Feature article - Agarose resins: Accelerating advanced biologics and cell and gene therapies

Agarose resins, once confined to the lab, are now essential to biopharmaceutical manufacturing. Carolina Egea, general manager of Agarose Bead Technologies explores their evolution 

Two and a half decades ago, agarose resins - commonly referred to as chromatography beads - were primarily used in research laboratories to isolate proteins, purify biomolecules, and investigate cellular and molecular processes. Their value in science was clear, but their application remained confined to analytical and small-scale work.

The growth of biotechnology fundamentally reshaped these expectations. With the rise of monoclonal antibodies (mAbs), recombinant proteins and, more recently, cell and gene therapies, the industry required purification materials capable of transitioning seamlessly from research to large-scale industrial manufacturing. Agarose resins evolved accordingly, becoming high-performance, GMP-ready chromatography media that now underpin global biologics production.

Today, leading biopharmaceutical manufacturers depend on agarose resins to deliver safe, consistent and efficient downstream purification at industrial volumes, often reaching thousands of litres. The transformation of these resins mirrors the evolution of the biotech sector itself from an exploratory, research-driven field to one characterised by precision engineering and robust GMP biomanufacturing.

Three pillars of performance

As bioprocessing has scaled, the expectations placed on chromatography materials have intensified. High-performance agarose resins must now deliver three essential attributes: scalability, reproducibility and sustainability.

Purification processes that once handled milligram quantities must now operate at pilot and commercial manufacturing scales.1 This demands chromatography media with mechanically stable agarose matrices, controlled bead porosity and pore size distribution, reliable pressure–flow behaviour and robust chemical stability over repeated cycles

These properties ensure that performance observed during process development translates consistently to manufacturing-scale columns without compromising resolution, capacity or throughput.

The regulatory framework surrounding biopharmaceuticals has tightened significantly, with regulators across the US, Europe and the rest of the world regularly issuing key updates in response to the increasing complexity of biologics and advanced therapies.2 Their manufacturing processes must meet stringent quality, traceability and consistency requirements to support GMP bioprocessing.

To achieve this, resin manufacturers have implemented highly controlled production workflows, validated analytical characterisation, documented supply chain traceability and rigorous lot-to-lot consistency programmes. These practices ensure reliable process performance and compliance with global regulatory expectations.

As biomanufacturers pursue lower resource consumption and more environmentally responsible operations, resin producers are optimising their processes to reduce solvent use, minimise waste streams and extend resin operational lifetimes. This focus is critical because downstream purification typically accounts for a significant percentage of total process water consumption.3 By improving yield and reducing the total cost of purification, sustainable processes can also provide economic benefits.

Scaling infrastructure to support demand

The evolution of agarose resin manufacturing over the past 25 years reflects the rapid growth and increasing sophistication of the biopharmaceutical industry itself. As demand for biologics and advanced therapies has increased, resin producers have faced pressure to deliver materials that are not only higher in quality and performance but also scalable, reproducible and more resource-efficient.

Meeting these rising expectations has required major innovation and sustained investment across the manufacturing landscape. Modern agarose resin facilities now combine automation, digitalisation and advanced analytical control to achieve the consistency and throughput required under GMP conditions.

• Advanced automation & digital process control: Resin production has moved from manual or semi-manual operations to digitally controlled, automated systems that maintain tight control over bead formation, cross-linking and functionalisation chemistry. This ensures consistent bead morphology, uniform ligand coupling and predictable performance across batches
• Integration of process analytical technology (PAT): The use of real-time analytical tools has strengthened process robustness and accelerated scale-up to commercial production. PAT enables manufacturers to continuously monitor key parameters, improving product quality assurance and the efficient use of raw materials and solvents
• Flexible & modular manufacturing systems: Producers increasingly employ modular manufacturing units and selected single-use components - rather than full single-use bioreactors - to improve operational flexibility, reduce cleaning requirements and minimise cross-contamination risks. These systems support rapid campaign changes and improved responsiveness to fluctuating global demand
• Enhanced quality control (QC) & analytical capabilities: Modern resin facilities feature expanded QC laboratories equipped with advanced analytical instrumentation. This allows for faster in-process control, shorter release times and a deeper understanding of product variability, which are key factors in maintaining regulatory compliance and global customer confidence. This analytical depth strengthens supply reliability and ensures global customers receive consistent, high-performance chromatography media
• Optimised filling, packaging & global logistics: Automated filling and packaging systems reduce human error and handling risks. At the same time, manufacturers are reinforcing logistics infrastructure - regional warehouses, redundant supply routes and cold-chain-compatible packaging where needed - to ensure uninterrupted global supply, an industry priority highlighted during the COVID-19 pandemic

Through these advances, agarose resin producers are building a more agile and reliable manufacturing base capable of supporting the biopharmaceutical industry’s continued expansion while meeting the stringent standards of modern GMP production.

Evolution of agarose resins

The diversity of today’s biologics - from mAbs and bispecifics to viral vectors and complex recombinant proteins - has driven a shift from off-the-shelf solutions to customised resin development. Purification challenges differ widely depending on

• Molecular size, shape and charge
• Aggregation behaviour
• Expression system (CHO, E. coli, yeast, insect cells)
• Impurity profile
• Regulatory & viral safety considerations

To address this, resin developers are increasingly working as strategic partners, collaborating closely with biopharmaceutical companies to co-develop affinity and ion exchange resins tailored to specific purification needs. Customisation may involve tuning ligand chemistry, bead porosity, mechanical strength or matrix architecture to optimise yield, selectivity and throughput.

This partnership-driven approach accelerates innovation: insights gained during bespoke projects often lead to improvements across broader resin platforms and next-generation chromatography media.

A sustainable and data-driven future for bioprocessing

Looking forward, agarose resin technology will play a central role in enabling more sustainable, scalable and accessible biologics manufacturing. Key areas of expected progress include:

• Greener synthesis routes and reduced solvent use
• Bio-based or lower-impact raw materials
• Extended resin lifetimes
• Circular manufacturing principles
• Digital traceability & predictive performance modelling

The evolution of agarose resins over the past quarter-century mirrors the trajectory of biotechnology itself from exploratory research to industrial-scale, precision-engineered biomanufacturing. As advanced therapies continue to grow, these chromatography materials will remain fundamental to the reliable, high-quality production of the world’s most sophisticated medicines.

References:

1. https://www.sciencedirect.com/science/article/pii/S002196731731703X 

2. https://www.openaccessjournals.com/articles/regulatory-issues-and-debates-in-modern-biomanufacturing-18051.html

3. https://www.sciencedirect.com/science/article/pii/S0021967324009191