MONOCLONAL ANTIBODIES

CaptureSMB® — Continuous Capture Chromatography for mAbs

Twin-column Protein A capture for mAb manufacturing. Load Protein A to its true capacity — and keep it there, cycle after cycle. Validated from lab to GMP production scale by Bristol Myers Squibb at 100× scale-up: 2.5× Productivity | 92% Resin utilisation (vs. 67% batch) | 50% less buffer | ≥94% Yield (equivalent to batch)

Source: Angelo et al., BioProcess International 2018; Müller-Späth et al., Biotechnol. Bioeng. 2019 (Bristol Myers Squibb)

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Download the mAb Application Note

Talk to Our mAb Specialists

Download the mAb Application Note

The Protein A Capture Bottleneck

Monoclonal antibodies dominate the biopharmaceutical market — with 100+ approved products, a rapidly growing biosimilar wave, and expanding next-generation formats (bispecifics, ADCs, Fc-fusion proteins). Downstream purification must keep pace.

The Protein A affinity capture step is the cornerstone of mAb downstream processing — but conventional batch chromatography is inherently inefficient. Columns are loaded conservatively to only 50–70% of the resin’s dynamic binding capacity, leaving expensive Protein A resin underutilized. Long sequential cycle times (load → wash → elute → regenerate → re-equilibrate) create idle column time, limiting throughput and inflating facility footprint.

With cell culture titers now routinely exceeding 5–15 g/L and perfusion bioreactors demanding continuous feed processing, the batch capture step is the rate-limiting bottleneck in modern mAb manufacturing.

The Solution: CaptureSMB® with AutomAb® for mAb Capture

CaptureSMB® is an optimized twin-column periodic countercurrent (PCC) process for continuous Protein A capture of monoclonal antibodies and antibody variants. Two identical columns operate in coordinated interconnected and parallel phases — maximizing resin utilization by safely loading well beyond the breakthrough point, while the second column captures any product that breaks through. The result: 2.5× higher productivity (BMS-demonstrated), 92% resin utilization (vs. 67% batch), and 50% buffer savings compared to batch.

AutomAb® dynamic process control uses in-line UV sensors at each column outlet to monitor the breakthrough curve in real-time, automatically adjusting the interconnected loading duration to compensate for feed titer variability, column aging, and batch-to-batch variation — ensuring robust, unattended 24/7 continuous capture.

Same resin. Same buffers. Superior performance. CaptureSMB works with all major Protein A resins — MabSelect SuRe, MabSelect PrismA, Amsphere, and others — and uses your existing wash, elution, regeneration, and CIP buffers unchanged. Your current batch conditions are the starting point; CaptureSMB® is developed from there. Only two columns required — the simplest PCC configuration available.

Learn About CaptureSMB® with AutomAb®

Proven Results: CaptureSMB® vs. Batch – Protein A Capture – mAb

2.5×

Productivity Increase
8.4 → 26.5 g/L/h

92%

Resin Utilization
vs. 67% batch

50% ↓

Buffer Reduction
0.73 → 0.34 L/g

≥94%

Yield Maintained
Consistent at both scales

24/7

Continuous Operation
Perfusion-ready

100×

Scale-Up Validated
CUBE → TWIN (BMS)

Industry Validation: Bristol Myers Squibb (BMS)

Bristol Myers Squibb — one of the world’s largest biopharmaceutical companies — has systematically validated CaptureSMB from laboratory through GMP pilot and production scale in a landmark series of peer-reviewed publications (2018–2021), establishing the regulatory and scientific foundation for industrial adoption of continuous mAb capture.

