As a process development scientist specializing in monoclonal antibody (mAb) purification with over 15 years of experience optimizing downstream platforms, I frequently encounter the practical question from colleagues and clients:

"Our standard Capto™ Adhere process already achieves acceptable purity in flow-through mode — under what specific circumstances does it truly justify switching to (or designing in) the ImpRes variant?"

In 2026, with increasingly stringent regulatory expectations for aggregate control (often <0.5–1% HMW species in final drug substance), tighter HCP/DNA/virus clearance requirements, and the growing adoption of intensified and two-step purification schemes, this decision has become more nuanced — and more economically consequential.

Both resins share the same multimodal ligand chemistry — N-benzyl-N-methyl ethanolamine — providing the signature combination of strong anion exchange, hydrophobic, and hydrogen-bonding interactions that has made Capto™ Adhere a workhorse for post-Protein A polishing since the mid-2010s. The critical differentiator lies in bead size and the resulting chromatographic performance.

Key Physicochemical and Performance Differences

The ~40 μm bead size is the decisive engineering upgrade: it reduces intraparticle mass transfer limitations, yielding narrower elution bands and better discrimination between monomer and closely eluting impurities (aggregates, clipped variants, or charge isoforms).

When Standard Capto™ Adhere Remains the Optimal Choice

In my experience across dozens of mAbs (including IgG1, IgG4, and several bispecific formats), the standard version continues to dominate early-to-mid clinical and many commercial processes when:

1. Aggregate burden post-Protein A is moderate (<4–6%) and readily cleared to <1% in flow-through mode under standard conditions (e.g., pH 5.0–5.8, conductivity 15–25 mS/cm).

2. The platform delivers consistent >98.5% monomer, acceptable HCP (<10–50 ppm), DNA (<10 pg/mg), and viral clearance (>4–5 LRV) without yield erosion.

3. High loading (>60–100 g/L) and high linear velocities are prioritized to maximize productivity and minimize buffer consumption.

4. Process economics are paramount — particularly for biosimilars, high-titer commercial products, or early-phase material where resin cost and column cycling efficiency dominate COGS.

5. The molecule exhibits “well-behaved” binding/elution characteristics with minimal peak tailing or resolution challenges on the 75 μm beads.

Most contemporary MabSelect PrismA™ → low-pH VI → Capto™ Adhere FT → VF/UF/DF platforms still achieve Phase 3 and commercial specifications using the standard resin.

When Upgrading to Capto™ Adhere ImpRes Provides Clear Value

Switch to (or develop with) the high-resolution ImpRes variant when analytical or process data reveal one or more of the following bottlenecks:

1. Persistently high or “difficult” aggregates (>6–10% in Protein A eluate, or molecules with elevated surface hydrophobicity, tendency to form stable dimers/oligomers that partially co-elute in FT mode).

2. Requirement for separation of charge variants or subtle product-related impurities (e.g., deamidated/acid variants, C-terminal lysine variants) — ImpRes frequently enables baseline or near-baseline resolution in shallow gradients.

3. Bind/elute mode is strategically preferred — for tighter control over elution pool volume, reduced buffer use, higher step yield at ultra-high purity, or when FT mode cannot meet aggregate specs without excessive loading restrictions.

4. Late-phase/commercial pressure for tighter purity specifications — aggregate <0.5%, HCP <5–10 ppm, or exceptional virus clearance in minimal steps.

5. Aspiration for a robust two-column process — numerous case studies (including bispecific antibodies) demonstrate that Capto™ Adhere ImpRes in B/E mode, following a high-capacity Protein A capture (e.g., MabSelect PrismA™ or MabSelect VL™), can deliver commercial-grade purity and >4–5 LRV virus reduction as a single polishing step.

6. Poor chromatographic performance on standard resin — broad/tailing peaks, incomplete aggregate rejection, or yield loss due to overlapping monomer–impurity windows.

In head-to-head studies, ImpRes consistently demonstrates:

· Higher monomer yield at equivalent purity in B/E mode

· Lower elution pool volumes (fewer CVs)

· Robust aggregate clearance even at higher loads or shorter residence times

· Better overall impurity resolution

Practical Decision Framework

Use this streamlined logic tree:

· Aggregate challenge severe (>6–8% or stubborn dimers/FT fails to clear <1%)? → Strongly favor ImpRes

· Need charge variant enrichment/reduction or ultra-low HMW in final DS? → ImpRes (B/E mode)

· Flow-through mode sufficient + cost/productivity paramount? → Standard Capto™ Adhere

· Late-phase/commercial with tight specs + budget allows 20–50% resin premium? → ImpRes

· Early clinical/platform/high-throughput screening? → Start with standard; switch only if resolution fails

A common successful strategy in 2025–2026 development programs is parallel scouting: run platform FT on standard Capto™ Adhere for robustness data, while simultaneously evaluating ImpRes in B/E mode for potential process intensification or impurity “insurance.”

Final Verdict from the Bench

Capto™ Adhere ImpRes is not an obligatory replacement — it is a precision tool for the ~20–40% of molecules/processes where resolution becomes the rate-limiting step.

If your current standard Capto™ Adhere process robustly meets all specifications with attractive economics, there is rarely a compelling scientific or regulatory reason to change.

However, when aggregates prove refractory, charge heterogeneity demands attention, bind/elute polishing offers strategic advantages, or you are pushing for a lean two-step process with maximum yield at exceptional purity — the ~40 μm high-resolution beads of ImpRes frequently deliver the decisive performance edge that more than justifies the incremental resin cost.

In an era of ever-tightening quality targets and cost-of-goods pressure, having ImpRes in your toolbox is increasingly viewed as prudent risk mitigation rather than luxury.