mAb Process Scale-Up

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Support excellence in clinical and commercial manufacturing

Scaling monoclonal antibody (mAb) production introduces operational and regulatory pressures as processes move from development to clinical and commercial volumes. Teams must refine upstream (USP) and downstream (DSP) processes, manage increasing material demand, and maintain cGMP requirements. As working volumes expand, batch consistency, facility footprint, and supply reliability matter more. Thermo Fisher Scientific offers comprehensive solutions that support mAb scale-up while aligning with regulatory and sustainability goals.

Insights to scale mAb processes


Access a streamlined overview of the key steps and considerations in scaling mAb production from development to clinical and commercial scales.
 

Streamline upstream process scale-up

Support upstream performance as mAb production moves to larger volumes, where maintaining yield, managing resources, and sustaining consistent culture conditions can become more complex. Upstream development and intensification strategies, such as optimized media and feeds, targeted supplements, and scalable bioreactors, can help improve efficiency and support dependable scale-up.

Optimize media and feed solutions with Gibco

Support cell growth needs and maintain consistent upstream performance across increasing volumes with Gibco Chinese hamster ovary (CHO) cell media, feeds, and supplements.

 

Simplify process scale-up with the DynaDrive S.U.B.

Use the Thermo Scientific DynaDrive Single-Use Bioreactor (S.U.B.), available in sizes from 5 L to 5,000 L, to support efficient mixing and streamline movement from development to larger manufacturing scales.
 

Simplify harvest with the DynaSpin Single-Use Centrifuge

Apply the Thermo Scientific DynaSpin Single-Use Centrifuge to support efficient cell harvest with reduced buffer and filter use. It is compatible with 3M™ Harvest RC Centrate Chromatographic Clarifier and 3M™ LifeASSURE PDA filters.

Enable downstream process scale-up

The mAb downstream workflow includes affinity chromatography, viral inactivation, and polishing to help purify antibodies, reduce viral risks, and minimize impurities. Using scalable formats and process-appropriate resins supports reliable purification outcomes as batch volumes increase.

Scale capture and polish with chromatography optimization

Support purification performance by applying affinity chromatography to selectively bind and recover the target antibody, supporting efficient reduction of early-stage impurities. Facilitate polish operations in downstream processing using anion exchange chromatography (AEX), cation exchange chromatography (CEX), or hydrophobic interaction chromatography (HIC) resins to reduce host cell proteins (HCPs), residual DNA, aggregates, and other contaminants, thereby improving product purity and quality. Tools, such as the Bioprocess Resin Selection Tool and the downstream buffer calculator, can help guide resin and buffer selection for your application.

Connected solutions for downstream scale-up

Downstream process development benefits from coordinated capture, polish, and buffer management strategies. Integrating chromatography platforms, resin selection, and process liquid solutions helps align purification capacity with increasing production demands.

MabCaptureC Protein A resin

MabCaptureC Protein A resin is developed for efficient capture with a high-capacity, cross-linked agarose matrix suited for production process-scale purification of mAbs.
 

DynaChrom Single-Use Chromatography System

Support a wide range of flow rates and process volumes during scale-up with Thermo Scientific DynaChrom Single-Use Chromatography System. In-line dilution capability helps reduce process liquid use and footprint requirements.

POROS polish resins

Apply POROS AEX, CEX, HIC resins, as well as mixed-mode resin, to help address impurities during polish steps. These resins support the reduction of aggregates, charge variants, HCPs, and residual DNA as workflows scale.

Gibco process liquids

Simplify weigh-dispense-hydrate workflows with ready-to-hydrate dry powders and ready-to-use liquids. Concentrates and in-line dilution help reduce preparation footprint and support efficient buffer manufacturing.

Reduce risk with viral inactivation and impurity testing

Support downstream reliability through controlled viral inactivation and analytical tools that quantify impurities, such as residual DNA, proteins, and microbial contaminants. These methods support process consistency as production scales.

Enable viral inactivation


Achieve consistent mixing for low-pH viral inactivation with Thermo Scientific imPULSE Mixer, featuring disc-based mixing, configurable controls, and sizes from 30 L to 5,000 L.


 

Maintain quality and process insights

Apply PCR-based impurity testing, including Applied Biosystems resDNASEQ Residual Host Cell DNA Quantitation Kits and Applied Biosystems ViralSEQ Vesivirus Detection Kits, designed to monitor residual DNA, proteins, and potential contaminants.

Reduce bioburden between downstream operational steps

Use 3M™ LifeASSURE PDA filters to help lower bioburden and protect downstream purification skids.




 

Solutions for storing, shipping, and final fill

As mAb production scales, storage, handling, and fill-finish steps must support larger volumes while maintaining product integrity. Solutions, such as rigid support containers, versatile bioprocess containers (BPCs), and engineered fill-finish formats, help manage space, reduce handling risks, and support consistency in late-stage operations.

