Episode 2 – Ruminations on fermentation tech transfer with Oleg Werbitzky

Oct 11, 2021

About this Episode

We discuss industrial biotech tech transfer, from bench to scale, experiences at the interface of research and the private sector and the opportunities for industrial biotech in the circular economy.

Transcript

CB: Hello everyone, and welcome to Tech Transfer Talk. My name is Cameron Begley, and joining me today is a long-standing colleague of mine, Oleg Werbitzky, who lives in the valley in Switzerland. Oleg. Hello.

OW: Hello, Cameron. Hello. And thank you very much for having me here, for inviting me to discuss this exciting subject with you.

CB: Uh, my pleasure, Oleg. And our shared history goes back to your time at Lonza and my time at CSIRO. So, we’ve had a good, a good decade experiencing the ups and downs of technology transfer through our journeys. But perhaps, Oleg, you could say a little bit about yourself, just to allow the listeners to get a sense of your background?

OW: Yes, absolutely, Cameron. So, my name is Oleg. I’m actually from Germany, and I would say I’m an industrial scientist by profession. I have a training as an organic chemist, actually a doctorate in organic chemistry from Technical University of Munich (TUM). And in the early 90s, I decided to trade my academic potential academic career for an industrial career. So started in the research department of Lonza, which maybe some of you might know. This is one of the leading life science companies globally, strongly involved in chemical and biotech manufacturing for different industries, for the pharmaceutical industry, for the agrochemical industry, for the nutritional industry. I had a quite long journey with Lonza, more than 20 years, starting as a research chemist and building a business in the field of large synthetic molecules, namely peptides and oligonucleotides. And then later, when I met Cameron, I was in charge of establishing a corporate, internal corporate venture program covering all the different fields of Lonza, together with another colleague initially. And then obviously we have been joined by other people as well. And so, this brought me into innovation and open innovation, and also in the concepts of technology transfer, in the primary sense we are going to discuss today.

CB: And our recent activities have been with you in your , in NC Health Sciences and, and your own private activities since, since JTI. Yeah?

OW: This is correct, yes. Actually since 2015, I’m, I’m actively undertaking a certain number of, of projects in the innovation space. And some of, some of them are related to consulting activities, helping other people to take advantage of my experience specifically related to technology transfer. So, principle, that’s probably the reason Cameron invited me today.

CB: Well, it is Oleg. And, you know, have your experience at Lonza where you built the peptide and oligonucleotide business., puts you I think in a unique position about how technology transfer works from, from the bench to production scale. But as, as we were talking leading up to our discussion today, you have a bit of a different definition of technology transfer from your industrial days. I think it’s really interesting what you, what you immediately associate with that phrase.

OW: Yes, absolutely. Because in an industrial manufacturing context, we speak about technology transfer when we mean transferring from the laboratory into the pilot scale plants, or from the pilot scale plants and to the commercial plants, or from one commercial plant to another plant. So, which is, it’s also called technology transfer, but it’s actually more process transfer. And during my days and peptides actually this was the starting point because when, when we entered the peptide space, we actually started with a technology transfer from, from a, from another industrial group which used to produce quite a complex molecule, probably the most complex things you could do in synthetic peptide chemistry at this point in time. And our role was really to scale this up by a very significant factor. This was the starting point. And then a few years later when we started developing the entire business, we obviously had to look deeper into the specific technologies which are at, at the basis of, of, of making such things like, very complicated chemical molecules and purification of these products. And this was then the other side of the technology transfer, meaning we went out into the academic world in order to learn and transfer the most advanced techniques and technologies available on the market into our manufacturing context.

CB: It’s quite interesting, Oleg, that, that in some respects there’s two types of technology transfer going on in this conversation. One is, for all intents and purposes, an almost, an almost fully developed process technology, which is, which is a matter of scale up and that’s  you know, that’s the world you lived in and described. Yet the world that I generally occupy and think we work on very much together these days in our projects is where we’re taking, you know, very underdeveloped technology things, things that are really, you know, at early stage demonstration or even just past proof of concept and, and the technology transfer journey for these things, starting at a much lower technology readiness level is, is a different proposition in so many ways compared to a process transfer.

