Frequently Asked Questions
1. Which applications work best with your technology?
PBS Biotech's Vertical-Wheel™ (VW) Single-Use Bioreactor System has been designed for cell therapy (stem cells) and therapeutic protein (mammalian and insect cells) processes in batch, fed-batch, and perfusion modes.
2. What are the primary components of the Vertical-Wheel™ Bioreactor?
The VW Bioreactor System consists of two main components: a single-use vessel/bag where cells are grown and the product is produced, and the non-disposable unit with an integrated controller that houses the single-use vessel/bag. The single-use disposable vessels and bags are available in sizes from 0.1 L to 500 L working volumes. They are sterilized by gamma radiation and shipped ready-to-use. Each vessel/bag includes all components that are necessary for promoting cell growth, and all product-contact surfaces are made out of USP Class VI certified materials.
3. Do all of the Vertical-Wheel™ Bioreactors use bags?
Most VW Bioreactors use single-use bags made of polyvinylidene fluoride (PVDF). The PBS 3 and PBS MINI use hard plastic vessels that are made of polycarbonate.
4. What does the Vertical-Wheel™ Bioreactor use for agitation?
All VW Bioreactor vessels/bags contain a novel, vertically-oriented impeller with internal bi-directional vanes that rotates around a fixed shaft to create a gentle, three-dimensional liquid flow pattern. In AirDrive™ systems, the VW impeller rotation is powered by the buoyant force of the sparger gas, while in MagDrive™ systems, the VW impeller rotation is powered by magnetic coupling with the bioreactor housing.
5. What is the maximum cell density for VW Bioreactors?
Our system has proven capable of supporting viable cell densities exceeding 30×10⁶ cells/mL. Other tests have shown comparable cell growth performance and productivity between the VW Bioreactors and other systems currently on the market, which include both traditional stainless-steel tanks and other single-use systems. Testing has shown that our systems can achieve oxygen mass transfer rate (kLa) of up to 20 hr⁻¹ using our microsparger elements.
6. How scalable is the VW Bioreactor?
Thanks to the unique design of the VW impeller, the mixing characteristics of the VW Bioreactors are very homogeneous across all scales. This includes mixing time, average shear rate, and turbulent energy dissipation rates. This homogeneity greatly facilitates process scale-up from small development volumes to full production volumes.
7. What is involved in cleaning the system?
Absolutely no cleaning is required, as each single-use vessel/bag is delivered clean and sterilized by gamma radiation prior to shipment to the customer. The stainless-steel housing is never in contact with process fluids and can be wiped down just like any piece of laboratory equipment.
8. What is involved in the validation of the Vertical-Wheel™ Bioreactor System?
PBS Biotech can work with you to validate our systems in your facility. We will provide you with a comprehensive validation-ready package to assist you in your validation effort.
9. Can it be used for vaccine production?
The VW Bioreactor System is a completely closed system and can handle high containment requirement applications as well as cGMP operations. The low shear environment in the VW Bioreactor can potentially expedite and improve virus and vaccine production.
10. Will you provide results from you Leachables and Extractables Testing?
Leachables and Extractables testing will be performed on our bioreactor system in accordance with guidelines set forth by Bio-Process Systems Alliance (BPSA) and BioPhorum Operations Group (BPOG). Our test approach will be reviewed by consultants specializing in single-use bag validation, and the testing will be performed by a contract laboratory specializing in leachables and extractables testing.
11. I already have a Distributed Control System (DCS) in my facility. Can I use it to control the Vertical-Wheel™ Bioreactor?
The VW Bioreactor System has full OPC connectivity, and the controller can be configured to pass full control to the DCS.
12. Is the Vertical-Wheel™ Bioreactor qualified for cGMP applications?
The VW Bioreactors are designed for use in cGMP applications for manufacture of human therapeutics. All materials used in our vessel/bag that could potentially contact the drug substance conform to USP Class VI and ISO 10993 standards.
