When drug safety fails, patients—and entire markets—pay the price. Understanding your CMC isn’t just compliance; it’s the line between therapeutic promise and product recall.
That’s the lived experience of Ron Najafi, a serial biotech entrepreneur whose forensic work on nitrosamine contamination (most notably in ranitidine/Zantac) made national headlines—and changed FDA policy. From bench chemist to founder of NovaBay Pharmaceuticals and Emery Pharma, Ron exemplifies the scientist’s role in both discovery and diligence.
We were contacted by a pharmacy out of Connecticut, and they were testing Zantac, which is ranitidine, the active ingredient. And they were testing it by gas chromatography. In gas chromatography, you are heating the sample significantly in order to volatilize certain impurities. And they were observing lots and lots of nitrosamines, specifically N-nitrosodimethylamine, NDMA—millions of nanograms of nitrosamine, which is just completely unacceptable.
NDMA, according to the FDA, you can have only 96 nanograms per day. Our investigation effectively unraveled what was happening with ranitidine. Effectively, ranitidine was breaking down, and the breakdown product of ranitidine was NDMA.
David Brühlmann [00:01:01]:
What does it take to build a company around a scientific discovery that reshapes public health policy? Ron Najafi has done exactly that. From his early days as a bench chemist to founding NovaBay Pharmaceuticals and taking it public to leading Emery Pharma, a CRO deeply committed to science, CMC and bioanalytical testing. Ron's career is a masterclass in turning scientific curiosity into real world impact. Today, he shares where that journey began.
Welcome, Ron. It's good to have you on today.
Ron Najafi [00:02:54]:
Thank you, David. It's a pleasure to be talking to you again.
David Brühlmann [00:02:59]:
Ron, share something that you believe about bioprocess development that most people disagree with.
Ron Najafi [00:03:07]:
I think one of the things that people should not disagree with is the need to do proper homework on CMC development, because that's going to be one of the biggest holdups as a project moves from pre-preclinical to preclinical and so forth. Understanding CMC, understanding the challenges associated with manufacturing, and the analytical chemistry of your drug substance and drug product—whether small molecules or biologics—are essential to your success.
It is also essential to your pharmacology and your toxicology. So you need to know as much as possible about your Chemistry, Manufacturing, and Controls. And I say that with some intentionality. Chemistry is really how you make your product—how you make your compound, how you produce your biologics. You really need to understand it well.
It makes a big difference in how you're ultimately going to manufacture the product—chemistry, manufacturing, and manufacturability—whether this is going to cost you a million dollars to make or whether you'll never be able to make it at all. So those are all connected and related.
And then, of course, Controls really refers to quality control. It refers to how you're going to test the product, how you're going to maintain it, and how you establish its shelf life.
So these are areas where there may be agreement and disagreement, but I think there should be more attention given to all of that—the CMC—at the pre-preclinical and preclinical stages, because the FDA cares about it, the EMA cares about it, and we need to make sure that we also care about these aspects. Otherwise, they can become a major holdup for anyone developing either small molecules or biologics.
David Brühlmann [00:05:19]:
Very good reminder. Thank you, Ron. And this is a point I've been stressing multiple times here on the podcast. CMC is important and should not be an afterthought.
Ron, you have been on a fascinating journey for several decades. Draw us into your story—what first sparked your passion for science, and what were some of the interesting pit stops along the way?
Ron Najafi [00:05:46]:
I’ve actually thought about it. One of the things that sparked my passion was when I was in high school and had a chemistry teacher who was very engaged in the subject. When the time came to go into the laboratory and perform experiments, we were given a lab coat.
I remember vividly carrying that lab coat—it felt like a cape, like Superman’s cape. It gave me a sense of authority and identity that I had never experienced before. That was one spark.
The second spark was when I was at the University of San Francisco, where I met the professor who later became my primary mentor during my bachelor’s and master’s studies. He strongly encouraged me to pursue synthetic chemistry.
I remember staying in the lab until 4 a.m. at times, working on reactions such as 9-BBN and other synthetic chemistry projects. Organoboron chemistry was particularly exciting—especially following the Nobel Prize awarded to H. C. Brown in 1979.
Another pivotal moment was when I was given a key to the lab. That was a major milestone. I felt like I now had my own lab space, my own desk.
So those two points were two sparks in my life. It was like a quantum leap from one place from one location to the next location. And it was transformative to most people that maybe not that big of a deal, but to me, getting a lab coat in high school and going to the lab at the University of San Francisco, getting a key to the lab and having my own desk in the lab was very significant for me.
David Brühlmann [00:07:45]:
And what were some other interesting stops and experiences you had along your—I believe it's more than three decades already now—as an entrepreneur and scientist? Tell us your story.
Ron Najafi [00:07:59]:
I have to warn your listeners that time flies. Three decades flew by so fast. But I never watched the clock, David. I have never been a clock watcher. I work, work, work—and I enjoyed it.
So basically, one thing led to another. I got my bachelor's and master's degrees with this professor at USF and ended up going to UC Davis, continuing in organoboron chemistry, which was the Nobel Prize–recognized chemistry developed by H. C. Brown. So I worked with several professors connected to H. C. Brown’s work, and I got my Ph.D. from UC Davis shortly thereafter.
I was really hoping to get a job in the San Francisco Bay Area, where my family lived, but unfortunately there were no jobs. Genentech wasn’t really doing synthetic chemistry at the time. There was Dow Chemical, Clorox, and a few other very small biotech companies—but nothing like what exists in the Bay Area today. Absolutely nothing. This was more than 30 years ago.
I applied to Hewlett-Packard in Corvallis, Oregon, but I was rejected. My mentor, George Zweifel, said, “Ron, if you want to go work for Aldrich Chemical Company, I can get you an interview.” I said okay. It was in Wisconsin, and I initially thought, “No, I don’t want to go to Wisconsin.” But I ended up going.
I interviewed in July—it was beautiful, warm, and sunny—and they made me an offer on the spot. My job started in February, and it was a blizzard with heavy snow.
I spent about two and a half years at Aldrich Chemical Company, where I worked on organosilicon and organoboron chemistry. Then I was recruited to join Rhône-Poulenc Rorer (RPR) in Philadelphia. There, I continued practicing synthetic chemistry—making molecules day in and day out—as a research scientist. I stayed there for another two and a half years.
One of the things I’m very proud of is that I started a symposium called Visions in Chemistry, which continued all the way up to the pandemic. Each symposium focused on a specific area of chemistry. The first one I organized was dedicated entirely to organoboron chemistry. I invited H. C. Brown, along with leading professors and scientists in the field, including my former colleagues from Aldrich.
After that, I really wanted to come back to California. The same recruiter who placed me at RPR introduced me to two opportunities—one in San Diego and one in the San Francisco Bay Area. I chose the Bay Area and joined Applied Biosystems, an instrument company focused on DNA synthesis.
There, I became deeply involved in phosphoramidite chemistry and got heavily engaged in Chemistry, Manufacturing, and Controls (CMC). There was a major issue affecting DNA synthesis—specifically, the phosphoramidites used for A, G, T, and C were not producing high-quality primers.
I dove deeply into the analytical chemistry behind the problem, identified the root cause, and resolved it both at small scale and large scale. For that work, I was awarded the highest chemistry award at Applied Biosystems among approximately 1,200 Ph.D. scientists.
That same year, I also invented a product called the Eco Funnel. It is a funnel that screws onto the top of a bottle to prevent hazardous vapor release and environmental contamination in the lab. I invented it to reduce pollution from laboratory operations.
Throughout my career, I’ve been actively involved in safety committees at every company I’ve worked for. I’ve always cared deeply about the environment. I cared about people. I didn’t want individuals to be exposed to chemicals unnecessarily, and I also didn’t want solvents evaporating into the fume hood. You know, you put a gallon of solvent into a fume hood and leave it open—within a few days, there’s no liquid left. Everything has evaporated. So I essentially created a trap to prevent evaporation. At the same time, you could safely dispose of liquid waste into the same container.
