From peptides to mRNA therapies – and hybrid modalities such as antibody-oligonucleotide conjugates – modern biotherapeutics are pushing analytical science to its limits.

“We are dealing with molecules that refuse to reveal themselves to a single method or a single answer,” says Koen Sandra, CEO of RIC group. The most challenging of these molecules sometimes earn nicknames like “the monster” or “the beast.”

“Taming these crazy molecules analytically is the name of the game,” he says.

At ISC2026, Sandra will draw on nearly two decades at the forefront of biopharmaceutical analysis. Here, he previews his short course and keynote lecture – and reflects on how analytical science is evolving to keep pace with increasingly complex therapeutics.

 
Can you briefly introduce yourself and your role at RIC?

I’m a passionate analytical scientist who “accidentally” ended up being a CEO of an ambitious company. While I’m no longer at the bench or in front of the instruments, I genuinely enjoy interpreting data, discussing findings and sharing knowledge with team members, young scientists, clients and partners. And although I understand the need for supportive activities, operational flows and policies to allow our business to grow efficiently, when all is said and done, I'd personally rather be persuaded with solid spectra and interesting chromatograms.

What will you be covering in your short course and keynote at ISC2026, and why are these topics important now?

Biopharmaceuticals, biopharmaceuticals and biopharmaceuticals!                                  

The short course will cover chromatographic and mass spectrometric methods for analyzing nucleic acid and protein-based medicines. I have always found it rewarding to share our knowledge, whether it’s with someone who is getting introduced to the field for the very first time, an eager intern, a new RIC colleague, an innovative partner or customer. The discussions it triggers and the ideas it generates are so valuable. It is striking how the course material evolved over the years as analytical scientists sharpened the toolbox with novel reagents, innovations in column technology, low adsorption flow paths, ever more chromatographic dimensions, not to forget the many advancements witnessed in MS and the coupling of historically incompatible separation modes.

Furthermore, a decade ago, it was all about proteins – interest in nucleic acids was still marginal. Today, things are substantially different – and we may even discuss the analysis of antibody-oligonucleotide conjugates (AOCs) (cool stuff!). The keynote lecture will further build on the short course and will reflect on recent advances in one- and multidimensional LC-MS to study the structural and functional intricacies of biopharmaceuticals in great detail.

From a broad perspective, which markets are you currently focusing on, and what has driven this focus?

For nearly twenty years, we heavily focus on biopharmaceuticals, largely in response to industry demands. This direction wasn't part of a specific strategy, rather it developed organically. The challenges associated with unraveling the structural and functional intricacies of these ever more complex modalities demand specialized analytical skills, which we have steadily cultivated over time.

While recombinant proteins and monoclonal antibodies dominated our project portfolio for some time, today we are also investigating alternative antibody formats like antibody fragments, antibody-drug conjugates (ADCs), bispecifics, fusion proteins as well as peptides, oligonucleotides, and larger nucleic acids such as lipid nanoparticle (LNP) embedded mRNA or adeno-associated viral (AAV) vector encapsulated transgenes. To add further excitement, our lab studies a variety of combinations of the above, such as antibodies or their fragments conjugated to peptides, oligonucleotides, AAVs or LNPs. Some of our clients and some of our team members often refer to these complex modalities using nicknames such as "the monster" or "the beast." Taming these crazy molecules analytically is the name of the game, sometimes with a few bruises and scratches along the way.

How has the biopharmaceutical landscape changed over the past 10-20 years, particularly in terms of the molecules analytical scientists are now being asked to characterize?

I have had some interesting discussions with peers, including Lucie Nováková and Michal Holčapek, the chairpersons of ISC2026, on the definition of “biopharmaceuticals.” The term lacks a universal definition and is inconsistently and differentially used in regulatory, scientific or industrial contexts. Readers can nevertheless challenge me on this statement. Early definitions referred to biopharmaceuticals as products originating from living systems involving biotechnological methods like recombinant DNA technology. Undisputable examples include recombinant proteins and antibodies, transgene carrying viral vectors (AAVs) and CAR-T cells. Interestingly, in-vitro transcribed mRNA does not fit this description even though it relies on recombinantly produced plasmid DNA as an essential raw material. Equally so, chemically synthesized oligonucleotides (siRNA, ASO) and peptides do not fully adhere to this description. Analytical scientists, nevertheless, tend to consider all the above modalities biopharmaceuticals. This seems to be driven by their molecular nature (polymers of amino acids and nucleotides, regardless of the route of synthesis) and analytical challenges; if it is complex to study, let’s label it “biopharmaceutical.”

We are dealing with molecules that refuse to reveal themselves to a single method or a single answer. They are not defined by how they are made, but by the fact that without orthogonal, high‑resolution analytics, you simply do not know what you have. They demand depth, orthogonality and curiosity. So maybe we should no longer call them “biopharmaceuticals” but rather PATs (poly-analytics therapeutics). I’m certain my father would appreciate that.