OW: Yes, absolutely. And I think the ,obviously the, the type of, of hurdle issues and maybe other, other problems you’re facing in these two different types of technology transfer also quite different. For the industrial technology transfer, you’re primarily in a framework which is which is defined by equipment, by scale up issues, by the specifics of the place from which you transfer and the specifics of the place you transfer into. Whereas for the, for the other technology transfer from an academic maybe environment into an industrial environment, you have a number of additional aspects which come into play which are also very, very interesting to be discussed. In addition to purely technical aspects, we start having additional aspects which are on a cultural difference which you have typically between these two communities.

CB: Yeah.

OW: They are primary interests and also their primary mandates because, you know, people who are paid by public money and actually are competing in a global academic environment have a different perspective of the world than, let’s say, industrial people who primarily want to successfully scale up and then really look into obviously, safety is always the most important factor, but the economy comes soon afterwards, meaning making a maximum out of the reactor capacity you have available in terms of commercial outcome. And this is the primary, the primary objective.

CB: I’m interested in the culture question you raised there Oleg. And, you know, you obviously, from your time at TUM and then moving across to Lonza, but what are your what are your insights or your experiences on managing this cultural difference? Um, from, from your time at Lonza and perhaps even JTI, you know, we sat to some extent on opposite sides of the table for a period. I’m interested about your experiences on managing that cultural divide.

OW: Yeah. Well, I think we need to look at this as something which is a very general industry trend. I mean, now the open innovation as such, I think this is actually resulting from the understanding that we have a strongly diverging universe of technologies in general. And this was understood by the industry already, I don’t know, a couple of decades ago, probably 25 years ago, when we had the technology revolutions in the IT space and also at the same time in the biotech space, and many of the multinationals understood that they will not be able to continue to support the growth. of their business growth with their own R&D capabilities. And also, they understood that there is the possibility to leverage public money in a certain way by de-risking the project in handing over certain parts of the innovation value chain to the academic world. And obviously, overall, this is a positive, I think, concept. And we know companies which pioneered these things like P&G was their connect and develop concept, which in principle, I think up to 50% of their innovation is coming from, from, from this type of concept. So, there is quite a history in how to handle these things and how to manage these things.

And now obviously we the chemical industry is a relatively conservative industry and much more conservative than the IT industry. So, they are not always the pioneers in these kinds of things. But we had the advantage of being able to take some of the learnings the other people have established. This entire process is still not fully resolved because many, many of the issues are still quite relevant. And just maybe to try to, to name a few of the main difficulties. From my personal experience, for example, I think there are a number of gaps on both sides. Yeah, obviously the gaps on the industrial side is the specific knowledge which the industrial partner is looking for. That’s the reason they are ready to pay the money to the other guy. So yeah, but also on the academic side, there are certain limitations. And I think the first one is probably, a poor understanding of, of the market and the commercial aspects of the issue. So, it’s difficult. It’s not their role and it’s difficult for them to understand, the relevance of certain factors on the commercial side. And sometimes it seems that we need the role of an innovation manager is actually to be the translator between these two worlds, in order to sufficiently, efficiently exchange the information and be able to bring the two worlds into a same set of coordinates, you know.

CB: Yeah, very much.

OW: I think to continue maybe. was the gaps. There is certainly a different understanding of the importance and the quality of the IP protection.

CB: Yeah.

OW: And quite often nowadays I think everybody in university understands that patents are important. But they don’t really understand what is important in a patent. It’s not only to have a patent application, a number, and maybe a file which is going through prosecution. It’s really to have a, granted patents with a strong set of granted claims, isn’t it? And this is this is a big difference. So, this makes the value of a certain, of a certain technology.

CB: Yeah, for sure. I think it’s the IP issue, and the management of that, I think is becoming more widely known in the academic community. So, I think that’s a very accurate point. I’m interested about that role of the innovation manager or innovation broker, both of us have played that role at various times on the journey. There’s an interesting discussion in Australia that is starting at the moment, Oleg, which you may or may not be aware of, about the need to actually properly develop innovation management, commercialisation skills, in contrast to, you know, pure science or applied science skills. You know, there’s a bit of an assumption in some parts of the innovation system that I’ve seen Oleg, that scientists are completely able to do their own business development. And the role of the business development manager or innovation broker is, perhaps less important than it might have been ten, fifteen years ago. When this, you know, this activity of technology transfer really started to gather momentum. What do you make of some of some of those assumptions?