So I invented that product. Applied Biosystems was very forward-looking and an early adopter of new technologies. They supported the idea and told me, “Ron, go ahead—develop it, manufacture it, and patent it yourself.”
I developed it largely during my breaks—lunch hours, evenings, and weekends. The company chose not to pursue the patent, so I did it independently. I patented the product and built a company around it—CP Lab Safety, a laboratory safety–focused company. This year, we’re celebrating 30 years of CP Lab Safety.
I ran that company for several years and made sure it became successful. It was a challenging product at first. People would say, “Why should I buy this? Right now, I’m evaporating hazardous solvents in the fume hood for free. If I buy your product, I have to pay for it and also pay for proper waste disposal.” And I would say, “Yes—that’s exactly the point. That’s the responsible thing to do.”
If you evaporate solvents into a fume hood, it’s essentially like dumping them onto the sidewalk. If you dump chemicals on the sidewalk, you go to jail—but doing it through a fume hood is effectively the same environmental outcome.
Over time, I was able to convince many people to do the right thing. Fire marshals supported this approach and began enforcing it. The EPA also recognized the importance of proper solvent handling and adopted similar practices. In fact, one of the first things the EPA did was purchase Eco Funnels for their laboratories.
Within a few years, we knew the company would be profitable.
But being who I am, I’m always thinking about the next innovation. I started exploring antimicrobial technologies—specifically hypochlorous acid and chloramine-based compounds for infection control. That led me to start building another company, NovaBay Pharmaceuticals.
Initially, I incubated NovaBay within CP Lab Safety for several months—close to a year—before formally launching it. Around the year 2000, I transitioned fully to NovaBay. My wife took over CP Lab Safety and successfully grew the company, while I focused entirely on NovaBay.
The initial funding for NovaBay actually came from CP Lab Safety.
At NovaBay, we developed treatments targeting infections such as diabetic ulcers, venous ulcers, and pressure ulcers. Ultimately, one of our key products reached the market—Avenova, also known as NeutroPhase—a leading treatment for blepharitis, an infection of the eyelid.
During that time, I built numerous strategic partnerships with companies such as Alcon, Novartis, Galderma, Virbac China, Pioneer Pharma, and Pung Pharmaceutical in Korea. I was on the plane with my business development guy all the time.
David Brühlmann [00:15:57]:
I imagine that must have been quite a stressful period—quite exciting at the same time.
Ron Najafi [00:16:04]:
Exactly. Attending lots of BIO conferences, attending many BIO-Europe conferences, and also attending Arab Health in Dubai. A lot of partnerships came from those conferences.
We had very extensive partnerships with Alcon, Novartis, and Galderma. When Novartis acquired Alcon, within about a year or so, they decided to cancel the contract.
We had a very extensive contract, and upon its cancellation, I had to let people go. At the time, we had roughly 60 employees at NovaBay. I had to let about a dozen people go, which was a very painful thing to do.
David Brühlmann [00:16:47]:
Oh, that’s a difficult thing to do.
Ron Najafi [00:16:50]:
But on the spot, I made a decision. I said, we have a lot of equipment—we have extensive analytical capabilities. We had NMR—nuclear magnetic resonance spectroscopy—we had mass spectrometry, and we also had strong microbiology capabilities.
I said to the people I was planning to lay off, “Would you like to stay on? I will build a CRO around you.” At the time, we were in Emeryville, and I said, “We can call it Emery Pharma or Emeryville Pharmaceutical Services.”
Out of the dozen people, some accepted the severance package and left, but several said, “No, we want to stay.” They chose to remain and be involved with both NovaBay and the new CRO.
So essentially, Emery Pharma was born in 2011.
David Brühlmann [00:17:39]:
That’s an exciting story. I mean, what a fascinating journey you’ve been on.
Ron Najafi [00:17:44]:
It was really a case of turning death into life at that moment. Upon receiving that notice, we essentially formed a new company. I remember going to Emeryville City Hall in California, filing for the name, and officially registering the company. That was a meaningful moment. In 2015, we experienced some clinical setbacks at NovaBay, although we also had success with Avenova. In fact, we were generating millions of dollars in revenue.
However, the composition of my board had changed. Some of my strongest supporters had retired, and new board members had joined. There were disagreements at the board level. One of the board members, who is an accountant, I won't mention his name. Since this is going to be made public, everybody probably will know who that is. Basically, he spearheaded essentially a change in strategy. He wanted to get rid of all the people with lab coat. He wanted to get rid of Emery Pharma as the subsidiary of Novo Bay. And I was in disagreement. Basically the battle of strategy. I lost in that battle. Part of that loss - I also had to throw in my resignation. And the thinking was, upon my resignation, an announcement of downsizing of the company. We were public, by the way, I took the company public, NovaBay. In 2007, we took the company public. In 2008, I opened the stock market, American Stock Exchange. It's on my personal YouTube channel. The video of opening of the stock market also another big memorable event.
David Brühlmann [00:19:27]:
Wow, that’s amazing. Very fascinating.
Ron Najafi [00:19:31]:
But let me just wrap up. So basically, on the day of the announcement, instead of expecting the stock to go up, it actually fell—because biotech is essentially rooted in hopes and expectations, and that shift was not well received.
So I left. In November 2015, I departed NovaBay and took over Emery Pharma. I then focused on growing Emery Pharma and moved the company to Alameda, California, where we are today—about 20 scientists strong. At Emery Pharma, we do what very few CROs can do. And I can get into that a little bit later if you’d like.
David Brühlmann [00:20:10]:
Absolutely—we will get into that a bit later. I would also like to ask a few follow-up questions about your entrepreneurial journey, because you clearly have a lot to share. But we’ll return to that later in the interview.
For now, I’d like to dive deeper into the science. You mentioned that CMC has three components: Chemistry, Manufacturing, and Controls. So let’s focus on the “Controls” aspect.
Impurity testing has been a major part of your career for many years. Before we get into the story that made you—shall I say—well known, tell us first: what are the main impurities scientists need to watch for in bioprocessing?
Ron Najafi [00:20:56]:
Excellent question. This is an area that is very near and dear to my heart. For example, in DNA synthesis—during my time at Applied Biosystems—we were synthesizing DNA primers. Any bifunctional impurities that enter the reaction can participate in chain extension and effectively propagate through the synthesis. These impurities amplify their impact, so they must be eliminated. Even levels below 0.1% may not be acceptable.
So for DNA synthesis—or any polymerization process—you have to be extremely careful about impurities, especially bifunctional ones that can actively participate in the reaction.
More recently, my work with nitrosamines became a major, newsworthy event—one that ultimately led to my appearance on national television on January 9, 2020, on CBS News, alongside the head of the FDA.
That situation began when we were contacted by a pharmacy in Connecticut called Valisure. They were testing Zantac, which contains ranitidine as the active ingredient.
They were using gas chromatography, where the sample is heated significantly to volatilize compounds for analysis. During testing, they observed extremely high levels of nitrosamines—specifically N-nitrosodimethylamine (NDMA)—in the range of millions of nanograms, which is completely unacceptable.
For context, according to FDA guidelines, the acceptable daily intake limit for NDMA is 96 nanograms per day, assuming lifetime exposure over decades with minimal cancer risk.
So finding millions of nanograms in a single dose was astonishing.
Valisure became very concerned and issued a press release announcing their findings. As a result, many manufacturers voluntarily pulled their ranitidine (Zantac) products from the market.
We chose not to be part of that announcement. In fact, Valisure asked us to join the press release—but we declined. And because we said we needed to do more investigation, we weren’t fully confident in the initial results. We believed the findings were influenced by excessive heating of the ranitidine during analysis.
So we initiated our own internal investigation to understand what was really happening.
