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Protection of Biomanufacturing Processes from Virus Contamination through Upstream Virus Filtration of Cell Culture Media
  • Andreas Wieser,
  • Jens Modrof,
  • Thomas Kreil
Andreas Wieser
Takeda Manufacturing Austria AG
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Jens Modrof
Takeda Manufacturing Austria AG
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Thomas Kreil
Takeda Manufacturing Austria AG

Corresponding Author:[email protected]

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Medical progress as enabled by early plasma products has also revealed biological safety challenges. The combination of donor selection, donation testing and virus reduction processes has effectively addressed these concerns, and today medicinal plasma products feature significant safety margins. The safety tripod concept has since been adapted to biotechnology manufacturing platforms and has also ensured the safety of these products. However, cell-based manufacturing processes have occasionally been exposed to adventitious viruses, leading to manufacturing interruptions and unstable supply situations. The rapid progress of advanced therapy medicinal products (ATMPs) needs an innovative approach to ensure the learnings from more traditional biotechnology help to avoid any unwelcome reminder of the universal presence of viruses. The introduction of up-stream virus clearance steps has already been shown to be valuable for any products too complex for down-stream interventions in the sense of both assuring product safety and continuous supply. The gentlest method being virus filtration – the development of which is presented here. The experiments investigated the feasibility of implementing culture media virus filtration with respect to their virus clearance capacities under extreme conditions such as very high process feed loading (up to ~ 19,000 L/m 2), very long duration (up to 31 days), and multiple process interruptions (up to 21, with cumulative interruptions of over 92 hours). Minute virus of mice (MMV) was used as a relevant target virus, and in general, as a model small non-enveloped virus, as these viruses are the main challenge for the investigated virus filters with a stipulated pore-size of about 20 nm. It was found that certain filters – especially of the newer 2 nd generation – are capable of effective virus clearance despite the harsh regimen they were subjected to. At the same time the investigation of biochemical parameters for un-spiked control runs showed the filters to have no measurable impact on the composition of the culture media. Based on these findings, this technology seems to be quite feasible for large volume pre-manufacturing process culture media preparations.
03 Apr 2023Submitted to Biotechnology and Bioengineering
04 Apr 2023Submission Checks Completed
04 Apr 2023Assigned to Editor
04 Apr 2023Review(s) Completed, Editorial Evaluation Pending
12 Apr 2023Reviewer(s) Assigned
03 May 2023Editorial Decision: Revise Major
23 May 20231st Revision Received
23 May 2023Submission Checks Completed
23 May 2023Assigned to Editor
23 May 2023Review(s) Completed, Editorial Evaluation Pending
29 May 2023Reviewer(s) Assigned
07 Jun 2023Editorial Decision: Accept