PBS Applications

Cell Therapies Application

Stem cell therapy has rapidly grown in interest in recent years, as advanced treatments based on stem cells give the potential to cure a wide variety of serious diseases and infirmities. However, in many applications, large volumes of stem cells are required.

One of the scalable approaches for large volume production of stem cells is to grow them on microcarriers (MCs) suspended in a bioreactor as a 3D culture to utilize its entire volume and provide more uniform culturing conditions for the cells to maintain cell homogeneity.  The Vertical-Wheel™ Bioreactor System offers an advantage to other bioreactor systems in its ability to keep the MC’s in suspension during culture at low agitation rate due to the vertically-oriented wheel, while imparting low shear stress to the cells with gentle mixing thanks to the large surface area of the impeller that allows cells to attach quickly and evenly on the MCs.

Bone-Marrow Derived Human Mesenchymal Stem Cells (BM-hMSCs), a commonly-used stem cell type for research and clinical trials, have been successfully cultured in the PBS 3 Vertical-Wheel™ Bioreactor System to very high cell densities.

Scalability of the Vertical-Wheel™ design has also been demonstrated using hMSCs and serum free cell culture medium, resulting in consistently high growth rate (1.7-1.8 day doubling time) in PBS 0.5 and PBS 3 systems.  

The PBS 0.1 and PBS 0.5 MINI Bioreactor systems are ideal for early-stage process development, as they require smaller quantities of expensive reagents to perform screening studies.

PBS Biotech is continually working to generate cutting-edge results in the Vertical-Wheel™ Bioreactor System for Cell Therapy application, including process scale-up to larger working volumes such as the PBS 15 and PBS 80 systems, as well as development of low volume in-situ harvesting methodologies.  Other cells such as T-cells, induced pluripotent stem cells (iPSC) and human embryonic stem cells (hES) have also been studied in the Vertical-Wheel™ Bioreactor System.

For this particular application, PBS Biotech generally recommends the MagDrive option of the Vertical-Wheel™ Bioreactor System.

Therapeutic Proteins Application

In this field, processes are typically optimized to culture cells to very high densities involving complex media and multiple nutrient feeds at small scale and then scaled up to larger working volumes.  Oftentimes, inconsistencies in cell culture performance arise during process scale-up due to differences in the impeller and vessel geometries of the bioreactors, which can result in different shear stress and foam profiles.  The Vertical-Wheel™ Bioreactor System from PBS Biotech can help alleviate this scale-up issue by offering a consistent Vertical-Wheel™ impeller and vessel shape design from 0.1 L to 500 L scales.

A fed-batch process involving a hybridoma cell line expressing a monoclonal antibody (mAb) has been successfully scaled up from 3 L to 500 L scale in the Vertical-Wheel™ Bioreactor System, where agitation rates in the larger bioreactors were set by maintaining the same impeller power input per volume (P/V) as the 3 L.  Comparable viable cell densities and protein titers were achieved across all bioreactor sizes (PBS 3, PBS 15, PBS 80, and PBS 500).

A high density fed-batch process using lactate-adapted CHO DG44 cells has also successfully been cultured in 3L and 15L Vertical-Wheel™ Bioreactor Systems, showing comparable peak viable cell density of 25 million cell/mL and >90% viability was maintained through 12 days of culture.

PBS Biotech is continually working to generate cutting-edge results in the Vertical-Wheel™ Bioreactor System for Therapeutic Protein application, including more challenging processes that involve continuous medium exchange with perfusion devices to push cell densities even further.

For this particular application, PBS Biotech generally recommends the AirDrive option of the Vertical-Wheel™ Bioreactor System.

Vaccines and Virus Production Application

The following cell lines have been tested in the PBS AirDrive Vertical-Wheel™ Bioreactors in pursuit of vaccine or virus production applications:

Anchorage-dependent cell lines on microcarriers:
– MDCK (for a bird-flu vaccine)
– MRC-5
– A549

Suspension-adapted cell lines for vaccine or virus production:
– SF9
– PER.C6®
– 293S
– MDCK (suspension-adapted cells for human influenza vaccine)

Using the cell lines listed above, the following vaccines and viruses have been produced in PBS AirDrive bioreactors with results equivalent to or better than conventional stirred bioreactor technology:
– Herpes Zoster Virus (PBS 3)
– Oncolytic Adenovirus (PBS 3)
– Human Influenza Virus (PBS 3, PBS 15, and PBS 80)

For this particular application, either the MagDrive or AirDrive option of the Vertical-Wheel™ Bioreactor System is applicable.