OW: Uh, well, I probably would disagree with this, with this analysis. And the reason is that, we understand that nowadays, in a world where more and more we are doing things which are not our primary focus, you know, we are typing in documents, we’re scanning everything. we are doing a lot of technical work. I think here we are speaking about something which is quite complex, and it could be an advantage, in my view, it is an advantage really to focus on the specifics. Meaning a good scientist, if he wants to be a good scientist, he doesn’t have to play the role of the business development person because this requires a different skill set. And I’m not saying a scientist cannot be a good business development … but this is a life decision. You know, this is like when I decided to be an industrial scientist rather than being an academic scientist. This was a decision. Now, I’m probably not the best person to train students or to give lectures or to invent maybe certain type of very advanced technologies. I’m a specialist in translating technologies into something which is scalable and commercially be, commercially competitive. And similarly, if you want to be successful, I think it’s important to have a combination of skill set in your team instead of having everybody is doing everything, you know.

CB: Yeah, yeah, it’s a range of skills that are required. So, it sort of comes back to that conversation that’s happening here around should, should there be some degree of specialisation in these innovation management and commercialisation skills. Should, should this be a, a better-defined career path rather than something that, that, that people almost stumble into at times?

OW: Yes, I think this is. This makes sense. Every university has a tech transfer office, but the quality can be very different, and the roles can be very different. And partly we are back to the typical problem that you know, how are the people in these functions. What is the situation, you know, of these people? And is there really enough motivation to be commercially successful?

CB: Yeah, yeah. And it comes back to that point you mentioned earlier around cultural alignment.

OW: Exactly. And the thing is that when we live in a world which is dominated by economic perspectives, people who are in these functions quite often have to be between the academics who have different priorities from the very beginning of the role. But also, then there are there are additional things, because nowadays, as we know, science is expensive, and typically people have to get third party money in order to finance their research. So, this brings us back to the need to, to publish their work, to present the work, to show a strong presence in the academic world, which in principle has a conflict with the IP topic we just discussed a couple of minutes ago. Think this and this is the problem. And ultimately, it’s the problem of, in a certain way, of the ownership of the ownership. Because what is more, who is the owner who decides about a strategy of a certain technology? Is it the tech transfer responsible? Is it the leading academic scientist who is behind everything? And how does this work? And then to complicate things even more, at some point in time, external people like ourselves come into play and start looking at the commercial side of things, and have a different perspective of priorities.

CB: Yeah, indeed. Yeah. And the possibility exists that neither the inventor nor the tech transfer office is running that. In fact, it could be the investor. It could be the private company that has made, made an investment in this particular piece of work or, some, some other interested party that that has the interest. So, another complication.

OW: Yes.

CB: So, I’m interested to bounce off the challenges and talk a little bit about some of the good things you’ve seen. Where have you found success in this tech transfer space that you’ve been occupying. Perhaps even happiness, Oleg. But let’s just go with success.

OW: Yeah. Well, I think it’s very important to mention here for, if we look at this. This topic from the perspective of the. Of the Technology Innovation Management Officer. Now if the. I think what is really important is to try to work with partners who are not very bureaucratic, who are, and we come back a little bit to the, to the prior question, which means who sufficiently well understand the context and the priorities of the industry. And I think there are, there are huge differences between different organizations globally, because I think I have worked with well, it was people in the US, obviously in Europe, in Asia, and also in Australia. So, we can say globally, maybe Africa being the only continent where we didn’t have any projects. But just to say that it’s not a matter of geography, it’s really a matter of culture. And the way a certain group responsible within, for example, the academic side, has succeeded in establishing a favorable context to work with. This starts already with simple things like non-disclosure agreements. You know, if it takes you two months to, to sign a non-disclosure agreement and, and then we can imagine how long it will take you to sign a collaboration agreement or a licensing agreement, all of that. And sometimes, you know, the people on the academic side, the tech transfer office people, they don’t understand the importance and the relevance of timing…

CB: Interesting.

