COVID-19 has put more pressure on vector suppliers, says expert

COVID-19 has increased demand for viral vectors, exacerbating concerns that supply constraints could slow the cell and gene therapy sector.

Gareth Macdonald

February 16, 2021

3 Min Read
COVID-19 has put more pressure on vector suppliers, says expert
Image: iStock/wildpixel

COVID-19 has increased demand for viral vectors, exacerbating concerns that supply constraints could slow the growth of the cell and gene therapy sector.

The ability to insert genetic material into cells using viral vectors is a cornerstone of the modern biopharmaceutical industry. Vectors are used to make everything from cell lines used to produce therapeutic proteins and monoclonal antibodies (mAbs) though to cell and gene therapies.


As a result, biopharma industry demand for vectors is strong. Indeed, a study published in 2019 suggested the surge in cell and gene therapy R&D resulted in demand exceeding supply. And despite various contract development and manufacturing organizations (CDMOs) investing in vector production capacity – with Discovery Labs and Forge Therapeutics being recent examples – there is likely still a mismatch according to co-author Joseph Rininger, director of cell and gene therapy at Latham Biopharma.


Image: iStock/wildpixel

“We are in the process of updating our model and forecast to accommodate these additions to clinical capacity, expanding the model to take into account commercial products and in-house capacity with recent, pending, and near-term approvals.  Preliminary analysis indicates that with the need for commercial capacity, the gap still exists and may have expanded,” he told BioProcess Insider.

Part of the issue is the difference in experience level amongst CDMOs between the two main vector types – adeno-associated viruses (AAV) for gene therapy and Lentivirus/Gamma Retrovirus for gene modified cell therapy or CAR-T Immunotherapy.

According to Rininger, “Innovator companies preferentially work with the CDMOs that have the most prior experience.  This may enhance the discrepancy between capacity and demand amongst developers leading to prolonged timeframes for commencing production activities.”


The coronavirus pandemic and the surge in related R&D is also impacting available vector production capacity.

“The vaccine response to the COVID-19 pandemic has further piled-on to the demand side especially for adenovirus vectors, with other vector-based approaches also trying to be tested. There are multiple viral vector vaccines being used to address the COIVD-19 pandemic.  This has dramatically increased demand.  Billions of vaccine doses are needed globally.

“Governments have entered into contractual relationships with developers and a subset of manufacturers to address this – in the United States, Emergent Biosolutions and Catalent are examples,” Rininger said.

Technical challenges

Another significant but sometimes overlooked constraint on vector production is the availability of plasmids. Most viral vectors are made using cell lines transiently transfected with plasmids.

Rininger told us “There are typically three plasmids required and they need to be cGMP manufactured and the demand for vector has led to a corresponding push for plasmid manufacture.  It can be a logistical challenge to align delivery of the plasmids with the manufacturing window to produce vector.

Similarly, the use of adherent mammalian HEK293 cell lines for vector production is also a constraint. The specialized cells need to be attached to a surface for successful culturing, which reduces the number that can be grown.

And, although new adherent culturing technologies like the iCellis reactor have been developed to try and address this problem, the challenges remains.

Other vectors can be produced using cells grown in suspension, but again there are constraints. Rininger told us “Suspension cells become hard to efficiently transduce with the plasmids as volumes increase thereby limiting most suspension cultures to 200L with mammalian cells.

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