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Efficiency in bispecific capture

Published date: 18 July 2025

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Purification might not be the glamorous side of bioprocessing. It’s not where Nobel Prizes are won. But if you’re wondering where your margins go, where timelines start to slip, or why your COGs chart keeps climbing, this is where to look.

It often starts with a promising molecule, decent expression titers, and the hope that purification won’t be the bottleneck. Then comes the capture step. That’s when the spreadsheet opens, and the real math begins.

Particularly when working with fragments, bispecifics, or anything else that doesn’t just simply pass through a Protein A column. Here, you’re in the territory of kappa and lambda light chain capture, which often means reaching for the less-celebrated Protein L.

The three faces of efficiency

The word gets used a lot: efficiency. It sounds like one of those tidy metrics that slots in next to throughput or yield on a dashboard. But in practice, efficiency is messier. It’s not a single metric; it’s a constellation of trade-offs.

Start with cost efficiency. Everyone’s chasing it: Lower resin costs, fewer buffers, faster turnovers. Small changes here scale quickly when you’re running multiple batches or working with high-volume reactors. Saving a few dollars per gram can add up to millions over a campaign, especially when those savings come with fewer consumables and simpler workflows.

Then there’s process efficiency. This one’s harder to fake. It’s about how much you can push through the system before things start to break, physically or statistically. High-flow resins help. So do predictable elution profiles and minimal downstream rework. The goal is more product in less time, without compromising purity or performance.

Finally, there’s operational efficiency. The one people usually notice only when it’s missing. It shows up when your resin gives out after 10 cycles, when sanitization cannot be done properly, or when column packing is a full-time job. It’s the friction in tech transfer, the cold-chain dependency, the column that doesn’t pass qualification. It’s not glamorous, but it’s often the difference between scalable and stuck.

A rethink

If you’ve been relying on Protein L for bispecific and fragment purification, you are already aware of the trade-offs. It’s great when it works. But when it doesn’t whether you’re working with lambda chains, managing harsh pH conditions, or aiming for more reusability, the limitations become clear.

That’s where Fabsorbent™ F1P HF quietly makes its case.

We’re not here to wave flags or make bold claims about ligands. But the downstream demands on antibody fragments are tough. Fabsorbent™ was designed to solve a specific problem: how do you purify complex antibody formats efficiently, without the usual cost, complexity, or compromise?

Built on a high-flow agarose matrix (PuraBead® 6HF, if you’re keeping track), Fabsorbent™ pairs fast-flow performance with a synthetic ligand that binds both kappa and lambda light chains. No bacterial components. No cold storage. No concerns about leachables or immunogenic risk.

It’s not magic, but it is built differently.

Capture it clean, keep it simple

Purification is one of those steps where a cleaner start makes everything that follows easier. That’s why capture matters, not just for yield but for what comes next. The fewer impurities you carry forward, the less polishing you need.

In a comparative run using an E. coli-derived Vκ fragment, Fabsorbent™ showed over 78% recovery, on par with a market leading Protein L resin. But where it really pulled ahead was host cell protein (HCP) clearance: 3.67 log PPM vs. 1.84 PPM. That’s not a rounding error, that’s a purification profile you can build a process on.

To add, Fabsorbent™ achieved this at a gentler elution pH (5.0 vs. 2.5), which means fewer headaches around product stability, reduced aggregation risks, and better compatibility with downstream analytics.

Less stress on the molecule, less stress on the team.

Cost, scaled

Here’s where things get real. Run the math on a 2000 L bioreactor with a 2 g/L titer. That’s a lot of protein, and a lot of cost decisions.

In direct cost terms, Fabsorbent™ came in slightly under the market-leading Protein L resin: $9.29 per gram vs. $9.57. That’s the quiet part. The loud part is what happens around that number.

Fabsorbent™ can handle more than 100 cycles. It doesn’t require cold storage. One NaOH-based cleaning protocol works across the board. Fewer buffers mean fewer prep steps, faster turnaround, and less chance for deviation. That’s where the cost advantage turns into process efficiency.

You don’t need to swap out infrastructure or train a new team. You just run more cycles, spend less time waiting, and stop wondering if your resin will hold up past cycle 15.

Built to flow

Efficiency, at its heart, is about time. Time in chromatography is measured in flow rates, cycles, and clean-in-place validation.

Fabsorbent™ doesn’t just tolerate fast flow. The PuraBead® base supports rates up to 500 cm/h without clogging, channeling, or hastle. For manufacturing sites looking to squeeze more throughput from the same equipment footprint, that matters.

It also performs well across a wide range of conditions. Process development teams have run design of experiments (DOE) studies across salt and pH gradients, and the resin held its ground, binding consistently even when buffers weren’t textbook-perfect. Acetate buffers around pH 5.5 gave the best balance between elution strength and product purity. But if you miss the target slightly, it still works.

