HyPerforma DynaDrive Single-Use Bioreactor (S.U.B.)The new dynamic in cell culture performance

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The Thermo Scientifi c™ HyPerforma™ Single-Use Bioreactor (S.U.B.) is one of the most widely used S.U.B.s designed for mammalian cell culture. We fi rst launched the HyPerforma S.U.B. in 2006 and updated its design in 2013, while maintaining its robust, top-down, stirred-tank mixing system. The HyPerforma S.U.B. has been widely adopted in process development (PD) and clinical trials, as well as in bioproduction of cGMP cell culture. The new Thermo Scientifi c™ HyPerforma™ DynaDrive S.U.B. is the latest advancement based on our proven innovation, which o� ers better performance and accommodates larger volumes.

Key advantages• Large volume—50 L, 500 L, and option of scalability to

larger sizes of up to 5,000 L

• Improved seed train process—10:1 turndown ratio in the 50 L reactor and 20:1 turndown in the 500 L, plus projected larger-size reactors allow for streamlined seed-train process and help reduce risk

• Mixing times, power input per volume (PIV), and kLa performance are optimized for modern cell culture processes >100 million cells/mL

• Hardware optimized for perfusion cell culture processes

• Ergonomically friendly hardware—designed with the user in mind and allows for consistent and uniform BioProcess Container (BPC) loading

• Open-architecture approach—allows interoperability with available control systems

• The drive train is integrated in the HyPerforma DynaDrive BPCs, which are made with highly robust bioprocessing fi lm—the Thermo Scientifi c™ Aegis™5-14 fi lm

• The fi lm and components have been tested for leachable and extractable (L&E) evaluation according to BioPhorum Operations Group (BPOG) guidelines

Functional and scalableThe HyPerforma DynaDrive S.U.B. has evolved through our large-scale S.U.B. manufacturing experience of over 15 years. Our legacy HyPerforma 2:1 and 5:1 S.U.B.s will continue to serve their purpose; however, these single-impeller S.U.B.s have some limitations, such as scale, power, and turndown ratio. The new HyPerforma DynaDrive S.U.B. overcomes these limitations and enables optimal cell culture performance across all scales and increased cell densities. The hardware, drive train, and sparging approach have been redesigned to optimize mixing dynamics, scale, and performance.

Next-generation fl exible impeller drive train brings single-use technology to scalable bioreactors

Large volume—50 L, 500 L, and option of scalability to

Improved seed train process—10:1 turndown ratio in the 50 L reactor and 20:1 turndown in the 500 L, plus projected larger-size reactors allow for streamlined

Mixing times, power input per volume (PIV), and kLa performance are optimized for modern cell culture

Hardware optimized for perfusion cell culture processes

Ergonomically friendly hardware—designed with the user in mind and allows for consistent and uniform BioProcess

Open-architecture approach—allows interoperability with

The drive train is integrated in the HyPerforma DynaDrive BPCs, which are made with highly robust bioprocessing

The fi lm and components have been tested for leachable and extractable (L&E) evaluation according to BioPhorum

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Ergonomic and elegant tank designThe HyPerforma DynaDrive S.U.B. is the latest advancement in our line of elegantly designed and highly functional S.U.B. hardware. It is designed to meet 21 CFR 820 cGMP requirements. All sizes of the HyPerforma DynaDrive S.U.B. include doors that provide ample space for BPC loading. The doors have been carefully designed so all probe ports and tubing line sets are positioned correctly and easily without the need to be put through constrained holes. The S.U.B. tank provides a small footprint and o� ers easy cleaning capabilities associated with an open-cart frame.

• Simple BPC loading with vertical access door on all sizes

• The size of the hardware helps minimize precious lab space with minimized vessel footprint

• Reduce hold-up volumes with smartly designed tank fl oor

E� cient and fastThe water-jacketed design helps enable fast heat-up and cool-down times, reducing process cycle time. The water-jacketed system at the bottom of the S.U.B. increases surface area, improving heat transfer from low-volume cultures.

