Industrial Acceptance of Continuous Bioprocessing

In my previous blog, How Does Continuous Processing Align to Industry 4.0?, we examined how digitalization and artificial intelligence (AI) are key drivers for the commercialization of continuous processing of biopharmaceuticals through automation, control and data management supported with digital twins. I would like to now take the opportunity to reflect on the acceptance and adoption of continuous bioprocessing in our sector.

I have been fortunate to have had the opportunity to participate in four international conferences over the past three months where the emphasis has been very much on continuous processing:

• BioProcess International, Boston 9-12 September 2019
• The Asia Biopharma Continuous Manufacturing & Process Innovation Conference 2019, Shanghai 19-20 September 2019
• Integrated Continuous Biomanufacturing IV, Brewster 6-10 October 2019
• BioProduction 2019, Frankfurt 5-7 November 2019

It was reassuring to see full meeting rooms and large delegate numbers at each of these events and to listen to the number of continuous talks delivered at each conference. It is quite apparent that continuous processing is no longer something we speculate about, it is now a reality. During each of these conferences several case studies were given by leading biotechnology organizations on their progress to implementing continuous bioprocessing as they move out of process development (PD) and towards GMP production of clinical material.

Earlier in 2019, BiosanaPharma received approval to commence a Phase I clinical trial for a biosimilar version of omalizumab, the first monoclonal antibody produced with a fully continuous biomanufacturing process1. This was a pivotal moment in the acceptance of continuous manufacturing in the biopharmaceutical sector which really underpinned the themes being discussed during these recent conferences and paves the way to a new era in commercial bioprocessing.

In the past, we have spoken about fully integrated end-to-end continuous processes and while this may still be the ultimate goal, it may not always be the best place to start. A more prudent strategy could be to adopt a hybrid approach. Here we would typically start with a batch process and analyze which are the most critical process steps where improvements would offer significant productivity gains. These are the stages where the replacement of a batch unit operation to one operating in a continuous manner may yield significant process economic gains.

One area that is receiving attention is cell culture moving from fed batch to perfusion. This can be both during seeding to remove an N-x stage and/or replacing production bioreactors with perfusion systems. With recent increases in cellular productivity under perfusion conditions and culture media and perfusion rate optimization a continuous stream of cell-free harvest can now be produced for downstream processing. At each of these conferences various presentations were given where perfusion was the preferred approach for cell culture.

The capture chromatography steps and virus inactivation steps are additional areas that are being evaluated for continuous processing as part of a hybrid process. A number of approaches have been described for continuous or continual chromatography and these were covered by several speakers during the conferences. The use of multicolumn chromatography systems or parallel batch chromatography systems suitable for GMP operation enable continuous capture chromatography and provide a continual stream of eluate for subsequent processing. Whilst each approach may have benefits and drawbacks, the overall advantage using either approach is a reduction in the size of the capture chromatography columns being used which impacts not only costs of the chromatography sorbent but also the column sizes required. Additionally, the facility footprint both during use and potentially during storage should be smaller and there should be a favorable benefit on fluid management strategies.

Several technology approaches to carrying out the virus inactivation stage in a continuous or semi-continuous manner were described during these conferences and commercial solutions are now being employed during larger scale runs.

Automation and control, the ability to carry out on-line or at-line analytics, and data management continue to be the subject of much discussion, and with new technologies being introduced and reported upon this should not be regarded as a barrier to implementation of a continuous or hybrid process.

Given the technology advances we have seen, the move to GMP manufacture, and the number of data driven industrial presentations on continuous bioprocessing during 2019, the outlook for continuous bioprocessing in 2020 and beyond looks very promising indeed.

You can learn more about continuous bioprocessing here.

More to follow next time.   

References:

1. www.biosanapharma.com/news