Interview with Ronald de Niet, general manager of Hycult Biotech bv In the role of your raging reporter, always on the spot 'where it's hot and happening', I regularly have pleasant conversations. Rarely, however, have my conversation partner and I been in stitches from the very first moment. With Ronald de Niet from Hycult Biotech bv this was the case after about 30 seconds. Funny man. But hey, antibodies stored in cancer cells, that sounds less funny, don't you think? Indeed, Hycult Biotech is involved in antibodies. For those who didn't pay attention in biology class: antibodies are proteins that the body produces when it detects substances – antigens – that do not belong there. Think of viruses and bacteria. The antibodies that Hycult Biotech produces find their way to customers in the medical sector, including pharmaceutical companies, university hospitals and bioresearch centers. To be precise: to the laboratories there that use them for research purposes. Not for clinical and therapeutic applications. At least, not yet. Research Use Only. 'That's quite a specialist business', I hear you think. 'You probably have to be something of a pharmacist, biologist or researcher yourself to be able to run a company like that.' Well, not necessarily. As a civil engineering engineer, you're doing just fine, aren't you, Ronald? "Pretty." Because at some point you thought: get rid of that water, I'm going to use the antibodies? “Actually yes. Look, it's like this: Hycult Biotech was once founded by my father - after a long and turbulent run-up. After graduating, I tried it for a year, but to be honest I couldn't really get into it. I wanted to do my own thing. So I chose a career in civil engineering. Only to return there some twenty years later, when my interest had considerably aroused. In the meantime, I have taken over from my father and can call myself general manager.” A long turbulent period? “Yes, they could write a soap opera around that. I will spare you the details, but if I say: home furnisher, furniture salesman, manager of a small veterinary medicine company, bankruptcy, director of a tissue culture products company, founder of Sanbio, the first in the Benelux specialized in antibodies, then you have a I have some idea of the paths and abysses my father went through before he had Hycult Biotech.” And that's what it does now: standing? “Like a house. We produce and supply antibodies to the medical sector worldwide and we are achieving growth. Slow growth, yes, but that has a lot to do with the niche market we are in. Perhaps I should explain it to you. In the medical field in which our customers operate, two types of defense against pathogens are basically distinguished: acquired, adaptive, and innate, innate, immunity. We are mainly active in the latter area and are known as an authority. A specialist who distinguishes himself based on quality and service. Even though competition has increased considerably in recent years, innate immunology is still a very interesting market for us.” The antibodies you produce are for Research Use Only, right? "Precisely. To give you an insight into those products and processes, and therefore into our business model: new, specific antibodies are constantly being discovered. We are constantly at the forefront of these developments and we always weigh the risks and opportunities: do we participate or do we not participate. There are all kinds of factors involved. For example, whether the antibody can be reproduced at all. What kind of agreements can be made with the researcher or university. And of course whether the commercial prospects are favorable. It is obvious that it is inevitable that we sometimes invest in a dead end. On the other hand, it also happens that an antibody suddenly starts running after four years on the shelf. It's all in the game. Antibodies are the most important, but not the only, products we supply. We also market ELISA kits.” Oh yeah? How fun for the children, dolls! "What…?" Eliza Doolittle, My Fair Lady…? “Um, no… ELISA stands for Enzyme-Linked ImmunoSorbent Assay. Which means a method by which proteins can be detected. ELISA kits are essentially in vitro diagnostic tests that can identify the type of inflammation that activates antibodies outside the body – hence in vitro. The research kits that we market are ISO9001 certified. In recent years we have also certified for ISO13485. This also allows us to develop, produce and sell ELISA kits to the diagnostic market. So top of the bill.” New products, new opportunities? “Yes, developing, producing and marketing ELISA kits in accordance with ISO13485 offers us more than just a business opportunity. It teaches us a lot about the aspect of quality, the backbone of our organization. In that sense, it was a good decision to venture down this path. So as far as opportunities are concerned, they certainly exist when it comes to ELISA kits. The market is bigger than the competition, so to speak. We are also considering making ourselves available to pharmaceutical and biotech companies for contract manufacturing and contract development, among other things. We are so well equipped and experienced that we also see opportunities in that area. As a supplementary activity, of course.” Speaking of the competition, you are at the forefront and are therefore being watched. Not afraid of plagiarism? "No not really. In principle it could be possible, but in view of costs and complexity it is not likely. And when it does happen – usually somewhere in the Far East – the quality is usually so disappointing that it can hardly be called a threat. At least, so far that has not been the case.” Ah, abroad, let's talk about that. You deliver worldwide, but you have no branches outside the Netherlands. How do you keep in touch with the local markets? “Well, it won't be because of our network. We maintain contacts with researchers all over the world, with whom we continuously exchange insights regarding knowledge and quality. We also regularly participate in 'grants'. These are international funds that are awarded by organizations, institutions and governments to research projects in which multiple parties, such as universities and companies, collaborate. This way we keep our finger on the pulse. But of course also through conferences, fairs and our distributors. We have two of these that are directly affiliated with us, one in Germany and one in the USA, both of which are among our most important market areas. In addition, we are represented by external agencies in the rest of the world.” I think you really operate at the intersection of technology and commerce. I think that requires a special type of employee. "Beats. Our preference is centipedes. To technical people, from MLOs to PhDs, if possible with a commercial slant. They're not easy to find, I can tell you. Not that we constantly have vacancies, fortunately our people stay with us for quite a long time, but perhaps I will make contacts through FHI who can play a role in this.” But I guess technology prevails. “In the end, yes. Like I said, quality is our backbone. Growing, checking, testing, multiplying and preserving antibodies and developing and producing ELISA kits is an extremely specific biotechnological matter that requires particular care.” I understand that. What should I imagine? “The following: the mother cells are stored in special containers where they are kept under icy conditions. Mind you, this concerns very delicate, living material that, after it has thawed, we cultivate it with the necessary attention and must keep it in optimal condition for as long as necessary until sufficient, high-quality antibodies have been produced. After a number of steps, such as filtering and purification, the semi-finished product undergoes a reprocessing process, which makes it longer shelf-life and treatable. So that is what we ultimately supply: the antibodies. We store these, use them for the development and production of ELISA kits or forward them to our clients. It is almost impossible to see with the naked eye. It's just a tiny bit of powder or a few hundred microliters of liquid in a very small capsule. That is it." And those containers, how do they work? “These are highly insulated storage tanks of about sixty centimeters high with liquid nitrogen, in which the cells are stored at approximately -190ºC. What you may be interested in knowing: the cells in which we store the antibodies have fused with cancer cells. This fused cell is also called a hybridoma. A cancer cell usually remains alive much longer and is more reproducible. Normal cells die sooner.” Ew…scary! "Scary? Do you ever watch The Walking Dead?” Um, yeah… “That's scary! By the way, it is also about antibodies. But different."

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