FAQs – Fast Facts about PBS Biotech’s Single-Use Bioreactor Systems
1. What applications are best for the PBS Bioreactor?
The PBS Single-Use Biroeactors System has been designed for mammalian and insect cell culture processes in batch, fed-batch, and perfusion modes.
2. What are the primary components of the PBS Bioreactor?
The PBS Single-Use Bioreactor System consists of two main components: 1) a single-use vessel where cells are grown and the product is produced, and 2) the non-disposable unit with an integrated controller that houses the single-use bag.
The single-use disposable vessels and bags are available in sizes from 3 to 500L working volumes (2500L Coming Soon). They are are pre-sterilized by gamma irradiation and shipped ready-to use. Each 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 the PBS reactors use bags?
Most PBS reactors use single-use bags made of PVDF. The PBS3 is the only exception: its vessel is a rigid box made of clear polycarbonate.
4. What does the PBS Bioreactor use for agitation?
The PBS Bioreactor vessels contain the Air-Wheel ™, a novel mixing mechanism powered only by the buoyant force of the sparge gas. It rotates around a fixed shaft to create a complex, three-dimensional fluid flow pattern inside the bag or box. The Air-Wheel ™ eliminates the need for a motor, mechanical seal, magnetic coupling, on any other kind of external mixing device.
5. What is the maximum cell density for PBS Bioreactor?
Our system has proven capability of supporting viable cell density exceeding 25×106 cells/mL. Other tests have shown comparable cell growth performance and productivity between the PBS Bioreactor 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 micro-sparger elements.
6. How scalable is the PBS Bioreactor?
The PBS Bioreactor System is available in 3L, 15L, 80L, and 500L maximum working volume with a 2500L unit coming soon. Thanks to the unique design of the Air-Wheel™ impeller, the mixing characteristics of the PBS reactors are very homogenous across all scales. This includes mixing time, average shear rate, and turbulent energy dissipation rates. This homogeneity greatly facilitates process scale-up from development scales to full production scale.
7. What is involved in cleaning the system?
Absolutely no cleaning is required, as each single-use vessel is delivered clean and pre-sterilized by gamma irradiation prior to shipment to the customer. The stainless-steel housing is not it contact with process fluids and can be wiped down just like any piece of laboratory equipment.
8. What is involved in validation of the PBS 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?
Absolutely. The PBS 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 PBS Bioreactor would potentially facilitate virus and vaccine production.
10. Will you provide results from your Leachables and Extractables Testing?
Yes, the leachables and extractables testing will be performed on our bioreactor system in accordance with guidelines set forth by Bio-Process Systems Alliance (BPSA) and other single-use systems manufacturers. 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 DCS in my facility. Can I use it to control the PBS Bioreactor?
Yes. The PBS Bioreactor System has full OPC connectivity, and the controller can be configured to pass full control to the DCS.
12. Is the PBS Bioreactor qualified for cGMP applications?
The PBS Bioreactor is designed for use in cGMP applications for manufacture of human therapeutics. All materials used in our bag that could potentially contact the drug substance conform to USP Class VI and ISO 10993 standards.
13. How easy is a PBS Bioreactors to operate?
Our Bioreactors have been designed for plug & play simplicity with our integrated software, so it is very easy to use. As the PBS bioreactor comes completely pre-configured, you only need to plug it into an electrical outlet, connect it to gas supplies, connect it to your network, and turn it on. Our customers have taken delivery of PBS reactors in the morning and had inoculated the reactors on the same afternoon.
14. What kind of special gas, utilities, or services are needed?
The PBS Bioreactor only requires electricity and compressed gasses. The reactors are designed to run with 4 gasses, Air, Nitrogen, Oxygen and Carbon Dioxide, but they can also run without Nitrogen. The reactors 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 PBS 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 Fluent™ software. The CFD models are currently being validated by Particle Image Velocimetry.
16. Is the Air Wheel™ an integral part of the single-use bag construction?
Yes, the Air-Wheel™ is integral to our bag design and disposable as it drives the motion of the fluid inside the bag. The wheel rotates freely about a shaft that is anchored to the bag and is powered by the buoyant force of the gas bubbles that are introduced from the bottom of the 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 PBS Bioreactor system?
A gas mixture, comprised of varying composition of air and carbon dioxide (and nitrogen if applicable), is sparged into the bag through an orifice at the bottom of the bag. The exact composition will be dictated by the pH and dissolved oxygen (DO) controls. Pure oxygen is supplemented into the bag as needed through a microsparger element to maintain high viable cell densities during the late stage of a production cell culture process.
18. Are there plans to incorporate DO and pH sensors? Will they be reusable or disposable sensors?
Each single-use bag (for 80L scale and larger) will come equipped with one set of disposable pH and DO sensors, as well as slots in the bag for aseptically inserting a set of reusable pH and DO sensors. At the 3L and 15L scales a set of reusable pH and DO sensors will be the standard, but a set of disposable pH and DO sensors will also be offered as an option per customer request.
19. How is 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 bag has been installed, the RTD on the housing comes in direct contact with the back portion of the bag and is sufficiently insulated from the conductive metal housing to ensure that it accurately measures the temperature of the bag. As with the pH and DO sensors, there is a redundant RTD to back up the controlling RTD in case of sensor failure.
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 bag as needed using heating pads placed along the bottom curvature of the housing.
20. What is the largest prototype built and tested to date?
In order to validate PBS Biotechs’ pneumatic mixing technology at large scale, a prototype with a maximum working volume of 5,000L has been built . Biological tests using a mammalian cell lines have been performed at 3L, 15L, 80L, and 250L scales, and the results showed that the PBS system can achieve comparable or superior cell culture performance (viable cell density, viability, product titer, and product quality) to that of conventional stainless-steel systems or existing single-use systems.
21. What does PBS view as their major benefits over existing technology?
The major advantage of the PBS Bioreactor over existing systems is the broad scalability that it can offer, from R&D/Bench-Top scale to cGMP production scale up to 5,000L working volume. The Bench-Top unit can be used as a representative scale-down model with the same mixing mechanism 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 Fluent™ 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 PBS reactors have the smallest footprint, and are the easiest to install and use.