Our investigation effectively unraveled the mechanism behind ranitidine degradation. Ranitidine was breaking down, and one of its degradation products was NDMA.
On December 10, the FDA issued a press release stating that if NDMA impurity levels were below 96 nanograms per day, the product could remain on the market. This guidance was directed at manufacturers at the time.
However, we determined that this interpretation was incorrect. We pointed out to the FDA that NDMA in this case was not simply an impurity—it was being formed as a degradation product from ranitidine itself.
This was, of course, a significant and difficult finding for manufacturers of ranitidine.
Eventually, I was invited to appear on national television, where the head of the FDA was also present. During that discussion, the FDA indicated that further investigation was needed and that they were not yet certain about Emery Pharma’s findings.
They proceeded with their own investigation, and approximately three months later, they confirmed that our conclusions were correct. In fact, they sent us a formal letter acknowledging and validating our findings.
As a result of this work, we became deeply involved not only in root cause analysis of nitrosamines in ranitidine but also in risk and root cause analysis for other drugs, such as valsartan, a blood pressure medication.
Through this work, I developed deep expertise in the synthetic pathways and mechanisms that can lead to nitrosamine formation in pharmaceuticals.
Today, we are considered among the leading experts in nitrosamine analysis and mitigation. We’ve been invited to present at major organizations and companies, including Genentech, Gilead, Exelixis, and others. We have built significant expertise in this area.
In terms of impurities, this goes beyond typical concerns like DNA-related issues in synthesis. Here, we are dealing with genotoxic impurities—compounds that can damage genetic material and potentially cause cancer.
NDMA is a well-known genotoxic compound. It has been shown to cause cancer in every animal model in which it has been tested. So it is absolutely critical to control and eliminate it from pharmaceutical products. Strong analytical controls and risk assessments are essential. We now advise many companies—currently working with over a dozen organizations that are developing drugs for market—on nitrosamine risk assessment and mitigation strategies.
And I don’t want to alarm your audience, but if you’re developing a drug and haven’t yet conducted a nitrosamine risk assessment—this is something you need to start thinking about now.
David Brühlmann [00:26:29]:
I have a question about that, Ron, because I’m sure some of the listeners are wondering: where do nitrosamines actually come from? If I’m developing a novel process, what do I need to watch out for? Are these coming from raw materials, reagents, or somewhere else?
Ron Najafi [00:26:47]:
That’s a very valid question. If your process involves secondary, tertiary, or even quaternary amines, and you also have oxidative conditions—particularly involving chloramine species or similar oxidants—you have the potential to form nitrosamines.
One key risk factor is the presence of nitrite sources—especially sodium nitrite, which is a major contributor. Sodium nitrite can be present at low levels even in common excipients, such as microcrystalline cellulose, which is widely used in tablet formulations. The reaction essentially involves the formation of a nitrosonium ion (NO⁺), which reacts with secondary or tertiary amines to form nitrosamines.
For those interested in learning more, I recommend visiting our website—we’ve published extensive material on this topic. I’ve also recorded a detailed YouTube presentation focused specifically on nitrosamine formation and control. And of course, we’re always open to engaging with others in the industry to help address these challenges.
David Brühlmann [00:27:52]:
So this suggests that nitrosamine risk is greater in traditional small-molecule pharmaceutical processes and less of a concern in biologics—is that correct?
Ron Najafi [00:28:03]:
It’s less of a risk in biologics. But if you have a small molecule with secondary, tertiary, or quaternary amines in your process, you absolutely need to be vigilant. FDA reviewers have seen it all—they are very sensitive to this issue.
As of August 2025, every manufacturer with a product on the market—or in development—must submit a very thorough nitrosamine risk assessment. This includes evaluating incoming raw materials, the chemistry, and the manufacturing process to ensure that no nitrosamines are formed or introduced.
We had a very instructive case with one of our clients. They performed only a superficial risk assessment. We advised against that approach and recommended conducting proper analytical testing to confirm the absence of nitrosamines.
Instead, they proceeded with manufacturing—spending approximately $6 million to produce three batches. At the final stage, the FDA required them to perform testing. When they did, they found NDMA at 11,000 nanograms in a single pill that was supposed to be 40 mg.
That’s why it’s far better to conduct a thorough risk assessment early.
At Emery Pharma, we often perform an initial, high-level risk assessment at no charge. If clients share their process under an NDA, we evaluate it and help them understand the level of risk associated with moving forward based on a superficial versus a comprehensive analysis.
Now, in biologics, nitrosation is much less of a concern. For a nitroso compound derived from a biologic to become genotoxic, it would need to be metabolically activated—typically by cytochrome P450 (CYP) enzymes. However, these enzymes generally cannot accommodate large biologic molecules. So overall, small molecules are significantly more prone to nitrosamine-related risks than biologics.
David Brühlmann [00:30:07]:
And I would add to that, Ron, it’s good practice in general to perform impurity risk assessments. This is what health authorities expect—not just for nitrosamines, but for all types of impurities. For example, leachables and extractables from single-use systems are also important considerations.
Ron Najafi [00:30:28]:
Absolutely. Those compounds can leach into the product and become part of the final formulation. Many single-use plastics contain plasticizers and stabilizers, which are not ideal for patient exposure. So it’s critical to have proper controls in place.
David Brühlmann [00:30:46]:
Ron Najafi’s journey from bench chemist to serial founder is a compelling reminder of what’s possible when scientific depth meets entrepreneurial drive. In Part Two, we’ll go deeper into the practical side—exploring CRO partnerships, the future of pharmaceutical analytics, and the lessons learned from more than three decades of building companies.
If this episode brought you value, please leave a review on Apple Podcasts or your preferred platform. Thank you for tuning in today, and I’ll see you next time.
All right, smart scientists—that’s all for today on the Smart Biotech Scientist Podcast. Thank you for joining us on your journey to bioprocess mastery. If you enjoyed this episode, please leave a review on Apple Podcasts or your favorite podcast platform. By doing so, we can empower more scientists like you. For additional bioprocessing tips, visit smartbiotechscientist.com. Stay tuned for more inspiring biotech insights in our next episode. Until then, let’s continue to smarten up biotech.
Disclaimer: This transcript was generated with the assistance of artificial intelligence. While efforts have been made to ensure accuracy, it may contain errors, omissions, or misinterpretations. The text has been lightly edited and optimized for readability and flow. Please do not rely on it as a verbatim record.
Book a free consultation to help you get started on any questions you may have about bioprocess development: https://bruehlmann-consulting.com/call
About Ron Najafi
Dr. Ramin (Ron) Najafi is a scientist and entrepreneur with over 30 years of experience in the pharmaceutical and biotechnology industries. He is the Founder of CP Lab Safety, a laboratory safety–focused company dedicated to improving environmental health and safe lab practices. He is also the Founder, President, and CEO of Emery Pharma, where he leads a team deeply committed to advancing science, safety, and quality in drug development.
Under his leadership, Emery Pharma provides expert support in CMC and bioanalytical testing, including PK, PD, and TK studies, helping clients meet rigorous regulatory and scientific standards.
Connect with Ron Najafi on LinkedIn.
If you’re interested in this topic, check out these episodes on building a robust scale-up strategy. To get it right, you need to view the process from multiple angles—regulatory, digital, and operational.
Episodes 23 - 24: Strategies for Success: Master CMC Development with Gene Lee
Episodes 57 - 58: Crafting a Solid CMC Strategy: Key Factors and Common Pitfalls with Matthias Müllner
Episodes 139 - 140: Regulatory Secrets Revealed: Why Your CMC Strategy Could Make or Break Your Biotech Startup with Rivka Zaibel
Episodes 189 - 190: Why Smart Biotech Founders Plan CMC First (While Competitors Burn Cash Later)
Episodes 199 - 200: Mastering Quality by Design: From Product Failures to Commercial Success in Biologics CMC Development
Episodes 203 - 204: Mastering CRO Selection: Essential Questions for CMC Analytical Development with Daniel Galbraith
Episodes 231 - 232: From IND to BLA: The Biologics CMC Decisions That Determine Regulatory Success with Henri Kornmann
Below, you’ll find a curated collection of resources, technical guides, and regulatory links shared by our guest.