BMS CaptureSMB milestones:

Lab-to-GMP Scale-Up (2018): Seamless 100× scale-up from Contichrom CUBE to Contichrom TWIN with consistent yield ≥94% and comparable product quality
Process Characterization for FDA Filing (2019): Model-assisted validation reduced experimental effort ~87% while meeting FDA process validation guideline requirements
Viral Clearance Validated (2019, 2021): cGLP studies confirmed CaptureSMB LRVs comparable to batch Protein A; validated surrogate model simplifies future filings
Integrated Continuous Downstream (2020): CaptureSMB combined with automated viral inactivation and pool-less polishing into a semi-continuous process for multiple mAbs

Sources: Angelo, Pagano, Müller-Späth et al., BioProcess International 16(4), 2018; Baur, Angelo et al., Biotechnol. Bioeng. 116(1), 2019; Angelo et al., Biotechnol. Bioeng. 116(9), 2019; Angelo, Potter, Müller-Späth et al., Biotechnol. Bioeng. 118(9), 2021; Xu, Angelo et al., mAbs 12(1), 2020

Case Study 1: Scale-Up – Lab to Production

Molecule: IgG4 mAb (5 g/L titer, MabSelect SuRe LX Protein A) Scale: 100× — Contichrom CUBE (1.0 cm i.d.) → Contichrom TWIN (10.0 cm i.d.) Validation Partner: Bristol Myers Squibb

Parameter	Batch Reference	CaptureSMB (Run 2, optimized)
Yield	≥94%	≥94% — consistent at both scales
Productivity	8.4 g/L/h	26.5 g/L/h (+2.5×)
Capacity Utilization	67%	92%
Buffer Consumption	0.73 L/g	0.34 L/g (−50%)
Product Quality	HCP 447 ppm, HMW 3.0%	Comparable — HCP 500 ppm, HMW 2.9%

Key finding: CaptureSMB transferred seamlessly from CUBE to TWIN at 100× scale with no systematic CQA deviations across cycles. Resin utilization reached 92% (vs. 67% batch), and productivity increased 2.5× — enabling smaller columns and shorter campaigns for the same output.

Angelo, J., Pagano, J., Müller-Späth, T. et al. BioProcess International, 16(4), 28–37 (2018)

Case Study 2: Process Characterization & Validation

Molecule: IgG4 mAb (tested across 1–12 g/L titer range, MabSelect SuRe LX Protein A) Equipment: Contichrom CUBE Regulatory Framework: FDA Process Validation Guideline (Stage 1), ICH Q8

Validation Approach	Experimental Runs	Outcome
Standard DoE	77 required (6-parameter CCD)	Only 22 of 77 feasible
Model-Assisted	10 selected (3-parameter CCD + Pareto)	All 10 feasible and optimal
Hybrid	Reduced (model pre-screens)	Infeasible points eliminated in silico

Key finding: A validated chromatographic model reduced experimental effort ~87% while delivering superior process understanding (<10% deviation from predictions). CQAs showed no dependence on CaptureSMB loading parameters — providing a regulatory roadmap for FDA filing.

Baur, D., Angelo, J., Chollangi, S., Müller-Späth, T. et al. Biotechnol. Bioeng., 116(1), 87–98 (2019). DOI: 10.1002/bit.26849

Case Study 3: Viral Clearance Validation

Molecule: IgG4 mAb (CHO-derived, MabSelect SuRe LX Protein A) Equipment: Contichrom CUBE Combined (CaptureSMB) + ÄKTA Avant (batch/surrogate) Study Type: cGLP viral clearance — X-MuLV (enveloped) + MVM (non-enveloped)

Parameter	Batch Protein A	CaptureSMB (cyclic steady state)
X-MuLV Clearance	5.11 LRV	~4–5 LRV — steady state by cycle 2
MVM Clearance	2.44 LRV	~2.5 LRV — consistent within ±0.5 LRV
Surrogate Model	—	5.03 / 2.54 LRV — matches steady state using batch equipment
Virus Carryover	—	Eliminated with 15-min CIP hold

Key finding: CaptureSMB viral clearance was comparable to batch Protein A for both virus models. A validated surrogate model using standard batch equipment (two columns in series) enables viral validation at any cGLP lab without continuous chromatography hardware.