That kind of process headroom matters when variability hits, because sooner or later, it will.

The operational side (the stuff that saves you later)

Operational headaches don’t usually show up in the pilot run. They show up in the 10th campaign, during tech transfer, or in the QA audit that asks why your resin only lasts 12 cycles or why your column requires repacking every batch.

Fabsorbent™ helps to avoid most of that. It’s chemically stable from pH 1.5 to 14, can be cleaned with 1.0 M NaOH, and holds up under pressure, both literally and figuratively. It’s stored at ambient temperature in 20% ethanol, no cold chain, no condensation issues, no shipping complications.

And if column packing is your bottleneck, Astrea Bioseparations can supply custom-packed Evolve® and Evolve®D columns that are pre-validated and ready to use. Less work, fewer variables, more control. Then just wait for your operations team to give you a high five.

The platform that isn't one

Here’s the irony. Everyone’s chasing “platform” processes for the flexibility they promise. But real flexibility doesn’t come from forcing every molecule through the same funnel. It comes from building tools that are adaptable by design.

Fabsorbent™ isn’t Protein A, and it’s not intended to platform every bispecific. But it does provide a dependable capture step for a wide range of asymmetric or fragment-based bispecifics, and it integrates smoothly into both batch and continuous processing setups.

It also runs on standard chromatography systems. No special analytics, no need to re-engineer your workflow. It just works, and keeps working.

The bottom line

This isn’t about chasing the latest buzzword in resin design. It’s about something simpler: doing more with less. More throughput with fewer steps. More cycles with less downtime. More flexibility with fewer compromises.

Fabsorbent™ F1P HF doesn’t promise miracles. It’s offering something rarer: quiet consistency, built-in resilience, and performance that helps processes scale instead of stall.

Because in the end, the best purification step is the one you don’t have to worry about.

 

Want to dig into more technical details? Find them in the white paper, here.

Resin featured in this blog: Fabsorbent™ F1P HF 

 

To find out more about our antibody toolbox solution, please reach out to us at sales@astrea-bio.com or visit our antibody webpage.

 

Interested in trying in your own workflow?

Experience the efficiency and reliability of these resins in your workflow. Whether you’re optimizing processes in research or manufacturing applications, our sample program allows you to evaluate performance in the context that matters most to you.

Request sample here.

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Efficiency in bispecific capture

Published date: 18 July 2025

Back to Article Listing

Purification might not be the glamorous side of bioprocessing. It’s not where Nobel Prizes are won. But if you’re wondering where your margins go, where timelines start to slip, or why your COGs chart keeps climbing, this is where to look.

It often starts with a promising molecule, decent expression titers, and the hope that purification won’t be the bottleneck. Then comes the capture step. That’s when the spreadsheet opens, and the real math begins.

Particularly when working with fragments, bispecifics, or anything else that doesn’t just simply pass through a Protein A column. Here, you’re in the territory of kappa and lambda light chain capture, which often means reaching for the less-celebrated Protein L.

The three faces of efficiency

The word gets used a lot: efficiency. It sounds like one of those tidy metrics that slots in next to throughput or yield on a dashboard. But in practice, efficiency is messier. It’s not a single metric; it’s a constellation of trade-offs.

Start with cost efficiency. Everyone’s chasing it: Lower resin costs, fewer buffers, faster turnovers. Small changes here scale quickly when you’re running multiple batches or working with high-volume reactors. Saving a few dollars per gram can add up to millions over a campaign, especially when those savings come with fewer consumables and simpler workflows.

Then there’s process efficiency. This one’s harder to fake. It’s about how much you can push through the system before things start to break, physically or statistically. High-flow resins help. So do predictable elution profiles and minimal downstream rework. The goal is more product in less time, without compromising purity or performance.

Finally, there’s operational efficiency. The one people usually notice only when it’s missing. It shows up when your resin gives out after 10 cycles, when sanitization cannot be done properly, or when column packing is a full-time job. It’s the friction in tech transfer, the cold-chain dependency, the column that doesn’t pass qualification. It’s not glamorous, but it’s often the difference between scalable and stuck.

A rethink

If you’ve been relying on Protein L for bispecific and fragment purification, you are already aware of the trade-offs. It’s great when it works. But when it doesn’t whether you’re working with lambda chains, managing harsh pH conditions, or aiming for more reusability, the limitations become clear.

That’s where Fabsorbent™ F1P HF quietly makes its case.

We’re not here to wave flags or make bold claims about ligands. But the downstream demands on antibody fragments are tough. Fabsorbent™ was designed to solve a specific problem: how do you purify complex antibody formats efficiently, without the usual cost, complexity, or compromise?