David Brühlmann is a strategic advisor who helps C-level biotech leaders reduce development and manufacturing costs to make life-saving therapies accessible to more patients worldwide.
He is also a biotech technology innovation coach, technology transfer leader, and host of the Smart Biotech Scientist podcast—the go-to podcast for biotech scientists who want to master biopharma CMC development and biomanufacturing.
Hear It From The Horse’s Mouth
Want to listen to the full interview? Go to Smart Biotech Scientist Podcast.
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What’s the real difference between a shake flask, a microtiter plate, and a full-scale bioreactor—and why do so many experiments go sideways, even when the SOP looks perfect?
If you’ve ever scratched your head about irreproducible results or the so-called “black box” of pre-culture history, you’re not alone. In this episode, host David Brühlmann sits down with Tibor Anderlei, a pioneer in orbital shaking technology, whose career spans from startup founder to long-haul leader at Kühner. Tibor isn’t just the guy who helped design the tools; he’s spent decades troubleshooting with everyone from viral vector scientists to cultivated meat innovators.
All the new modalities you mentioned have one thing in common: they are more shear-sensitive than, for example, bacteria or CHO cells. Orbital shaken bioreactors are very suitable for shear-sensitive cells or systems, and the main reason is that they are surface-aerated, meaning we have nearly no bubbles. And bubbles rise, they burst, and they create very high local power input when they burst, which can damage the cells.
David Brühlmann [00:00:36]:
Welcome back. In Part one, Tibor Anderlei walked us through the hidden physics of shake flasks and microtiter plates, and why reproducibility challenges are so often rooted in fundamentals that get overlooked, such as the shaking diameter. Now in Part two, we continue our conversation and go deeper—exploring next-generation modalities, cultivated meat, and the surprising range of fields where shaking technology is making an impact beyond bioprocessing, plus leadership lessons from three decades in the industry. Let's continue.
I would like to dive a bit deeper into aeration, since you mentioned that this is one of the pitfalls where people work under oxygen-limited conditions. One way to measure aeration is by dissolved oxygen, like in bioreactors, for instance. Can you tell us what the best way is? Is DO sufficient, or should you do more sophisticated measurements? What is your recommendation there?
Tibor Anderlei [00:02:55]:
It's a little bit questioned: what is the difference between DO, for example, or another parameter? In my opinion, the more relevant parameters are the oxygen transfer rate (OTR) and the carbon dioxide transfer rate (CTR). I often hear people say, “I have DO—why should I also consider OTR and CTR?” I usually compare it with a bathtub: the water level corresponds to the concentration, and DO is the concentration, while the change in water level over time is a rate—that is the oxygen transfer rate.
With a rate, you can tell whether the water level is increasing, decreasing, or staying stable—you gain insight into the future. You can ask yourself: what would you like to know when leaving the house for five minutes while filling a bathtub? In my opinion, the rate is much more informative than the water level (DO).
And furthermore, the advantage of measuring respiration activity, such as oxygen transfer rate (OTR) and carbon dioxide transfer rate (CTR), is that you can measure them outside the sterile boundary of your bioreactor, so you do not have any contamination risk compared to sensors measuring inside the bioreactor itself. And last but not least, the respiration quotient between CTR and OTR—so carbon dioxide transfer rate divided by oxygen transfer rate—also provides information about which carbon source is being consumed. For example, an RQ around 1 indicates glucose, while an RQ around 0.6 indicates, for example, ethanol. With this, you can start to balance a bioprocess, which is very interesting for metabolic flux analysis, for example.
And last but not least, if you want to compare different bioreactor systems, such as a shake flask versus a wave system, you cannot do that with a DO value—you cannot compare them directly. But you can compare bioreactors by using the oxygen transfer rate. So I think OTR and CTR are much more valuable parameters than, for example, DO.
David Brühlmann [00:05:17]:
And what is the minimal scale required to measure oxygen transfer rate or carbon dioxide transfer rate?
Tibor Anderlei [00:05:25]:
Nowadays, we are capable of measuring OTR even in microtiter plates. We have a system called MicroTOM, where we measure the OTR in each well of a 96-well deep-well plate. So that represents the minimum scale already. The maximum scale is large—bioreactors, which in the microbial world have been standard for decades, where OTR and CTR are routinely measured and used for control. In the cell culture world, however, this is not yet as standard as in microbial systems.
David Brühlmann [00:06:03]:
I agree—I haven’t seen this as much when I was working with microtiter plate or spin tube experiments. It’s more common in bioreactors, especially in the cell culture field. But it’s good to know that it is possible to measure these parameters at much smaller scales. I’d like to touch on PAT as well, because many people are using microtiter plates to measure different parameters—hopefully even in real time or at least semi–real time. What is the situation there? What kind of PAT are you developing or seeing companies use at that very small scale?
Tibor Anderlei [00:06:47]:
Maybe in microtiter plates I would also include shake flasks in that context. In my opinion, it is very relevant to have PAT already at small scale, because online monitoring of precultures for larger bioreactors is still not carried out very often. During my time at AC Biotec, for example, we carried out many Pichia pastoris cultivations in stirred bioreactors. We were often confronted with poor reproducibility in these runs. Initially, we focused on optimizing the main culture in the stirred bioreactor, but we later learned that the variability originated from the preculture. We also realized that transferring based on OD measurements was not reliable. With Pichia, high OD values are reached, making OD determination less robust. Instead, we shifted to transferring cultures based on OTR—for example, at an OTR of 0.03 mol·L⁻¹·h⁻¹—which led to the desired reproducibility.
In my opinion, the history and condition of the preculture are extremely important. Even today, despite advances in modeling and digital twins, I still feel that preculture conditions are not given enough attention.
David Brühlmann [00:08:28]:
Yes, I fully agree, the preculture is extremely important. I would like to talk about other modalities, because these systems have traditionally been used in the microbial space and in, I’d say, CHO or mammalian cell culture. Now we are seeing viral vectors, CAR-T, mRNA. We also see cultivated meat. How is the landscape changing or the technology evolving? What are you seeing among your different customers?
Tibor Anderlei [00:08:59]:
For me it’s a little bit easier, I would say, because at the shake flask level I do not see so many differences. All the new modalities you mentioned have one thing in common: they are more shear-sensitive than, for example, bacteria or CHO cells. Orbital shaken bioreactors are very suitable for shear-sensitive cells or systems. The main reason is that they are surface-aerated, meaning we have nearly no bubbles. Bubbles rise, burst, and create very high local power input when they burst, which can damage the cells. So I do not see major differences at the shake flask scale. Furthermore, real-time monitoring is always beneficial. When establishing a new biological system in the lab, you can analyze and optimize screening or cultivation conditions much faster. Online data also helps reduce the number of offline samples. You take samples at points of interest—for example, when an online signal like OTR shows a dip—so fewer samples mean less analysis time and lower costs.
You also mentioned the cultivated meat field. Here too, I do not see major differences at small scale. However, the food industry is very price-sensitive, especially regarding media and production equipment. Therefore, significant effort is focused on developing cost-effective media. Due to time pressure, media testing should be parallelized, and in my opinion, shifted to microtiter plate scale very early. Investing in online technology at this stage can significantly accelerate development.
Because of cost sensitivity, expensive consumables such as specialized flasks or plates are not practical. That is why, when we developed systems like the CunaTOM or MicroTOM, we consistently use standard plates and standard shake flasks to keep operating costs low for the customer. I believe that is key in this field also.
David Brühlmann [00:11:45]:
Besides cultivation for cell culture processes, do you also see people using your systems for other applications we have not touched upon yet? Can they be used in different areas?