• Optimal-precision load cells and standard sight-volume indicators allow you to keep your processes running e� ciently

• Optional brushless DC motor includes encoder feedback for improved RPM accuracy and is ground-fault circuit interrupter (GFCI)–compatible

• 3/8 in. dimpled jacket improves fl ow rate through the water jacket for higher-performance temperature control

• Graduated sight-volume indicators accommodate visual volume references at a glance

Ease of use at the highest level

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advancement in our line of elegantly designed and highly functional S.U.B. hardware. It is designed to meet 21 CFR

DynaDrive S.U.B. include doors that provide ample space for BPC loading. The doors have been carefully designed

correctly and easily without the need to be put through

footprint and o� ers easy cleaning capabilities associated

Simple BPC loading with vertical access door on all sizes

The size of the hardware helps minimize precious lab

The water-jacketed system at the bottom of the S.U.B.

Optional brushless DC motor includes encoder feedback for improved RPM accuracy and is ground-fault circuit

3/8 in. dimpled jacket improves fl ow rate through the water jacket for higher-performance temperature control

Graduated sight-volume indicators accommodate visual

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Unsurpassed performance

Seed-train turndown ratioThe HyPerforma DynaDrive S.U.B. brings a new level of performance to single-use bioprocessing. A >10:1 seed-train turndown ratio allows users to optimize the seed train, which helps reduce labor and risk and improves facility space utilization. With a 10:1 (50 L S.U.B) and 20:1 (500 L S.U.B.) seed-train turndown ratio, users are able to transfer highly concentrated cells directly from cell culture fl asks to the S.U.B., thus treating the S.U.B. as an n-3, n-2, and n-1 reactor. The HyPerforma DynaDrive S.U.B. has been uniquely designed to allow for mixing and PAT (Process Analytical Technology) at low volumes.

Benefi ts of 10:1 turndown ratioWe will build what you need, while maintaining our quality and delivery times. Through our open-architecture approach, we have developed a variety of single-use sensors, tubing, and connectors to maximize your design fl exibility.

• Streamlining of bioprocesses by reducing seed-vessel requirements and maximizing process-vessel usage

• Seed vessels run at ≤10% volume, enabling n-1 and potentially n-2 or n-3 in a single vessel

• Reduces hardware and single-use bag requirements

• Reduces cell transfers and associated adaptation

• 10:1 turndown ratio enables running the 50 L bioreactor in as low as 5 L working volume; or with 20:1 turndown in the 500 L bioreactor, run as low as 25 L working volume for seed train

Power input per volume (PIV) and mixing times

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Improved PIV is critical to support the cell growth potential of modern cell lines and processes. PIV is normally enhanced by increasing either the RPM or the size of the impeller. Both of these changes can have detrimental e� ects, such as fl ooding of the impeller, or worse, cell shearing. Another way to increase PIV is to implement multiple impellers. For years, multiple impellers have been common in large stainless steel bioreactors. Some single-use bioreactors also have multiple impellers, but they are ridged and di� cult to maneuver, store, and deploy.

The HyPerforma DynaDrive S.U.B. has been designed specifi cally to increase PIV. The fl exible drive train includes multiple impellers that provide more PIV while still maintaining reasonable RPM and tip speeds. The unique drive train is also fl exible, which allows the BPC to be folded to minimize the size of packaging and improve BPC deployment and disassembly.

The increased number of impellers, location of the impellers, and cubical design of the reactor not only provide impressive PIV, but also improve mixing times of the bulk fl uid. Mixing times have been confi rmed to be less than 60 seconds at all scales, from 50 L to 5,000 L.

O2 and CO2 mass transfer (kLa)HyPerforma S.U.B.s utilize a drilled hole sparge (DHS) for optimal kLa performance. The DHS used in the HyPerforma DynaDrive S.U.B. has been enhanced and specifi cally designed to optimize the kLa performance. The laser-cut holes in the DHS are smaller and the quantity has been increased so that bubble size is uniform and sized properly for O2 delivery and CO2 stripping.

