of con­t­a­m­i­na­tion.” The inte­grated weighing func­tion pro­vides for accu­rate results, which enables trend con­trol of the filling sta­tion. After filling, the bags are sealed, fol­lowed by 100 % ­Con­tainer Clo­sure Integrity Testing (CCIT) from WILCO.

The system fills about 360 bags an hour. Sev­eral mea­sures ensure sterility throughout the process. A note­worthy ele­ment is the inau­gural deploy­ment of Stäubli’s newly devel­oped Ster­i­clean+ robot.

With its indi­vid­u­ally coor­di­nated process steps, the system per­fectly exem­pli­fies ­baX­eptic. Harro Höfliger offers solu­tions under this brand name for aseptic bag appli­ca­tions. Reiko Jen­ner­jahn sums up: “Cell ther­a­pies are very promising, not least because they are indi­vid­u­al­ized to patients. A tailor-made system to facil­i­tate tailor-made treat­ments – it’s a per­fect match.”

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