Tibor Anderlei [00:12:01]:
Oh yeah, we have a lot of different customers in that field. One area is mixing. When you use orbital shakers for mixing, you always work with a closed system. For example, a bag can remain closed, whereas if you use a stirrer, you need to open the system and insert it. So with a shaker, you can mix in a closed system, which is a major advantage. For instance, we have a customer—a large company in the Asian region—using our system for liquid crystal mixing, used in mobile phones, TVs, and similar applications. That is a completely different market.
We also increasingly see customers using our systems for storage. For example, fermentation broths containing cells often need to be stored while still being gently mixed. In some cases, this is done manually in cold rooms by shaking bags, but that is not a controlled or defined process. Here, our systems provide a defined and reproducible way to handle such applications. This also applies to thawing processes—for example, thawing fermentation broths—which must be done in a controlled manner. Our systems are also widely used in these contexts.
David Brühlmann [00:13:28]:
That’s exciting, because it’s not what people initially think of when they hear about shaken bioreactors and microtiter plates. It shows how broad the applications really are.
Tibor Anderlei [00:13:40]:
Yes, definitely.
David Brühlmann [00:13:42]:
I would like to circle back to your entrepreneurial experience. We discussed this at the beginning of our conversation—you founded AC Biotec and have now been with Kühner for two decades. I’d be interested in your perspective. At Kühner, you are competing with larger players in the field, such as Sartorius, Cytiva, and Thermo Fisher. What have you learned as an entrepreneur and leader to not only survive but thrive in such a dynamic market?
Tibor Anderlei [00:14:20]:
That is a combination of questions. First of all, yes, we are competing with companies like Sartorius, Cytiva, and Thermo Fisher. As Kühner, we must be innovative and agile, and we must stay very close to our customers. I think that is something we do quite well. On the one hand, these are competitors, but on the other hand, they are also customers, as they have acquired companies that were already working with us. So there is always a dual relationship.
I also believe that pharmaceutical and biotech companies benefit from maintaining flexibility and independence in their supplier landscape. This creates opportunities for smaller and mid-sized companies like ours to compete with global players. In that sense, recent events such as the COVID-19 pandemic have reinforced the importance of supply chain diversity and resilience.
David Brühlmann [00:15:35]:
At least dual sourcing is a pretty good idea. This leads me to the next question, because I would love to hear about your leadership experience and understand what your most important leadership lesson is that you have learned about building successful technical organizations in biotech.
Tibor Anderlei [00:15:57]:
Okay. Of course, I had experience with a startup, and then maybe I’m boring because I went to another company, Kühner Shaker, and I have been there for 20 years. From my experience, when you launch a company, you should always have a product idea in mind. Being only a service provider in the beginning is good to generate faster cash flow, which is needed, but you should also use that time to develop a product.
A second thing I would say is that you should learn to trust your gut feeling. Of course, you have to analyze as much as possible before making a decision, but you cannot analyze everything—that’s not possible. And in many cases, a complete analysis takes a long time and does not significantly change the final decision.
Third, I would say that I initially underestimated the importance of personal chemistry between business partners. A good relationship between partners is a very important factor for successful collaboration and trust, which is also very important to me. In general, I’m very glad to be working in the field of biotechnology, because you nearly always work with very nice people.
David Brühlmann [00:17:38]:
Yes, I agree—biotech is a great place to work. I’ve met many great people throughout my career.
Tibor Anderlei [00:17:46]:
Definitely.
David Brühlmann [00:17:47]:
As we are wrapping up, Tibor, I’d like to make this actionable for the Smart Biotech Scientist listeners. What is one piece of advice you would give them if they are starting out using microtiter plates or shake flasks, or trying to make these systems work well?
Tibor Anderlei [00:18:09]:
You know I like shaking diameter—that is one important aspect. But more generally, I would say: recognize the importance of shaken bioreactors and define your screening conditions very carefully. I would also strongly recommend using online measurement tools even at small scale. At larger scales, online monitoring is common, but at small scale it is still underutilized.
David Brühlmann [00:18:39]:
Fantastic. Before we wrap up, Tibor—what is one question I haven’t asked that you would like to share with the biotech community?
Tibor Anderlei [00:18:48]:
I think you already covered many important topics. Maybe I can leave one key takeaway: when shaken bioreactors such as shake flasks, tubes, or microtiter plates are applied correctly, they provide an easy-to-handle, inexpensive, automatable tool with low running costs and scalable results.
I believe knowledge at small scale is critical, and this topic should also be taught more at universities. We also offer a webinar series on this topic, where my colleague David Flitsch explains over several sessions how to properly handle microtiter plates, tubes, and shake flasks.
David Brühlmann [00:19:57]:
There you have it—Smart Biotech Scientist, a great takeaway. Thank you, Tibor, for highlighting how shaken bioreactor systems can be such a powerful tool. Where can people connect with you and access your resources?
Tibor Anderlei [00:20:16]:
You can reach me via LinkedIn, and you can also meet me and my team at conferences and trade fairs. Our booth features rings in the logo, representing orbital motion—since we focus on orbital shaking. LinkedIn is probably the easiest way to connect.
David Brühlmann [00:20:44]:
Fantastic. I’ll include the links in the show notes, so please take the opportunity to reach out to Tibor and his team. Tibor, thank you again for sharing your expertise, passion, and practical insights.
Tibor Anderlei [00:21:04]:
Thank you very much, David. I’m looking forward to the next podcast.
David Brühlmann [00:21:14]:
Tibor Anderlei’s combination of scientific rigor, entrepreneurial experience, and customer-facing work makes him a rare voice in this space. Whether you’re troubleshooting scale-up or preparing a CDMO transfer, today’s conversation provides a valuable framework.
Thanks for listening to the Smart Biotech Scientist Podcast. If this episode was useful, please leave a review on Apple Podcasts or your favorite platform and share it with a colleague. Stay tuned for more biotech insights in our next episode. Until then, let’s continue to smarten up biotech.
Disclaimer: This transcript was generated with the assistance of artificial intelligence. While efforts have been made to ensure accuracy, it may contain errors, omissions, or misinterpretations. The text has been lightly edited and optimized for readability and flow. Please do not rely on it as a verbatim record.
Book a free consultation to help you get started on any questions you may have about bioprocess development: https://bruehlmann-consulting.com/call
About Tibor Anderlei
Tibor Anderlei is a passionate advocate for improving how bioprocess development begins—at the small scale. With a career spanning academic research, startup innovation, and industry leadership, he focuses on the often-overlooked role of shake flasks and orbital shaken bioreactors in critical early decisions.
He works to raise awareness of their importance in education and industry, helping teams build more reliable and scalable bioprocesses from the start.
Connect with Tibor Anderlei on LinkedIn.
If you’re interested in this topic, check out these episodes on building a robust scale-up strategy. To get it right, you need to view the process from multiple angles—regulatory, digital, and operational.
Episode 03 - 04: How to Master Biotech Scale-up Without Guesswork with Leonardo Sibilio
Episode 25 - 26: 9 Critical Steps for a Seamless Transition to Large-Scale Production
Episode 231-232: From IND to BLA: The Biologics CMC Decisions That Determine Regulatory Success with Henri Kornmann
Episode 233-234: Why Most Bioprocess Automation Projects Fail with Anthony Catacchio
Episode 237-238: High-Throughput Microbial Screening with Sebastian Blum
Below, you’ll find a curated collection of resources shared by our guest.
David Brühlmann is a strategic advisor who helps C-level biotech leaders reduce development and manufacturing costs to make life-saving therapies accessible to more patients worldwide.
He is also a biotech technology innovation coach, technology transfer leader, and host of the Smart Biotech Scientist podcast—the go-to podcast for biotech scientists who want to master biopharma CMC development and biomanufacturing.
Hear It From The Horse’s Mouth
Want to listen to the full interview? Go to Smart Biotech Scientist Podcast.