The cubical design and impeller placement also increase the residence time of the bubbles in the reactor. As bulk-fl uid mixing occurs, the bubbles are pulled into and down the drive train, which optimizes the time needed for mass transfer. Results have shown that mass transfer kLa is better in the HyPerforma DynaDrive S.U.B. than the standard HyPerforma S.U.B. with 0.1 vvm fl ow. Therefore, the HyPerforma DynaDrive S.U.B. allows users to increase their cell culture performance by utilizing the better kLa. Or, users can achieve the same kLa that they are used to but with a lower air-fl ow rate.

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Volume fl exibility within the reactorUsers often wish to multipurpose their reactor and run various processes within the same vessel. The HyPerforma DynaDrive S.U.B. provides that fl exibility. High-density cell culture can be achieved and maintained at 4:1 turndown ratios. That means that the same 50 L reactor can be used as a 12–50 L terminal volume reactor; or the 500 L HyPerforma DynaDrive S.U.B can be used as a 120–500 L reactor. Leveraging this fl exibility means more of the same type and size of vessels can be used in a fl exible volume manufacturing or PD suite.

Controller optionsThe Thermo Scientifi c™ HyPerforma™ G3Lite™ and G3Pro™

Controllers comprise an open-architecture system that can be integrated with the HyPerforma DynaDrive S.U.B. as well as any single-use bioreactor from other suppliers.

The system consists of a control tower that leverages intelligent transmitters, mass fl ow controllers (MFCs), pumps, sensors, and Thermo Scientifi c™ TruBio™ software that facilitates easy, reliable, and repeatable process development and commercial cell culture processes.

HyPerforma G3Lite and G3Pro Controllers are confi gurable, and the cGMP-compliant (21 CFR 820) TruBio software is powered by DeltaV™ control systems from Emerson. These are fully self-contained, movable units that can be operated as a stand-alone system (for one vessel) or networked for multiple vessels. They are engineered to optimize capital cost for use in non-GMP or cGMP-certifi ed production facilities.

Features• Stand-alone or networked (for multiple vessels)—enabled

by distributed control system (DCS)

• Includes up to six MFCs with air, O2, N2, CO2 for drilled-hole spargers (DHSs); air for frit or open-pipe spargers; air for overlays

• Probe confi guration options—fl exibility to connect electrochemical, single-use, or both for pH and dissolved oxygen (DO) measurements

• Foam level, load cell, and Thermo Scientifi c™ TruTorr™ II pressure transmitters are included in the controller

• Scalability—transfer any process from 50 L up to 5,000 L

• Modularity—predefi ned confi gurations available for 50 L to 5,000 L bioreactors

• Scales and pumps available for multifeed purpose, including four peristaltic pumps for acid, alkali, antifoam, and feed

• Includes vent fi lter heater controller

• Touchscreen interface for easy data entry and control when necessary

• Temperature control unit (TCU) integration options available for implementing a temperature control strategy

Benefi ts• Open-architecture capabilities to integrate and

communicate with vessels from other suppliers* (Sartorius, Millipore, and GE)

• Return on investment (ROI)—increase productivity and minimize downtime

• Scalability and streamlined datafl ow enabled by TruBio software powered by the DeltaV automation platform

For specifi cations and more information on the HyPerforma G3Lite and G3Pro controllers, refer to the appropriate product data sheet or contact your sales representative.

* Depending on the vessel type and model, an engineered-to-order (ETO) product may be needed.

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BioProcess Containers

Quality and performanceThe BPCs for the HyPerforma DynaDrive S.U.B. are available with our proprietary Aegis5-14 fi lm. Our fi lm is widely used today by a large number of global biopharmaceutical companies for all bioprocessing steps. Aegis5-14 fi lm was introduced in 2013 and has a clean profi le tested to BPOG standards.

We have completed the BPOG L&E testing guidelines for all components used in HyPerforma DynaDrive BPCs.

