Tailoring LC Solutions for Growing Biopharma Demand

Biopharmaceutical development is currently one of the fastest growing areas in the life sciences. With this comes an increasing need for analytical solutions able to cope with the challenges offered by biopharma samples. Compared to other sample types, the conditions required can be harsh due to factors such as salt content and pH that are unfriendly to the maintenance of most instrumentation. The nature of the molecules under analysis can also mean that surface interactions are potentially problematic. Therefore, there was a need to design a system capable of coping with these difficulties on a routine basis, that was more robust and did not compromise sample integrity or analysis precision. To address this, Agilent have launched the InfinityLab Bio LC portfolio, a liquid chromatography (LC) system designed to be completely biocompatible and bioinert.

We spoke to Dr. Tom van de Goor, associate vice president R&D, liquid phase separations business at Agilent Technologies, about the launch of the InfinityLab Bio LC portfolio and the impact this will have for users in the biopharma sector and also in other markets.

Karen Steward (KS): The release of the InfinityLab Bio LC fulfils a previously unmet need in biopharma analysis. What, though, do you think has driven the rapid growth in the biopharma sector compared to traditional pharmaceuticals?

Tom van de Goor (TvdG): That's a really good question. We've been seeing over the last years a big shift from small molecule pharma, or traditional pharma, to biopharma. I think it's driven by a number of reasons. First of all, I think most traditional pharma companies are shifting more to biopharma applications. In small molecule pharma, a lot of the drugs are coming off patent so there is a shift to generics there. Especially for pharma and biopharma companies, there will be much more business in the coming years driven by the advantages that biopharmaceuticals bring. They are much more patient-oriented and may bring less side effects. There’s an opportunity to deliver medicines that are tailored to treat individual disease states specifically in a very targeted way.

The other thing that is happening relates to the way pharmaceuticals and biopharmaceuticals are produced. Biopharmaceuticals are manufactured or generated in living organisms which is very different from most synthetic pharmaceuticals in the traditional pharma space. Therefore, the challenge of characterizing these and making sure that they meet all requirements and are safe is a very different one than we had before. Traditionally in pharma batch manufacturing, you would do an end state quality check and release the product. In biopharma, larger bioreactors are often run in continuous mode, so there is more need for a Quality by Design approach, continuously checking many conditions during the process. That requires many more measurements, and so I think those are some of the reasons why there is big demand for technology to perform this kind of measurement.

KS: Biological applications for LC offer some unique challenges due to the conditions required and nature of the biomolecules under analysis. Does maintaining a system such as this, designed specifically to cope with these biological issues, require any additional servicing or more regular checks than other systems?

TvdG: With regards to the difference between current systems and these future systems I don’t think it’s all black and white. Before dedicated bioinert or biocompatible systems were available, many customers were already doing analyses of biomolecules. At that time many people realized that some aspects of the methods they were using, like solvent concentration or extreme buffer conditions, could lead to corrosion because the systems were simply not inert enough to withstand those conditions for a long time. From the analytical aspect, there are some specific analyte interactions between the system itself, and things that may leach out of it over time, and analytes that you are analyzing where there are some specific needs too. Traditionally, people would have tried to passivate their stainless-steel systems in order to reduce the analyte interaction. That is a very tricky thing because you are treating the systems with pretty harsh solvents and that has led to the fact people have really been looking for something that is more robust for analyzing biomolecules.

Therefore, I think that, as we introduced these bioinert and biocompatible systems, the service and support aspect is actually going to go down because most of the customers that have been using these methods have been complaining that systems were not as robust as they would have liked. But with these new systems, the envelope is clearly expanded so now people can do these analyses without having to worry that their system will not be able to withstand it. So, my feeling is that we are increasing the playing field and will see a reduction in the need for service which will be a prime benefit for the users.

KS: The new systems have obviously been focused to expand and facilitate the growing biopharma field in particular. But can you tell us a bit about some of the other areas that have benefitted from the creation of this system too?