Angelo, J., Chollangi, S., Müller-Späth, T. et al. Biotechnol. Bioeng., 116(9), 2275–2284 (2019). DOI: 10.1002/bit.27012 Angelo, J.M., Potter, K., Müller-Späth, T. et al. Biotechnol. Bioeng., 118(9), 3604–3609 (2021). DOI: 10.1002/bit.27674

mAb Purification Comparison Table:

Parameter	Batch Protein A Capture	CaptureSMB® with AutomAb®
Resin Utilization (DBC)	67% — conservative loading to avoid breakthrough	92% — safe overloading with second column capture
Productivity	8.4 g/L/h — limited by sequential cycle times and idle time	26.5 g/L/h — 2.5× higher, continuous loading eliminates idle time
Buffer Consumption	0.73 L/g — large column volumes drive buffer needs	0.34 L/g — 50% reduction from smaller columns
Product Yield	≥94% typical	≥94% — equivalent to batch
Product Quality (HCP, Agg, DNA)	HCP 447 ppm, HMW 3.0%	Comparable — HCP 500 ppm, HMW 2.9%
Feed Titer Sensitivity	Conservative timing — requires fixed load volumes	AutomAb® dynamically adjusts to titer variability
Column Aging	Fixed load parameters, performance degrades over lifetime	AutomAb® compensates for capacity loss in real-time
Perfusion Compatibility	Batch cadence mismatched with continuous feed	Ideal — continuous loading matches perfusion output directly
Hardware Complexity	Single column, simple	Two columns — simplest PCC configuration
Process Control	Manual monitoring or timer-based	Automated UV-based PAT (AutomAb®)
Stationary Phase / Buffers	Standard Protein A	Same — no change required

The Contichrom® Platform: From mAb Development to Production

All Contichrom systems support twin-column continuous chromatography with the Protein A, CEX, AEX, HIC, and mixed-mode resins used in mAb purification. Methods scale predictably from CUBE → TWIN LPLC.

Systems Overview

Contichrom® CUBE

The essential platform for chromatography process development. This versatile 100-bar benchtop FPLC system runs batch, integrated batch, and continuous chromatography — including MCSGP and CaptureSMB — out of the box. Develop purification processes for mAbs, peptides, oligonucleotides, ADCs, and viral vectors, with verified scale-up at over 100× to pilot and production systems.

Contichrom® TWIN LPLC – Capture

Accelerate biopharmaceutical capture chromatography at production scale. This sanitary GMP system uses CaptureSMB® with AutomAb® to maximize resin utilization — achieving up to 3× faster processing and 50% less Protein A resin and buffer consumption compared to batch. CIP-ready design for mAbs, viral vectors, ADCs, and recombinant proteins.

Contichrom® TWIN LPLC – Polishing

Bring continuous polishing to biopharmaceutical manufacturing at production scale. This sanitary GMP system uses MCSGP with AutoPeak® to eliminate the yield-purity trade-off achieving +10–50% absolute yield increase at target purity while reducing buffer consumption compared to batch. CIP-ready design for mAbs, viral vectors, ADCs, and recombinant proteins.

Systems Overview

mAb & Antibody Variant Applications

Monoclonal Antibodies (IgG1, IgG2, IgG4)

CaptureSMB® delivers 2.5× higher Protein A capture productivity for all IgG subtypes while maintaining ≥94% yield and comparable product quality (HCP, aggregates, DNA). Validated at 100× scale by Bristol Myers Squibb across multiple molecules.

Biosimilar mAbs

Biosimilar manufacturers face intense cost pressure. CaptureSMB’s 2.5× higher productivity and 50% buffer savings directly lower Cost of Goods — a critical competitive advantage in the biosimilar market where product differentiation occurs through manufacturing efficiency.

Bispecific Antibodies

Bispecific formats present unique downstream challenges (homodimer removal, charge variants). CaptureSMB® maximizes capture step efficiency, freeing capacity for the more complex polishing steps required. MCSGP continuous polishing on the same Contichrom platform can further resolve closely related bispecific variants.

Antibody Fragments (Fab, F(ab’)₂, scFv, VHH/Nanobodies)

Antibody fragments can be captured using Protein L, Protein A (for Fc-containing fragments), or custom affinity resins. CaptureSMB® has been demonstrated for F(ab’)₂ fragment capture using Protein L (KappaSelect) in twin-column countercurrent mode (Ulmer et al. 2015), delivering the same productivity and resin utilization gains as for full-length mAbs.

mAb & Antibody Variant Applications Continued….