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In bioprocess development, orbital-shaken bioreactors—shake flasks, spin tubes, and microtiter plates—are the unsung backbone powering industry decisions about production strains and media. Yet, when scientists attempt to scale up their textbook-perfect experiments, the results often unravel, leaving teams scrambling for answers.
This episode features Tibor Anderlei, a pioneer who transformed shake flask monitoring from a PhD curiosity into an essential industry tool. After co-founding AC Biotech and leading work at Kühner Shaker, Tibor now steers customer success, translating three decades of hands-on expertise into practical solutions for scientists battling the reproducibility and scale-up puzzle.
Automation is a trend in the field of bioprocessing or screening. The advantage, I would say, for microtiter plates is that they follow more or less already a standardized format like the ANSI or SBS format. And a standardized format is very important for us as a supplier for automation equipment like our BELUGA machine or MPS-Z. Automated standardization is key.
David Brühlmann [00:00:30]:
Imagine building the perfect cell culture experiment. Clean data, reproducible results, textbook performance. Only to watch it completely fall apart the moment you scale up. If that scenario sounds familiar, you're not alone.
Today's guest has spent over three decades solving exactly that problem, from microtiter plates and spin tubes to shake flasks and beyond. Tibor Anderlei pioneered online monitoring in shake flasks during his PhD, co-founded AC Biotec, and now leads customer success at Kühner Shaker, offering specialized support in shaking cultivation technology. Welcome to Part one. Welcome, Tibor. It's great to have you on today.
Tibor Anderlei [00:02:31]:
Yeah, thank you. And Grüezi, David—Hello, David—and thank you very much for inviting me. I'm very pleased and excited to be here on your podcast.
David Brühlmann [00:02:42]:
It's a pleasure to have you on, Tibor. It's been a while—we've been talking about it and now we finally made it happen. So I'm really excited. It's like a good old Bordeaux wine—it takes some time to reach maturation, and then when you drink it, it's a good wine. That's the same with having a podcast interview. Tibor, share something that you believe about bioprocess development that most people disagree with.
Tibor Anderlei [00:03:11]:
I like this question, and I would say orbital shaken bioreactors like shake flasks, tubes, and microtiter plates are the most important bioreactors—maybe besides stirred bioreactors, as you know. They are very important because very fundamental decisions regarding production strains and media composition are made in these bioreactors during the screening phase. And in my opinion, also the information the user gets by using these orbital shaken bioreactors is so essential. However, these bioreactors are not treated like that. For example, the topic of cultivation conditions in orbital shaken bioreactors is not always part of education at universities and schools.
David Brühlmann [00:04:00]:
You are making an excellent point. I think I have not heard about these bioreactors during my studies—very spot on. Before we dive further into the technology, I'd like to talk about yourself first. Take us back to your PhD days and tell us what sparked your interest in bioprocessing, and what were some pivotal moments along your long career that led you to your current role at Kühner?
Tibor Anderlei [00:04:27]:
My career started at the Technical University of Aachen in Germany (RWTH Aachen University), where I studied biochemical engineering. Just after I finished my final exam, a new professor started there—his name was Jochen Büchs—and he set up a brand-new lab. This opportunity was very interesting: building up a lab together with a team, and of course working on his new research topic, which was small-scale cultivation.
Professor Büchs came from BASF SE to the university, and he also brought some older equipment from the company, as they had renewed their labs. One system was a prototype of an online measuring device for oxygen transfer rate in shake flasks. He had developed this system during his time in industry.
I can tell you—it was a prototype. It still used very expensive Ingold probes for oxygen sensors, originally designed for stainless steel bioreactors, and even an Atari computer for data acquisition. But for me, the opportunity to start my research with online monitoring equipment was very clear, so I took it.
I further developed the system—expanding the prototype by adding carbon dioxide transfer rate measurements, and of course implementing robust software together with an external company. Looking back, was it a revolutionary technology? At that time, there was essentially no online measuring tool available for shake flasks. So having an online signal already at this scale was very important—and in my opinion, a kind of revolution.
David Brühlmann [00:06:24]:
What made you realize that this technology you were working on could potentially revolutionize small-scale bioprocessing?
Tibor Anderlei [00:06:33]:
Was it a revolution? That is a real question. At that time, there was simply no online measuring tool on the market for shake flasks. So having an online signal already at that scale was very important—and I would say a kind of revolution.
During my PhD, while setting up the lab and working with a company on developing a commercial product, I always had the idea in mind to start a company myself.
At the Biotechnology Conference 2000 in Berlin, I met Simon Curvers. He was a PhD student from the Research Center Jülich, near Aachen, and he had the same idea. Over about a year, we had several meetings and discussions, and eventually founded AC Biotec.
We focused on contract research and contract manufacturing, with bioreactors up to 300 liters. We mainly worked with yeast cultivation, especially Pichia pastoris.
After about five years, I left the company because I realized we were too small for this kind of business, and we did not have our own product idea to attract investors. However, I remained connected to AC Biotec.
After that, I moved to Kühner Shaker. Since the AC Biotec team already had strong expertise in shaken cultures, we had organized shaking seminars together with Markus Kühner, the CEO of Kühner Shaker. I also knew him from earlier collaborations with Professor Büchs.
As early as 1999 in Basel and around 2000–2001 in New York, Kühner and Professor Büchs organized conferences on shake flask and microtiter plate applications. Markus Kühner had a clear vision: to support science not only by building reliable equipment, but also by providing strong scientific support to customers.
I joined Kühner Shaker in 2006, and I’ve now been with the company for about 20 years. I am the CSO, responsible for the customer interface—which includes sales, service, and support. Support in our case includes GMP topics, troubleshooting, marketing, and applied technology. And I think we will talk more about these 30 years of experience in small-scale cultivation.
David Brühlmann [00:09:29]:
Yeah, absolutely. Let's unpack the onion, because there is so much to talk about with this technology, and a lot of people are using shaking cultures in one way or another. So let's tackle the elephant in the room that frustrates many scientists: why do shake flask and microtiter plate experiments that work well in publications often fail when someone tries to reproduce them in their own lab?
Tibor Anderlei [00:09:59]:
I think that's really a nice and important question. And I would say that a lot can be explained by the lack of knowledge about these bioreactors. The reason for this is that cultivation conditions in orbital shaken bioreactors are not a major topic during the education phase, as I said before. This has luckily changed a little bit over the last years, but it's still far from optimal.
I can give you one example. There is a very nice publication from Gesa Brauneck. She is from the Technical University of Aachen, from the lab of Professor Magnus, who is the successor of Professor Büchs. She analyzed publications dealing with aerobic cultivations of E. coli for optimal production strains. She looked at the 15 most recent articles and gathered information regarding their cultivation conditions in shake flasks. And now David, I can ask you some questions—are you prepared for that?
David Brühlmann [00:11:11]:
Yes, you're putting me on the spot now. Let's do it.
Tibor Anderlei [00:11:14]:
Okay. So how many of the 15 most recent publications mentioned the media composition? You can give a number between 0 and 100%.
David Brühlmann [00:11:27]:
I would say media is important—I’d say at least 60% cited media composition.
Tibor Anderlei [00:11:35]:
It's even more—they are really good. It was 100%.
David Brühlmann [00:11:40]:
Oh, excellent.
Tibor Anderlei [00:11:41]:
And how many mentioned the cultivation temperature?
David Brühlmann [00:11:45]:
Well, if media is 100%, I would say it's close to 100%.
Tibor Anderlei [00:11:51]:
You are perfectly right. So now we come to more specific parameters regarding shake flasks. How many mentioned shaking speed?
David Brühlmann [00:12:02]:
I would say it's less than 50%.
Tibor Anderlei [00:12:04]:
Actually, it's higher—80%. And what about the filling volume—how much liquid they put into the shake flask?
