Questions to ask when choosing a resin in process development

Jakob Liderfelt
Global Product Manager Resin and Technologies

Selecting the right chromatography resin is crucial for efficient purification of biopharmaceuticals. This article serves as a comprehensive checklist, guiding you through the essential factors to consider in your decision-making process. From understanding purification techniques and evaluating resin formats to ensuring regulatory compliance and sustainability, we cover all the key aspects. Whether you are purifying monoclonal antibodies, viral vectors, or other therapeutic molecules, this guide will help you navigate the complexities of resin selection and optimization for a successful biomanufacturing process.

Click on each topic of the checklist below to access the related information

Technique
Resin selection
Process development formats
Resin scalability
Resin cleaning and sanitization
Process economy
Security of supply
Quality and regulatory support
Sustainability
Scientific expertise
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1. Which techniques should I use to purify my molecule?

Before selecting a purification resin, you must know which chromatography techniques you will use and how you will combine them to optimize your purification protocol to obtain the right balance between purity and yield.

Planning to purify a mAb?

A typical mAb purification scheme starts with an affinity chromatography step, followed by two polishing steps: a cation exchange step and an anion exchange (AIEX) step. But if you don’t achieve the separation that you need (e.g., if you face aggregation issues, or have difficulties separating charge variants), you might need to evaluate other polishing techniques, as described in this quick start guide.

Planning to purify viral vectors?

A typical viral vector purification scheme starts with an affinity chromatography step, followed by an anion exchange chromatography step as described in this infographic. The key is to achieve high purity and yield of full capsids; if you cannot reach the performance you need, you will need to optimize the conditions and the protocol. This can be true for both the affinity step (though less often, since it typically works well) and the AIEX step.

Our handbook Strategies for purification describes how to design a protein purification procedure, and how to select and combine chromatography methods and purification formats.

2. What resins are best for each chromatography step?

So many resins to choose from. Here we have gathered resources for you to easily find the resins that are optimal for your capture and polishing processes.

Our resin guidance for mAbs and antibody variants:

Our resin guidance by technique:

Once you have identified a short list of suitable resins for your chromatography step, you can run screening studies to narrow down your options and optimize your processes.

3. Is the resin available in formats that support current process development methods?

The quality-by-design (QbD) initiative by the FDA puts additional demands on process development work, because it requires a higher degree of process understanding. Smart process development methods can accelerate development and improve general process understanding, robustness, and performance. But using them requires the use of resins in compatible formats.

Here are some examples:

If you plan on doing high-throughput screening, the resin must be available in multiwell plates and or robotic column formats.
If you use mechanistic modeling in your process development work, choose a resin that’s available in pre-characterized columns. This will save time and increase the accuracy of your model.
Use a resin kit designed for raw material variability studies, if you plan to conduct such studies during process characterization .

Read guidance on Selecting chromatography formats for your process development workflow to learn more.

4. Is the resin suitable for large-scale GMP manufacturing?

When you’re in the lab working with small volumes, it can be hard to envision the volumes needed for large-scale manufacturing. But keeping your ultimate goal in mind can save you time later. Make use of resources on how to scale a chromatography operation so you’ll be aware of what parameters are scalable and what will change as you scale.

For example, if you plan to pack your columns in house, ask whether the resin is designed for packing in large columns with maintained performance — and, along those lines, whether the resin is supplied with clear packing instructions.

On the other hand, if you plan on prepacked columns (i.e., columns packed by the resin supplier), make sure the resin is available in the dimensions you need to support you throughout scale up.

5. How does the resin stand up to cleaning and sanitization?

Cleaning-in-place (CIP) of chromatography resins is important for the integrity and safety of the final biopharmaceutical product. If your resin and ligand are incompatible with your cleaning and sanitization procedures, you’ll get less out of your resin before it needs to be replaced.

Learn how to evaluate resins for cleaning stability and set up CIP protocols for process and cost efficiency:

6. Is this the right resin for now and for the future process economy?

Different stages of drug development have different needs. A resin that’s “good enough” during an early stage may not stand up to the stringent requirements of later clinical phases, while a long-lifetime resin may be over-engineered for some early processes. It’s important to make use of methods to evaluate how productive your process setups will be in the large scale and how different choices effect process economy.

Additional readings:

Download our guide for protein A capture resins
Our Process Intensifier app enables you to plug in your process parameters for your capture step (including manufacturing stage, number of batches, and titer) and see the impact of different choices on your outcomes.

7. What is the outlook for resin supply now and tomorrow?

Getting high-quality biotherapeutics to patients on time requires a concerted effort across suppliers, manufacturers, and regulators. Together we can create more reliable supply chain operations. Even though security of supply is mostly of importance in clinical and commercial manufacturing, it’s never too early to familiarize yourself with what to expect.

Learn about our approach to security of supply to help reduce supply chain risk, build resilience, minimize raw material variability

8. Does the resin meet quality standards and come with the necessary regulatory documentation?

When you’re working in a regulated environment, preparation of standard operating procedures (SOPs), quality control, and clinical and marketing applications to regulatory agencies are key. Look at what support you can get for the resins you plan to use in your processes to avoid lot-to-lot variability and other unpleasant surprises.

9. How sustainable are the resin and the supplier?

Our industry has to keep pace with the demand for life-saving therapeutics for a growing population. At the same time, climate change, biodiversity loss, and competition for resources require every sector to rethink its business.

Learn about how decisions in process development affect environmental sustainability:

10. Can the supplier help me with complex process challenges?

Whether it’s a result you didn’t expect or a mandate for increased process efficiency, you have a helping hand in finding the best path forward. Our tenured chromatography specialists and dedicated service teams are ready to assist you.

11. Want to test a Cytiva resin or get more guidance?

We can help you select a resin, develop your downstream process, or optimize your methods for your application.

Click on your molecule of interest to contact us:

Checklist: choosing a purification resin for your bioprocess