TvdG: They are of course optimized for biopharma because biopharma has a very challenging set of requirements, but it's not that these new systems are only for the analysis of biomolecules, definitely not. There are also other areas where people have had difficulties with systems. We're just opening up the usability or the areas where people can use it, without having to be concerned about these things. We expect that a number of customers will switch and take this as their new standard for most of the things they do. If you talk about analyte interaction, there are many examples of customers that have noticed that certain analytes in combination with certain materials may be problematic. For instance, a specification for system carryover. If you inject a certain sample into your system, carryover describes how much of it sticks to the system and therefore could disturb your next analysis as you may still measure something that you injected before. This is a very important topic which is why many manufacturers have specifications for carryover. Carryover specifications are always measured by testing certain tricky substances and everybody uses the same substances so that there can be comparison between different suppliers. But these standards are mostly not the compounds that people are measuring, and so you will always find certain analytes that are challenging because they are interacting with certain materials. What we have seen with these new systems that use more noble and more inert materials is that, generally, the number of compounds that show difficulty is greatly reduced. In addition, we offer several material versions for certain critical components. Here specifically, I would speak about injector needles because they are the components that have the most contact with the sample as it is being introduced. Here, we offer a range of different materials so that if there are still any specific interactions for specific compounds, there are still opportunities to improve. Not only by choosing a different material, but also, and this is standard in most of our systems, the ability to run wash procedures to eliminate this type of carryover.

I think another area where there is a lot of interest in these kinds of systems as well is where people are coupling LC, for instance, with inductively coupled plasma-mass spectrometry (ICP-MS), for elemental analysis of certain compounds. Here, any element or leaching that comes out of systems is very critical. We have seen in the past that bioinert systems are very popular there.

KS: Do these solutions help labs impacted by COVID-19 shutdowns and if so, how?

TvdG: There are of course many aspects to what COVID has done to all of us, not just our customers and ourselves. But I think there are many things that have enabled us to help our customers during these difficult times. This includes systems we already had in place like remote instrument diagnostics, easy repair options and a worldwide capability to help our customers. But in terms of this system, I think the more inertness we bring to the system the fewer questions will need to be escalated through the service organization, reducing the need for support. So, if we can reduce support needs or make instrument diagnoses remotely it will of course be very helpful.

We brought out an ebook on optimizing LC methods and method development in COVID times which includes a number of very interesting pointers to what customers can do and what Agilent offers.

KS: Are there any aspects of biopharma LC analysis that remain challenging that you hope to be able to address in the future?

TvdG: I think there are still many challenging questions to be answered. If you think broadly about biopharma and their challenges and needs, the molecules that they are creating are very complex. Therefore, a wide range of tools are needed to make sure that what has been produced is also what one wanted to produce, and I think it's not a single instrumental method or even a single platform that can handle all of that. Now LC, and LC-MS in particular, is very suited to that. A number of critical quality attributes, such as aggregation, charge variants, the peptide backbone composition and a number of other things can easily be measured using these tools. But there’s a big difference between making these measurements in a lab during development compared to production. During the development phase you check whether maybe the conditions in the bioreactor are optimized but in the end these things are being produced on a much larger scale in a manufacturing setting. There is therefore a need to move these measurements closer to the bioreactor. Our biocompatible version of the recently released 1290 Infinity II Prime Online LC system is designed to address this. It basically allows you to sample directly from the reactor or from the stream coming from the reactor rather than taking samples out of the reactor and analyzing them in the lab. Biotechnologists need to make sure that the reactor is stable. We expect this new product to bring another level of confidence that what is being produced is going to meet the requirements. We are really excited because if we can show that these systems are also robust and help to maintain the quality of the products that come out of these bioreactors, I think that would also be a big step forward for one of the big challenges that biopharma has.

Commenting on the InfinityLab Bio LC portfolio launch, van de Goor concluded, “We're really excited about this because it's a really big and broad launch. It lifts our entire portfolio to new capabilities and also opens up the opportunity to use these new modules in more complex workflow configurations. With that we hope to really start to address more challenges that the pharma industry has.”

Dr. Tom van de Goor was speaking to Dr. Karen Steward, Senior Science Writer for Technology Networks.