Built on a high-flow agarose matrix (PuraBead® 6HF, if you’re keeping track), Fabsorbent™ pairs fast-flow performance with a synthetic ligand that binds both kappa and lambda light chains. No bacterial components. No cold storage. No concerns about leachables or immunogenic risk.

It’s not magic, but it is built differently.

Capture it clean, keep it simple

Purification is one of those steps where a cleaner start makes everything that follows easier. That’s why capture matters, not just for yield but for what comes next. The fewer impurities you carry forward, the less polishing you need.

In a comparative run using an E. coli-derived Vκ fragment, Fabsorbent™ showed over 78% recovery, on par with a market leading Protein L resin. But where it really pulled ahead was host cell protein (HCP) clearance: 3.67 log PPM vs. 1.84 PPM. That’s not a rounding error, that’s a purification profile you can build a process on.

To add, Fabsorbent™ achieved this at a gentler elution pH (5.0 vs. 2.5), which means fewer headaches around product stability, reduced aggregation risks, and better compatibility with downstream analytics.

Less stress on the molecule, less stress on the team.

Cost, scaled

Here’s where things get real. Run the math on a 2000 L bioreactor with a 2 g/L titer. That’s a lot of protein, and a lot of cost decisions.

In direct cost terms, Fabsorbent™ came in slightly under the market-leading Protein L resin: $9.29 per gram vs. $9.57. That’s the quiet part. The loud part is what happens around that number.

Fabsorbent™ can handle more than 100 cycles. It doesn’t require cold storage. One NaOH-based cleaning protocol works across the board. Fewer buffers mean fewer prep steps, faster turnaround, and less chance for deviation. That’s where the cost advantage turns into process efficiency.

You don’t need to swap out infrastructure or train a new team. You just run more cycles, spend less time waiting, and stop wondering if your resin will hold up past cycle 15.

Built to flow

Efficiency, at its heart, is about time. Time in chromatography is measured in flow rates, cycles, and clean-in-place validation.

Fabsorbent™ doesn’t just tolerate fast flow. The PuraBead® base supports rates up to 500 cm/h without clogging, channeling, or hastle. For manufacturing sites looking to squeeze more throughput from the same equipment footprint, that matters.

It also performs well across a wide range of conditions. Process development teams have run design of experiments (DOE) studies across salt and pH gradients, and the resin held its ground, binding consistently even when buffers weren’t textbook-perfect. Acetate buffers around pH 5.5 gave the best balance between elution strength and product purity. But if you miss the target slightly, it still works.

That kind of process headroom matters when variability hits, because sooner or later, it will.

The operational side (the stuff that saves you later)

Operational headaches don’t usually show up in the pilot run. They show up in the 10th campaign, during tech transfer, or in the QA audit that asks why your resin only lasts 12 cycles or why your column requires repacking every batch.

Fabsorbent™ helps to avoid most of that. It’s chemically stable from pH 1.5 to 14, can be cleaned with 1.0 M NaOH, and holds up under pressure, both literally and figuratively. It’s stored at ambient temperature in 20% ethanol, no cold chain, no condensation issues, no shipping complications.

And if column packing is your bottleneck, Astrea Bioseparations can supply custom-packed Evolve® and Evolve®D columns that are pre-validated and ready to use. Less work, fewer variables, more control. Then just wait for your operations team to give you a high five.

The platform that isn't one

Here’s the irony. Everyone’s chasing “platform” processes for the flexibility they promise. But real flexibility doesn’t come from forcing every molecule through the same funnel. It comes from building tools that are adaptable by design.

Fabsorbent™ isn’t Protein A, and it’s not intended to platform every bispecific. But it does provide a dependable capture step for a wide range of asymmetric or fragment-based bispecifics, and it integrates smoothly into both batch and continuous processing setups.

It also runs on standard chromatography systems. No special analytics, no need to re-engineer your workflow. It just works, and keeps working.

The bottom line

This isn’t about chasing the latest buzzword in resin design. It’s about something simpler: doing more with less. More throughput with fewer steps. More cycles with less downtime. More flexibility with fewer compromises.

Fabsorbent™ F1P HF doesn’t promise miracles. It’s offering something rarer: quiet consistency, built-in resilience, and performance that helps processes scale instead of stall.

Because in the end, the best purification step is the one you don’t have to worry about.

 

Want to dig into more technical details? Find them in the white paper, here.

Resin featured in this blog: Fabsorbent™ F1P HF 

 

To find out more about our antibody toolbox solution, please reach out to us at sales@astrea-bio.com or visit our antibody webpage.

 

Interested in trying in your own workflow?

Experience the efficiency and reliability of these resins in your workflow. Whether you’re optimizing processes in research or manufacturing applications, our sample program allows you to evaluate performance in the context that matters most to you.

Request sample here.

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