OW: And thus, on industrial context is extremely important. And so, people who have very well-established processes and very clear rules are easier to work with. I don’t want to maybe name good or bad examples here, but just to say there are differences. And I think coming back to your previous question, how important is it to have people who are trained and prepared for these kind of roles? And this is an additional argument supporting the need to learn from others and to develop best in class practices for this specific role, because you can increase the value of your proposition to the industry by having clear rules which are acceptable for the industrial partner, because it’s always a choice, you know, that there is on the industry side. I’m not saying the industry is always right, and we are going probably to come back to this topic as well. But saying that when the industry is selecting projects, the ability to work with somebody is also a criterion. It’s not only about the absolute value of the science behind the technology. If you have a partner you cannot work with, then obviously this is reducing the value of the overall proposition.

CB: Yeah. So, the science or the technology in my experience is a necessary but insufficient condition for success. I think that if the science is good, that’s a great start. But these other aspects that you’ve been talking about, Oleg, are the things that make the deals go forward, make the partnerships go forward. Terrific, terrific science, but poor processes for external engagement are less likely to succeed, in my experience.

OW: Yes, I agree, I agree. And this brings us back to, to your previous question saying we need people who know how to do this. This is a part of the overall proposition.

CB: Yeah. So, from an industrial biotech perspective, just to focus a little bit on, on an area that we’ve, we’ve spent some time in, what do you think, you know, what are the opportunities look like for industrial biotech right now? There’s lots of talk around, you know, phrases, synthetic biology. and precision fermentation – one of one of my personal favorites, Oleg, which we’ve talked about before, so there seems to be a lot of talk about it. What are the opportunities in, in tech transfer and perhaps more broadly in this world of industrial biotech?

OW: So, my personal view on this is that, if we look at the biotech industry, obviously we know that this is typically segmented according to this color codes, which means there is the red biotech, which is everything related to farm and health. Then there is the worldwide biotech, which is probably the best to describe industrial biotechnology. And then there are the green biotech. These are biotech applications for agro. There is the blue one, which is marine applications. And if we look at all of that, it seems that the field is very strongly dominated since its start in probably the beginning of the 80s.The bio, the red biotech, and the reasons for that is obviously the huge potential and the very high margins in the pharma industry. And I think the total it’s a very important industry sector in general, biotechnology. But, it, it has not fully translated in some of the other parts up to now. And I would say white biotechnology is something which I personally would predict, a very strong potential. Am I not the only one? As we can see from, from different publications by different experts and consulting group leading consulting groups and also by where the investment money goes into. So white biotech, if this equals industrial biotechnology, this is something which has a lot of, a lot of potential. Why it is lagging behind a little bit is partly due to, to the differences in, in many aspects, for example, in the regulatory framework where essentially pharma being the dominating side of things, significantly restricted the, let’s say, the development of the toolboxes for a very long time. I’m speaking, for example, of the importance of certain microorganisms, where pharma needs to work with, or prefers to work with, microorganisms, which are considered to be, Generally Regarded As Safe, which quite often is called GRAS, and which means that all the toolbox has been developed around a limited number of microorganisms, whereas we have many more of microorganisms which are potentially relevant for the wide biotechnology, we simply don’t have the equivalent toolbox in terms of biotechnology, of molecular biology instruments, for example.

And then there is also the market side of things where we understand that from the perspective of, the sustainability of our planet in general. We need to move away from concepts where how we handle actually our waste streams in general and in more particular, now I’m speaking of the polymer industry and the problem of plastics, microplastics and the ocean and all of that, where due simply to the growing number of population and also the growing economic growth in general, this is starting to really become unsustainable and meaning we need to switch more and more to integrated system with cyclic, maybe concepts of economy.

CB: You know, this circular economy.

OW: Yes. And I think here is a huge potential for biotechnology because biotechnology typically produces products which should degrade in nature. And by this obviously reducing our waste problem in the future. And so, this is one of the of the driving forces behind all of that. There are obviously other also driving forces which come more from the performance side of things where we come to certain limits with regards what can be done with conventional, maybe purely chemical concepts, at least at commercially competitive conditions. And where it’s investing more efforts into biotech would certainly allow to produce things which are not available today.