More than ever, there is a need for speed and getting more insights with less material. This push for better and faster results creates a demand for new technologies. As innovators in the field, we are often involved in shaping these advancements. Recently, one of our colleagues completed an industrial PhD focused on the development of tools for antibody characterization. Together with the team, she designed a range of platforms based on affinity chromatography, multidimensional LC and native MS that were readily applied in customer projects. As an extension, and driven by industry demands, the team consolidated multiple assays into a single platform and designed “the ultimate antibody analyzer” embodying both structural and functional analysis. We are looking forward to sharing all the ins and outs at ISC in Prague.

Equally so, the appearance of mRNA vaccines has urged the development of novel methods to study various critical structural properties. Some of our scientists went totally crazy on these molecules and came up with an RNA mapping solution based on pre- and post-column digestion that reveals various hidden secrets of these study objects. I recall saying their idea would never work. I’m happy they proved me wrong!

What trends are you seeing in the outsourcing of analytical activities in drug development?

The (bio)pharmaceutical industry is increasingly outsourcing activities throughout its value chain. Virtual biopharma companies take this approach even further, running with minimal staff and externalizing almost all operations. Outsourcing gives companies access to expert knowledge and know-how – for example, in drug discovery, formulation and process development, manufacturing, analytics, regulatory filing, clinical trials, logistics, and so on – that are difficult, expensive and time consuming to build internally. These outsourcing firms have gained expertise from successfully – and less successfully – executing dozens of projects with a multitude of sponsors and are today, considered as strategic partners rather than simple vendors.

Specifically, concerning RIC, sponsors frequently describe us as an extension of their laboratory and an integral part of their team. This is a valued position that aligns with the partnerships we pursue. 

Where does RIC fit into the research and development pipeline for both startups and established companies?

As an R&D partner, we team up with various companies active in the biopharma space. Biotech companies typically reach out as they lack analytical knowledge, know-how and technology to characterize their molecules; big pharma might be on the lookout for niche expertise, extra capacity to develop methods or just flexibility; CDMOs having a bad day typically need help with root cause investigations for unexpected issues related to the product or irregularities observed during manufacturing; QC labs aim to identify the unknown peaks that suddenly pop-up or want methodological issues solved; tech companies ask us to challenge their newest solutions using the most complex and newest therapeutic modalities. Every now and then, we are confronted with high-priority SOS projects that cannot be solved in a snap. I personally call them our “fun” projects…

What is the broader value of analytical science in research and development today?

Overall, the impact of analytical sciences has dramatically expanded across various industries. In the past, it was mainly a tool to pass the symbolic quality control gate at the end of the line. Nowadays, it has become an inherent part of the entire drug development cycle, involved from the early start and moving along with the product. Today, analytical chemistry is not just a checkbox; it shapes decisions from day one. Analytical scientists are involved in drug discovery, formulation and process development, in-depth characterization and critical quality attribute (CQA) determination, development and validation of methods for stability studies, release testing and bioanalysis (PK/PD, ADA), not to forget researching biosimilars. In the latter case, a powerful analytical package demonstrating structural and functional similarity could reduce or eliminate the need for clinical studies.

The important role analytical sciences plays should never be overlooked. Despite the tremendous impact we have, analytical scientists are way too modest (at least the majority). As one of our customers nicely stated recently: “You have kept us out of trouble so often.” What a compliment.

Looking ahead, what trends do you expect to shape the future of analytical science?

Obviously, AI is lurking behind the corner and we are looking into its possible uses as we speak. It will undoubtedly help us manage and mine increasingly complex datasets, but interpretation, context and scientific intuition remain human tasks. That’s what makes our work so much more fun, right? Furthermore, sustainability (not just the next buzz word) cannot be ignored in analytical chemistry and will transform current practices. It's noteworthy that it is interconnected with AI: the latter promotes sustainability, but its operation demands substantial resources and energy. Automation and miniaturization further complete the story.

What do you personally find most rewarding about working in analytical science?

We have been blessed with an awesome ever-expanding team and a thriving business. I know it sounds a bit corny, but for me, it’s all about the science, not about the money (I have even scared our business partners with this statement). While revenue is obviously essential to keep our company healthy, to take good care of our team, and provide an awesome working environment along with top-notch science and tech, I most of all enjoy those eureka moments, their resulting impact, and the goosebumps and sparkling eyes that come with it.

There is nothing more rewarding than looking at chromatograms, spectra, or data like a true detective solving the most challenging questions – whether it’s discovering new biology, understanding the tiniest details of complex biopharmaceuticals, or tracing chemicals at levels once deemed impossible. It is even more rewarding if you can experience this as a team (the funny thing is that, while addressing this answer, a colleague enthusiastically ran into my office yelling “we have discovered a new protein variant”). The excitement peaks when a therapeutic or vaccine the team has researched gets approved and, after years of hard work, finally reaches patients.

The International Symposium on Chromatography (ISC2026) takes place in Prague, Czech Republic on September 6–10. To find out more, visit: https://isc2026.org/

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