The PBS Bioreactor System has been designed for cell culture processes in batch, fed-batch, and perfusion modes.

The PBS Bioreactor System consists of two main components: 1) a single-use bag where cells are grown and the product is manufactured, and 2) the non-disposable unit with an integrated controller that houses the single-use bag.

The single-use bags, which are pre-sterilized by gamma irradiation and shipped ready-to-use to customers, will be available in sizes ranging from 2L to 5,000L working volumes. Each bag includes all components that are necessary for promoting cell growth, and all product-contact surfaces are made out of USP Class VI materials. The primary component of the single-use bag is the Air-Wheel™ and a novel mixing mechanism which obviates any the need for a mechanically-driven, external mixing device.

The PBS Bioreactor bag contains a novel mixing mechanism called the Air-Wheel™ which is powered simply by the buoyant force of the gas bubbles and rotates around a fixed shaft to create a complex, three-dimensional fluid flow pattern inside the bag. The efficiency of fluid mixing can be varied by altering the flow rate of the inlet gas through the main sparger.

Our system has proven capability of supporting viable cell density exceeding 10 x 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 10L system can achieve an oxygen mass transfer rate (k_La) of up to 19 hr^-1 using our microsparger element.

The PBS Bioreactor System will be available in sizes ranging from 2L to 3,500L with approximately a five-folds increase in working volume from unit to unit. Each unit can be operated within the range of minimum working volume (100%) and maximum working volume (150%). Therefore, the entire range of possible working volumes that PBS Bioreactor System can offer would be from 2L to 5,000L.

Absolutely no cleaning is required, as each single-use bag is pre-sterilized by gamma irradiation prior to shipment to the customer. The stainless-steel housing can be wiped down periodically using an applicable cleaning agent, per standard operating procedure for each facility.

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.

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 facilitates virus and vaccine production.

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.

Yes. The PBS Bioreactor System has full OPC connectivity, and the controller can be configured to pass full control to the DCS.

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.

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.

The PBS Bioreactor only requires electricity and gas sources. The system will require higher electrical power for large scale units (> 250L) for heating. However, the controller runs at standard electrical voltage, using 1.5 amp of current.

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 (k_La). The fluid mixing pattern, shear stress levels, and turbulent kinetic energy dissipation rates of the 10L and 1,000L pneumatic mixing systems have also been investigated using computational fluid dynamics (CFD) modeling on Fluent™ software.

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.

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.

Each single-use bag (for 50L 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 2L and 10L 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.

The temperature of the culture is measured non-invasively by a resistive temperature detector (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.

In order to validate the PBS Biotech's pneumatic mixing technology at large scale, the 3,500L system with 5,000L maximum working volume is the largest prototype built to date by PBS Biotech. Biological tests using a mammalian cell line have been performed at 2L, 10L, 50L, 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.

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.