CB: So one of the underpinning challenges then is around the diversity of developed organisms, developed fermentation platforms with all the molecular biology done so that we actually have more flexibility in the organisms we use and by extension, the molecules we can economically produce.

OW: Well, this is, this is one of, one of the aspects obviously. An entire process from start to the end goes beyond purely the strain itself.

CB: Yes.

OW: You also have obviously the fermentation process itself. You need to fit the existing capabilities, which for a certain number of reasons actually are quite diverse. We have a lot of possibilities globally. And then there is obviously the downstream processing side, the isolation part of the process, which also has to be in place. So, all these things have to play together. But ultimately there is always a bottleneck in a certain part of the process. And for moving really into wide, wide biotech, there are, there are a number of things which have been challenging, obviously beyond the cost aspect, the scale up aspect. It was the also what you just said regarding the organism, the expression system itself. And I think nowadays, as we have more and more tools available, considering the genome editing possibilities, which now become also more and more available, we will be able to generate better organisms.

But just I wanted to say that the other parts we should keep in mind, because once we will solve or resolve one bottleneck, we will have additional ones which could come up. It’s not like only one solution. It’s a more complex story. But what we see is actually globally, there a large number of projects now tackling different parts of the market which can be, which can be actually addressed with wide biotechnology. And this covers, if we look at this from a chemical perspective, this covers the entire field from small molecules where due to concepts like synthetic biology, in principle, we could imagine having one step processes making very complex molecules in a very specific way or to other type of products, which are maybe large synthetic molecules like what we discussed earlier, peptides or oligonucleotides, where again, with certain progress, which has happened on the technology side, now things become possible to be competitive with chemical synthesis.

CB: Yeah.

OW: And ultimately on the large molecule side was the ability to make, to design and make new types of proteins.

CB: Yeah.

OW: It was very specific tailored properties required for a certain type of application. So, we will be able to design solutions to optimally resolve a certain problem.

CB: Yeah. And it’s interesting you mentioned the proteins, Oleg, because when we, when we spoke with Maurice Maloney in an earlier podcast, what’s really interesting is, of course, that conversations around protein for food, whereas, and the alt protein space which I’m sure you’re aware of from an agriculture perspective, but here you’re I think you’re pointing more towards protein as a material and industrial product, which can be adapted and modified for industrial purposes in contrast to digestive purposes.

OW: Today, when we design proteins, we can integrate biologic functionality into that and meaning that we can take advantage not only of the material properties of something, but also integrate and create biologic properties into it. And this goes then beyond the pure material application, because this brings us back to, in some way to, to red biotech without being red biotech; white biotech for red biotech if you want.

CB: Yeah. Well, that concept, Oleg really services potentially, red and green and blue. It’s a broader it’s a broader concept of its white biotech from a production perspective perhaps, but it’s other sorts of biotech from a market perspective.

OW: Absolutely. And I think we, you know, now looking at what we all have experienced over the last, I don’t know, fifteen months or so was the pandemic actually this, this showed us a number of interesting examples at the interface of that starting, starting with, for example, all the reagents which are needed in order to, to have the PCR tests running, you know, which were not supposed to be needed at this scale, or all the components which, which are needed to, to develop or to run these tests that these numbers needed to scale up brings us back to tech transfer and all of that. What is also probably quite relevant is to consider what can be done in terms of biotech solution for better manufacturing in general. So, this starts with synthetic biology in general. How can we efficiently come up with new systems and also at reasonable costs, you know, because nowadays and some people describe it like CapEx is, the organism is now our CapEx. So how can we produce the required organism to make something with the lowest possible CapEx? And this, this is true for types of chemistry which we would like to replace, which are producing very, a lot of waste or which use harmful chemicals, or which need very harsh conditions. So, focusing on this and looking for biotech solution in this space.

CB: Oh, excellent. Excellent thoughts. Oleg, it’s been really fascinating talking with you today around your experiences in, in trch transfer and your reflections, you know, around industrial biotech and how it’s becoming more integrated into everythingthat that affects us from medical biotech through to other areas and other applications. So, Oleg, we really appreciate you joining us, and thanks very much for your time.

OW: Thank you, Cameron.

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