Fc-Fusion Proteins

Fc-fusion proteins (e.g., etanercept, abatacept) are captured via Protein A affinity. CaptureSMB® continuous capture applies directly — maximizing resin utilization and throughput for this growing therapeutic class.

Perfusion-Coupled Continuous Manufacturing

CaptureSMB’s continuous loading mode is ideally matched to perfusion bioreactor output. By coupling CaptureSMB® directly to the bioreactor harvest, manufacturers achieve true end-to-end continuous biomanufacturing — reducing facility footprint, eliminating large harvest hold tanks, and shortening manufacturing cadence.

mAb Polishing with MCSGP

For charge variant, aggregate, or fragment separations that require gradient polishing (CEX, HIC), MCSGP continuous polishing on the same Contichrom platform eliminates the purity-yield trade-off — increasing polishing yield while maintaining target CQA specifications (Müller-Späth et al. 2008, 2010).

Learn About MCSGP® with AutoPeak®

Getting Started with mAb CaptureSMB®

See the Contichrom® platform in action before you commit, assess CaptureSMB® suitability from your existing batch Protein A data — computationally or experimentally — develop your continuous capture process at lab scale on a Contichrom® CUBE, then transfer to the TWIN LPLC for GMP production. BMS have validated 100× scale-up with 2.5× productivity and 50% buffer savings.

See It First — Free Demo or Webinar

Not yet familiar with the Contichrom® platform? Start here. YMC ChromaCon offers no-charge demonstrations and introductory webinars tailored to your team.

On-site in Zurich (half day, 2–4 hours): see the CUBE in person, run ChromIQ® live, discuss your mAb capture process with YMC ChromaCon application scientists
Remote webinar (1–3 hours): interactive live session covering CaptureSMB®, MCSGP, N-Rich®, ChromIQ® software, and the full Contichrom® ecosystem
Sessions cover CaptureSMB® process design, the AutomAb® control concept, and scale-up to TWIN LPLC manufacturing

→ Request a free demo or introductory webinar

Modeling Assessment for mAbs

Predict CaptureSMB® performance on your Protein A step before running any new experiments. YMC ChromaCon builds a calibrated mechanistic model from your existing batch data.

Submit your batch Protein A method (column dimensions, resin, buffers, flow rate) and breakthrough curve data — from any HPLC or FPLC system, no Contichrom® required
YMC ChromaCon builds the model, simulates CaptureSMB® operating points, and delivers a predicted batch vs. continuous performance comparison: productivity gain, resin utilization, and buffer savings — with scale-up parameters
AutomAb® dynamic control impact is included in the simulation
Typical timeline: 3–5 weeks from receipt of data; no material shipment required

→ CaptureSMB® Process Modeling Service

Experimental Feasibility Study — Your mAb, Your Resin

Your molecule is run on YMC ChromaCon’s Contichrom® platform at our facility in Zurich. We reproduce your batch Protein A method as a benchmark and run ≥ 3 CaptureSMB® experiments side-by-side.

Ship starting material to Zurich — typically ≥ 20× a single preparative batch run, scaled to 1 cm i.D. columns
We reproduce your analytical HPLC method, establish the batch benchmark, and run CaptureSMB experiments using your Protein A resin and buffers
Deliverable: side-by-side batch vs. CaptureSMB® comparison with real chromatographic data from your molecule, plus purified fractions for your independent verification
Typical timeline: 4–6 weeks after receipt of starting material and purchase order

→ YMC ChromaCon Feasibility Studies

Develop at Lab Scale — Rent or Purchase a CUBE

CaptureSMB® method development is performed on the Contichrom CUBE using your existing Protein A resin and buffer system. Available for rental or purchase.

ChromIQ® CaptureSMB® Wizard converts your breakthrough curve data into an initial CaptureSMB® operating point — the first continuous capture run is typically achievable within a day
Your current batch Protein A conditions are the starting point — no new resin or buffer development required
AutomAb® dynamic process control is configured to compensate for feed titer variability, column aging, and batch-to-batch variation — enabling robust, unattended 24/7 continuous capture
MCSGP polishing for downstream charge variant or size variant separation can also be developed on the same CUBE

→ Contichrom® CUBE Rental Program

→ Purchase a Contichrom® CUBE

Scale to GMP Production — Contichrom® TWIN LPLC

The CaptureSMB® process transfers directly from the CUBE to the TWIN LPLC for pilot and manufacturing-scale production. YMC ChromaCon provides scale-up consulting and GMP documentation support.