David Brühlmann [00:12:13]:
Let’s say 70%.
Tibor Anderlei [00:12:14]:
You are close—65%. And the shake flask size—whether they used 125 mL, 250 mL, or 1 L flasks?
David Brühlmann [00:12:24]:
There I would say close to 100%.
Tibor Anderlei [00:12:27]:
No, it's only 55%. And last but not least—how many mentioned the shaking diameter?
David Brühlmann [00:12:35]:
Oh, I think this is a parameter not many people mention. I would say below 50%.
Tibor Anderlei [00:12:41]:
Now you are far above—it is actually 0%. And that is nothing new to me. I always say in seminars that more than 90% of publications do not mention the shaking diameter. This shows me that the shaking diameter seems to be not an important factor for many users. But I can tell you—it is as essential as, for example, the type of stirrer in a stirred bioreactor.
If you use a Rushton turbine or a pitched-blade impeller, everybody will mention that. But shaking diameter—you don’t see it. And one important point here: you can easily achieve 30% to 50% higher oxygen transfer by using a shaking diameter of 50 mm instead of 25 mm at the same shaking speed. So, coming back to your question—if you do not know the shaking diameter, you simply cannot reproduce the experiments from a publication.
David Brühlmann [00:13:42]:
Yes, this is an excellent point. So details matter—there is no doubt about that. Microtiter plates, tubes, and shake flasks—well, shake flasks have been around for a long time, but the others have become increasingly popular for high-throughput screening. But they come with their own set of challenges. So in addition to what you've just mentioned, Tibor, what other challenges do scientists need to watch out for in order to succeed with these experiments?
Tibor Anderlei [00:14:13]:
That question leads to a long answer. I would say of course you mentioned microtiter plates and tubes, so I would say both systems are quite popular in the moment. And why? Because they can be automated. Automation is a trend in the field of bioprocessing or screening. The advantage I would say for microtiter plates is that they follow more or less already a standardized format like the ANSI, SLAS or SBS format. And a standardized format is very important for us as a supplier for automation equipment like our Beluga machine or MPS-Z. Automated standardization is key.
The tubes are also very nice for automation because they can easily be used for cultivation step, for the shaking and cultivating, and for the first downstream process like separation because of their conical bottom shape. Also suppliers of centrifuges are used to this format and have long time experience with it and provide of course a lot of accessories.
The history of the tubes is also interesting because it started at the EPFL in Lausanne where Florian Maria Wurm used the 50 milliliter TPP tube with a membrane filter to cultivate cells and the tube in my opinion is a very good bioreactor for cell cultivation.
The filling volume is about 10–30 mL and the shaking speed depends on the shaking diameter. Again, shaking diameter is between 180 and 300 rpm in order to increase the oxygen transfer. The filling volume is about 10–30 mL and the shaking speed depending on the shaking diameter is about 180 and 300 rpm. In order to increase the oxygen transfer, some users tilt the tubes. But to be honest, I'm not a fan of it. Tilting is more or less like adding a baffle into the tube and that will create higher shear stress on the one hand and foam creation, and especially foam can on the one hand increase the oxygen transfer when you have a fluffy foam, or on the other hand it can decrease the oxygen transfer if you have a very sticky foam. And this leads, in my opinion, to unreproducible results which should be avoided during the screening phase. So I would suggest to shake the tubes always in vertical position.
Also, just a small side note, a few degrees more in tilting or less can have a huge impact on the fluid dynamics. I have read all the publications and posters on cell culture conferences showing very good results using the tube or this bioreactor to simulate even a perfusion process. The publication compared the results with runs in stirred bioreactors and got similar results.
Nowadays the tubes also get competition with for example a 6-well ultra-deep well plate, which also has a filling volume of about 30 milliliter. And now we come to the microtiter plate topic. So in general, microtiter plates have a very huge range, starting from 96-well plates up to 6-well ultra-deep well plates. In my opinion, mostly used are 96 and 24 deep-well plates.
And we can now discuss of course about different influencing factors like the lid, square or round well shape, or which bottom type is better: round, flat, conical. But to be honest, I also want to focus here more on the shaking speed and the shaking diameter. And here I think it is very important. First of all, there is a critical shaking speed you have to overcome to get good mixing in a microtiter plate. This critical shaking speed depends on the filling volume, on the media composition and on the shaking diameter.
The nice thing is that you can calculate this critical shaking speed which is presented by a friend of mine, Wouter A. Duetz, and you can also find the step-by-step calculation in our science room on our website. I think you will also have that in your show notes. The reason for this critical shaking speed is mainly that you need certain centrifugal force to break the surface tension of the liquid.
For example, shaking a microtiter plate with 300 rpm and a relatively small shaking diameter of 12.5 millimeter. So the reason for the critical shaking speed is mainly that you need a certain centrifugal force to break the surface tension of your liquid. And for example, if you have a microtiter plate, a 96-well plate, and you shake it with 300 rpm and 12.5 millimeter shaking diameter, or you let it sit on the clean bench without shaking, the effect will be the same. The effect will be that you have no mixing at all. So at least here you have to shake, for example, 450 rpm to get a mixing effect in the 96-well plate.
So I think this is very important to know that there is a critical shaking speed. And very often I hear the statement small vessels need small shaking diameter. This is, in my opinion, not correct. In the microbial world where high oxygen transfer rates are essential, we suggest to have filling volume lower than 30% of the nominal well volume of a microtiter plate and you shake it with 25 or 50 millimeter, 300 to 400 rpm, more or less standard.
I would say in the world of cell culture this is different. Here the respiration activity of the cells is much lower, I would say 50 to 60 times lower than a yeast cell. And you can fill up the well of a 96 deep-well plate up to 800 microliter or even 1 milliliter. And in this case, and only in my opinion, in this case, you need a shaking diameter of 3 millimeter and a shaking speed of 1000 rpm to get good mixing. And when you reduce the liquid volume again below 800 microliter, then 25 millimeter and 400 rpm is already sufficient, I think.
Now I give you a lot of numbers, I know, but I hope these examples could show you how important the knowledge on the level of small scale system is.
David Brühlmann [00:21:20]:
Let me pause here for a moment because you’ve delivered a ton of valuable information. Just to get our heads around that—because it’s very important to get this right. I’ve done a lot of experiments using this technology, and what you’ve just said, Tibor, is absolutely essential.
Small-scale shaken systems are great. And if you do them well—if you get all these detailed parameters right—they can be a very powerful system because you can test many different conditions in a very short time.
Now this leads me to the next question. If you do this homework and look at all these parameters in such a detailed way, in most cases you can use the data you’re generating and hopefully even predict behavior at larger scale. But I’d be curious—because you speak to a lot of companies and have seen a lot in the industry—what were some of the most spectacular scale-up failures, and why did they fail?
Tibor Anderlei [00:22:22]:
I would say the most common scale-up issue is that users perform their shake flask screening under oxygen-limited conditions. This is typically due to using too high filling volumes and too low shaking speeds.
Screening under these conditions will lead to issues during scale-up. When the system is transferred into a lab-scale stirred bioreactor, oxygen limitation is often no longer present. As a result, the strain behaves differently—ranging from producing no product to producing more product.
Let me give you another example. I had a client developing a bioprocess in shake flasks. Let’s say he observed 100% of his product yield at shake flask scale. However, when scaling up to a stirred bioreactor, he observed only about 70% of the product yield, which was of course disappointing. He contacted me because he knew I could calculate the aeration rate in shake flasks—that is, how much air is actually transferred through the system. I calculated the aeration rate for his setup, and it was approximately 0.5 vvm (volumes of gas per volume of liquid per minute). Typically, users do not know the aeration rate in shake flasks. In microbial processes, they often set bioreactors to 1 vvm as a standard. That is exactly what he had done as well.