Nalgene low- and ultralow-particulate containers

Strengthen sterile storage and transport with Thermo Scientific Nalgene low- and ultralow-particulate containers that support particulate, endotoxin, and sterility requirements, particularly for large volumes.
 

Labtainer Pro BioProcess Containers

Support reliable handling of high-value liquids from 50 mL to 20 L with Thermo Scientific Labtainer Pro BioProcess Containers. Their films and format options help maintain containment during preparation, transfer, and storage.

Fill-finish


Use customizable fill-finish solutions for compounding, final filtration, and final fill. Single-use formats are designed to facilitate product integrity, meet lead-time requirements, and improve workflow efficiency.
 

Support across the entire workflow

As mAb production advances from preclinical into clinical and commercial phases, upstream and downstream volumes increase significantly. Scalable workflow solutions, including Thermo Scientific Powdertainer II Bioprocess Containers, fluid transfer assemblies, Thermo Scientific BioTitan Retention Device, ready-made buffers, process chemicals, dry powders, and media manufactured using Advanced Granulation Technology (AGT), help manage storage, transfer, and preparation needs. Sourcing services support flexible supply strategies that align materials with evolving requirements

Enable monoclonal antibody scale-up with media manufacturing

Scaling mAb production often requires media formats suitable for both development and full-scale manufacturing. Media manufacturing services enable transitions from non-GMP prototyping to the production of custom formulations at scale with tailored packaging. Format conversion and large-volume manufacturing capabilities help integrate custom solutions into existing workflows confidently.
 

Enhance liquid preparation with production and sourcing


Large-scale mAb production depends on steady access to process chemicals and efficient preparation steps. Production Chemicals and Sourcing Services offer cGMP-ready materials, sourcing support, supply chain management, and second-sourcing options that help address risk, operational efficiency, and total cost of ownership (TCO). Ready-to-hydrate powders, ready-to-use liquids, concentrates, and in-line dilution help reduce labor and space needs during buffer preparation.

Explore the 3D mAb workflow

Frequently asked questions

Scaling introduces higher buffer and media demands, increased storage needs, and expectations for consistency across batches. Teams must adapt early-stage productivity to larger volumes while maintaining cGMP requirements. Managing space, coordinating supply, and controlling process variability become increasingly important as production progresses

Upstream scale-up while maintaining productivity and consistent batch performance involves using scalable bioreactor platforms and automation, along with optimized media and feeds as volumes increase. Ease of transfer across vessel sizes from bench to production supports reproducible scale-up and helps teams meet milestones.

Clarification systems that manage larger volumes, followed by ProA capture and polishing with AEX, CEX, and HIC resins, support early impurity reduction. As volumes rise, buffer use and facility constraints can become limiting; chromatography platforms designed for higher throughput help maintain consistent purification outcomes.

Larger-scale operations require addressing storage, labor, and scheduling pressures. Ready-to-use or made-to-order (MTO) liquids help reduce footprint and preparation steps while supporting predictable supply planning. This approach can minimize operational burden and help avoid delays when buffer preparation becomes a bottleneck in large-scale operations.

Detecting low-level impurities is important during scale-up. Upstream tools help identify mycoplasma, while downstream workflows focus on residual DNA, proteins, and viral contaminants. Using PCR and dPCR methods helps achieve low limits of quantification (LOQ) and effectively meet compliance requirements.

Viral inactivation is positioned between capture and polishing. It typically involves holding the mAb drug substance at low pH for 30–60 minutes, then neutralizing with a base. Because low pH can induce aggregation, gentle mixing and defined buffers help maintain product integrity at scale.

Single-use technologies help reduce space, cleaning, and buffer preparation demands. The DynaDrive System supports higher volumes in a smaller footprint. The DynaSpin Centrifuge can lessen process liquid and filter use. The DynaChrom System enables in-line dilution and concentrate usage to reduce buffer preparation and storage needs during commercial production.

When handling the final stages of mAb drug substance and product, container durability and compatibility with sterilized operations help maintain product safety. Single-use BPCs, engineered fill-finish formats, and low-particulate bottles support consistency and reduce handling risk as drug substance moves through processing and distribution steps.

Supporting other therapeutic antibody development

Thermo Fisher also supports the development and manufacturing of additional therapeutic antibody modalities, including antibody-drug conjugates (ADCs) and bispecific antibodies (bsAbs). Explore these modalities within the broader bioprocessing applications framework.

Antibody-drug conjugates (ADCs)

Support ADC development with solutions built to streamline antibody production, conjugation-ready purification, and analytical workflows that help maintain product quality.
 

Bispecific antibodies (BsAbs)

Advance bsAb development with solutions that support complex molecule expression, purification strategies that manage chain pairing, and analytical tools that help evaluate product quality and consistency.

For Research Use or Further Manufacturing. Not for diagnostic use or direct administration into humans or animals.