TWIN LPLC Capture for continuous Protein A capture with AutomAb® at pilot and production scale
TWIN LPLC Polishing (optional) adds downstream MCSGP for charge variant or size variant purification on the same platform family
Four TWIN LPLC system sizes (300–2000) cover 0.03–3.33 L/min up to 0.5–36 L/min — pilot through full GMP production
BMS validated 100× scale-up from CUBE to TWIN: 2.5× productivity, 92% resin utilization, 50% buffer savings, yield maintained ≥ 94%
GMP documentation support (IQ/OQ/PQ) and scale-up consulting available

→ Scale-Up Consulting and Training

01 / 05

Ready to Intensify Your mAb Purification Process?

Book a CUBE Rental Register for the Continuous Chromatography Workshop

How does CaptureSMB® increase Protein A productivity?

CaptureSMB® uses two columns in coordinated interconnected and parallel phases. While one column loads beyond the batch breakthrough point, the second captures any product that breaks through. This maximizes resin utilization (up to 92% DBC vs. 50–70% batch) and eliminates column idle time — delivering 2.5× higher productivity with smaller columns.

Does CaptureSMB® work with my existing Protein A resin and buffers?

Yes. CaptureSMB® works with all major Protein A resins — MabSelect SuRe, MabSelect PrismA, Amsphere JWT-203, and others — and uses your existing wash, elution, regeneration, and CIP buffers unchanged. The ChromIQ® CaptureSMB Wizard converts your batch breakthrough data into a continuous process.

Has CaptureSMB® been validated at production scale?

Yes. Bristol Myers Squibb validated CaptureSMB® from lab (Contichrom CUBE) to GMP pilot/production scale (Contichrom TWIN) with 100× scale-up, demonstrating consistent yield ≥94%, comparable product quality, and equivalent viral clearance — published in BioProcess International (2018) and Biotechnology and Bioengineering (2019, 2021).

Does CaptureSMB® clear viruses as effectively as batch Protein A?

Yes. Two cGLP viral clearance studies by Bristol Myers Squibb demonstrated that CaptureSMB achieves log reduction values (LRVs) for both retrovirus (X-MuLV) and parvovirus (MVM) comparable to standard batch Protein A chromatography. A validated surrogate model simplifies viral validation for regulatory filing.

How does AutomAb® handle feed titer variability?

AutomAb® uses in-line UV sensors at each column outlet to monitor the Protein A breakthrough curve in real-time. It dynamically adjusts the interconnected loading duration based on the actual breakthrough profile — compensating for batch-to-batch titer variation, column aging, and feed quality changes without manual intervention.

Can CaptureSMB® integrate with perfusion bioreactors?

Yes. CaptureSMB’s continuous loading mode is ideally suited for coupling with perfusion bioreactor output. Continuous feed processing eliminates the need for large harvest hold tanks and matches capture cadence to bioreactor output — enabling end-to-end continuous biomanufacturing as demonstrated by Bristol Myers Squibb.

How does CaptureSMB® compare to 3- and 4-column PCC systems?

CaptureSMB® uses only two columns — the simplest PCC hardware configuration. Modeling studies show it delivers equivalent or superior performance to 3- and 4-column PCC systems across a wide range of production scenarios (Baur et al., Biotechnol. J. 2016). Fewer columns means simpler validation, lower hardware cost, and easier operation.

Can Contichrom systems run both capture and polishing?

The Contichrom CUBE systems run CaptureSMB® (continuous capture), MCSGP (continuous polishing), batch, and 2D/3D integrated batch on the same hardware. The TWIN LPLC – Capture is dual-mode (CaptureSMB + batch/2D integrated batch) on a single skid — with options for sequential pool-less polishing and buffer in-line dilution. The TWIN LPLC – Polishing is dual-mode (MCSGP + batch/2D integrated batch) on a single skid.