13. How easy is a Vertical-Wheel™ Bioreactor to operate?
Our bioreactors have been designed for plug & play simplicity with our integrated software, so they are very easy to use. As the VW Bioreactors come completely pre-configured, one only needs to plug it into an electrical outlet, connect gas supplies, and turn it on. Some of our customers have taken delivery of VW Bioreactors in the morning and inoculated them by the same afternoon.
14. What kind of special gas, utilities, or services are needed?
The VW Bioreactor System only requires electricity and compressed gasses. The bioreactors are designed to run with four gases - air, nitrogen, oxygen and carbon dioxide - but they can also run without nitrogen. The bioreactors are designed to connect to your Ethernet network for remote monitoring and control over the World Wide Web.
15. What kind of testing has been done on the device?
We have performed biological testing in the VW Bioreactor in parallel with other bioreactor systems to compare the culture growth, productivity, and product quality. In addition, fluid dynamics studies have been performed at various scales to quantify mixing time and volumetric mass transfer rate (kLa). The fluid mixing pattern, shear stress levels, and turbulent kinetic energy dissipation rates have also been investigated using computational fluid dynamics (CFD) modeling on both ANSYS Fluent and STAR-CCM+® software.
16. Is the VW impeller an essential part of the single-use vessel/bag construction?
Yes, the disposable VW-Wheel impeller is integral to our bag design as it drives the motion of the fluid inside the vessel/bag. The vertically-oriented wheel rotates freely about a shaft that is anchored to the vessel/bag. All parts that come in contact with the product are made out of USP Class VI materials and disposable.
17. How does the gas flow control work in Vertical-Wheel™ Bioreactor systems?
A gas mixture, comprised of varying composition of air, carbon dioxide, and nitrogen (if applicable), is either sparged into the system through an orifice at the bottom of the vessel/bag (in AirDrive systems) or in the headspace of the vessel/bag as overlay (in MagDrive systems). The exact composition will be dictated either by the user or by the automatic pH and dissolved oxygen (DO) controls. Pure oxygen is supplemented into the vessel/bag as needed to maintain high viable cell densities during the late stage of a production cell culture process.
18. Does the Vertical-Wheel ™ Bioreactor System accommodate pH and DO sensors? Will they be reusable or single-use?
All VW systems larger than PBS MINI will come equipped with pH and DO control capabilities, with redundancies in measurements for PBS 80 and PBS 500. There is an option to use reusable sensors or single-use sensors depending on customer's request. PBS MINI will not have active pH and DO control on the system, so it must rely on controls provided by the carbon dioxide incubator in which it will be housed.
19. How is the temperature of the culture controlled?
The temperature of the culture is measured non-invasively by resistive temperature detectors (RTD) on the non-disposable housing unit. Once the vessel/bag has been installed, the RTD on the housing comes in direct contact with the back portion of the vessel/bag and is sufficiently insulated from the conductive metal housing to ensure that it accurately measures the temperature of the vessel/bag. The temperature of the culture can be maintained at a set point using the automatic mode of our temperature control. Heat is applied to the vessel/bag as needed using heating pads placed along the bottom curvature of the housing.
20. What are the major benefits of the Vertical-Wheel™ Bioreactor over existing technology?
The major advantage of the VW Bioreactor over existing systems is the broad scalability that it can offer, from the R&D and bench-top scale to cGMP production scale. Since all of our bioreactors use the same mixing mechanism, a bench-top unit can be used as a representative scale-down model during early-stage process development, as well as process characterization for the large scale bioreactors. In addition, the power input (from the buoyancy of gas) dissipated over a larger mixing device creates more uniform and gentle fluid motion, which provides a lower shear environment even at large scale (estimated by CFD analysis using ANSYS Fluent and STAR-CCM+® software). This technology has the potential to accelerate time to market by virtually eliminating the potential technology transfer challenges that are often encountered as a process moves from R&D phase to clinical and commercial phases. Finally, the VW-Wheel bioreactors have the smallest comparative footprint and are the easy to install and use.
For product evaluation requests, application and engineering questions, and customer support, please contact us at info@pbsbiotech.com or call us at +1 (805) 482-7272.