Key benefi tsWe can address your specifi c application with either a standard or customized confi guration. The standard designs are confi gured for a variety of applications, while the custom designs are for customer-specifi c applications. The key benefi ts for our BPCs include:

• The latest sensor technology in single-use or autoclavable probes, including:

– pH—electrochemical single-use or reusable probes, and optical single-use sensor

– pO2—optical single-use or reusable probes

– Foam—single-use foam sensor built into BPC

– Capacitance—single-use sensor or reusable probe

– Raman—optical probe port into BPC

– And many more

• Optional ports for ATF (alternating tangential fl ow) or TFF (tangential fl ow fi ltration)

• Built-in condenser system for 3,000 L and 5,000 L BPCs, which helps extend the life and reduce the quantity of exhaust fi lters needed

• Utilization of crossfl ow sparging technology to assure proper head-space gas mixing during low-volume seed or terminal cell cultures

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S.U.B. hardware dimensions and weights

Width with standard E-Box Depth Height with fi lter

brackets Jacketed tank, dry weight

Jacketed tank, wet weight (at full working volume)Dimensions (W x L x H)

50 L 40.5 in. (102.8 cm)

24.4 in. (62.0 cm)

91.2 in. (231.5 cm)

290 lbs (131.5 kg)

400 lbs (181.5 kg)

500 L 47.2 in. (120.0 cm)

38.5 in. (97.7 cm)

118.4 in. (300.6 cm)

985 lbs (446.7 kg)

2,087 lbs (946.7 kg)

3,000 L 72.2 in. (183.5 cm)

56.8 in. (144.3 cm)

135.7 in. (334.6 cm)

4,464 lb (2,025 kg)

11,189 lb (5,075 kg)

5,000 L 72.2 in. (183.5 cm)

56.8 in. (144.3 cm)

191.2 in. (485.6 cm)

5,973 lb (2,710 kg)

17,108 lb (7,760 kg)

Specifi cations

50 L 500 L 3,000 L 5,000 L

Liquid working volume 50 L 500 L 3,000 L 5,000 L

Total reactor volume 65 L 580 L 3,700 L 5,700 L

Fluid geometry at working volume (height:equivalent diameter)

2.5:1 2.5:1 1.5:1 2.5:1

Impeller (quantity x blade count) 4 x 2 4 x 2 3 x 2 5 x 2

Mixing rate range 30–250 RPM 30–160 RPM To be released

BPC install assist Yes—manual BPC mechanical assist

Yes—automated motor and fi lter lift assist

Yes, complete motor, fi lter, condenser, and utilities lift mechanism

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Knowledgeable and comprehensive technical support

Our global, fi eld-based technical support team is available for local installation and support. A process development team is available for cell culture support, providing expertise on cell growth and troubleshooting. We can also provide you with additional support documentation upon request.

All systems are supplied with:

• Comprehensive user guide

• Equipment turnover package (ETP)

• Validation guide

PERFORMANCE

COLLABORATIO

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BIOPROCESSING BY DESIGN

Open architectureRecord of success

Adaptive innovation

Holistic approach

Tailored solutionsAssurance of supply

Quality and safety

Productivity

To meet the increasing demand for biologics worldwide, you need to expect more from suppliers. It isn’t just about the products we deliver, but how we do business together.

With a collaborative approach that is grounded in our technical knowledge, we work with you to achieve optimal bioprocessing outcomes. Committed to identifying the technologies and services that address your needs, from drug development through large-scale commercial production, we provide integrated and tailored solutions that improve the overall biomanufacturing experience. If a solution doesn’t exist, we’ll build it—together.

Bioprocessing by Design Driving performance through collaboration

And while we are fl exible in our approach, we are uncompromising in our pursuit of performance. Through technical engagement, innovative product design, and strategic sourcing programs, we deliver productivity, quality, and assurance of supply so that you can have complete confi dence in the e� ciency and speed of your biologics development and manufacturing processes.

That’s our commitment to you, and it’s what we call Bioprocessing by Design.

For Research Use or Further Manufacturing. Not for diagnostic use or direct administration into humans or animals. © 2019 Thermo Fisher Scientifi c Inc. All rights reserved. All trademarks are the property of Thermo Fisher Scientifi c and its subsidiaries unless otherwise specifi ed. DeltaV is a trademark of Emerson Corp. COL33220 1019

Find out more at thermofi sher.com/dynadrive