My suggestion was to reduce the aeration rate in the stirred bioreactor to 0.5 vvm to match the shake flask conditions. As a result, he recovered more than 90% of his product in the stirred bioreactor. What I want to emphasize is that, in addition to oxygen transfer rate (OTR), mixing time, and power input, ventilation is also a critical scale-up factor. Ventilation relates to the removal of volatile compounds such as CO₂ or ethanol from the system.
For example, the aeration rate in a shake flask can be significantly affected by vessel geometry. A 250 mL flask with a wide neck can have roughly twice the aeration rate compared to a 250 mL narrow-neck flask. This shows that even small design changes can have a major impact on process performance.
David Brühlmann [00:25:07]:
This wraps up part one of our conversation so far. Tibor Anderlei has unpacked why small-scale experiments fail to translate, how mass transfer dynamics differ across platforms, and how oxygen transfer rate and CO₂ transfer rate monitoring reveal limitations that dissolved oxygen alone cannot capture. These are not just academic distinctions—they are the difference between a process that scales and one that doesn’t. In part two, we go deeper…
For additional bioprocessing tips, visit us at www.smartbiotechscientist.com. Stay tuned for more inspiring biotech insights in the next episode. Until then, let’s continue to smarten up biotech.
Disclaimer: This transcript was generated with the assistance of artificial intelligence. While efforts have been made to ensure accuracy, it may contain errors, omissions, or misinterpretations. The text has been lightly edited and optimized for readability and flow. Please do not rely on it as a verbatim record.
Book a free consultation to help you get started on any questions you may have about bioprocess development: https://bruehlmann-consulting.com/call
About Tibor Anderlei
Tibor Anderlei is a bioprocess technology expert with over 30 years of experience in small-scale cultivation systems. He specializes in orbital shaken bioreactors and scale-up strategies, supporting biopharma development from microtiter plates and shake flasks to stirred tank systems. His work bridges early-stage screening with industrial bioprocess implementation, with a focus on improving reproducibility and scale-up reliability.
At Kühner Shaker, he is focused on ensuring customer success and satisfaction through scientific and equipment solutions.
Connect with Tibor Anderlei on LinkedIn.
If you’re interested in this topic, check out these episodes on building a robust scale-up strategy. To get it right, you need to view the process from multiple angles—regulatory, digital, and operational.
Episode 03 - 04: How to Master Biotech Scale-up Without Guesswork with Leonardo Sibilio
Episode 25 - 26: 9 Critical Steps for a Seamless Transition to Large-Scale Production
Episode 231-232: From IND to BLA: The Biologics CMC Decisions That Determine Regulatory Success with Henri Kornmann
Episode 233-234: Why Most Bioprocess Automation Projects Fail with Anthony Catacchio
Episode 237-238: High-Throughput Microbial Screening with Sebastian Blum
Below, you’ll find a curated collection of resources, technical guides, and regulatory links shared by our guest.
David Brühlmann is a strategic advisor who helps C-level biotech leaders reduce development and manufacturing costs to make life-saving therapies accessible to more patients worldwide.
He is also a biotech technology innovation coach, technology transfer leader, and host of the Smart Biotech Scientist podcast—the go-to podcast for biotech scientists who want to master biopharma CMC development and biomanufacturing.
Hear It From The Horse’s Mouth
Want to listen to the full interview? Go to Smart Biotech Scientist Podcast.
Want to hear more? Do visit the podcast page and check out other episodes.
Do you wish to simplify your biologics drug development project? Contact Us
What if the difference between a seamless tech transfer and a costly setback isn't your process, but how you orchestrate the people and details behind the scenes?
In this episode of the Smart Biotech Scientist Podcast, David Brühlmann shares hard-earned lessons on the complexities of tech transfer and scale-up in the biotech industry.
In Part 1, you learned the six-pillar framework. Now I'm giving you the implementation playbook—starting with the human element that most people completely miss.
Story time. I was leading a tech transfer to a new manufacturing site. Everything was progressing—slowly, but progressing. Except for one guy in QC. Every interaction was difficult. Analysis requests were unpredictable. My team was stressed. His team seemed stressed. Walls were going up.
I was convinced he was the problem. Resistant to change. Maybe territorial about his lab.
Then I did something I should've done weeks earlier. I walked into his lab. No agenda. Just a conversation.
Turns out? He wasn't resistant. He was drowning. His lab was understaffed. His backlog was crushing. And every time we showed up with an "urgent" sample request, it threw his entire week into chaos.
He craved predictability. I was creating chaos.
Once I understood that, everything changed. We built a sampling calendar to give him a longer term view.
The transformation was immediate. Not because the science changed. Because I finally understood what he needed.
Here's the lesson: Understanding stakeholder needs is as critical as understanding the process.
Now, your stakeholder protocol.
1️⃣ First, map early. Identify every stakeholder: QC, QA, manufacturing ops, process development, regulatory, even facilities and IT if your process has special requirements.
2️⃣ Second, understand motivations. What does each stakeholder need? What are their fears? The QC manager might fear analytical backlogs. The QA manager might fear audit findings. The manufacturing supervisor might fear unproven procedures. Write it down.
3️⃣ Third, communication plan. Match frequency and method to stakeholder type. Some people want weekly written updates. Some want face-to-face check-ins every two weeks. Some just want to know you'll call them if there's a problem.
4️⃣ Fourth, use the Power-Interest Grid. Focus your energy on high-power, high-interest stakeholders. They're the ones who can kill your project or accelerate it.
5️⃣ Fifth, build trust face-to-face whenever possible. Especially for the resisters. Email doesn't build trust. Video calls are better than nothing. But nothing beats sitting in someone's space and listening.
Another story. We transferred a process to a new site. Identical equipment specs. Identical SOPs. We'd even sent people for hands-on training.
First batch at the new site? Completely different performance. Lower viability. Lower titer. Different impurity profile.
We spent months troubleshooting. Tested everything. Media? Same lot numbers. Seed train? Same frozen vials. Bioreactor control? Same setpoints. Environmental monitoring? All in spec.
Finally, after exhausting every rational explanation, someone noticed the obvious. Different light exposure.
We ran a controlled study. Light exposure was affecting the culture. Not enough to trigger an out-of-spec environmental reading. Enough to change cell behavior.
The lesson? List ALL differences upfront—and even then, expect surprises. Environmental factors matter. Light. Temperature fluctuations in the room. Vibration from nearby equipment. Document everything, even the "obvious" stuff.
Now, your mass transfer checklist.
Calculate scale-down ratios for key parameters. Mixing time increases with scale—you need to plan for that. Power per volume is typically kept constant. kLa—oxygen transfer—plan for a decrease. Impeller tip speed is a major consideration for shear-sensitive products.
Run scale-down models at the receiving site before you commit to full scale. This isn't optional. You need to prove the physics work in their equipment with their utilities.
And document everything. Not just the process parameters. The room temperature range. The water quality specs. The equipment maintenance history. The things that live in people's heads and never make it into batch records.
Decision framework time.
When to build internal? Platform technology you'll use repeatedly. If you're a monoclonal antibody company planning five programs over three years, in-house manufacturing starts making sense. Core competitive advantage in manufacturing—if your IP is in the process, not just the molecule, you might need to keep it in-house. Commercial volumes that justify capital investment. Or absolute control requirements over IP and process knowledge.
When to outsource? Novel modality with uncertain commercial potential. Need speed to clinic—CDMOs have infrastructure ready today. Limited capital for facility investment. Or strategic redundancy—testing multiple CDMOs so you're not dependent on a single partner.
Matthias Müllner gave us the insight: External CMC expertise bridges gaps early—build internal capability gradually. You don't need to decide everything day one. Start with outsourced. Learn what you actually need. Then selectively insource the pieces that create competitive advantage.
📅 Weeks 1 through 4: Foundation.
Define your Quality Target Product Profile and Critical Quality Attributes with the receiving site. Not at them. With them. Map the stakeholder landscape using the protocol we just covered. Create a detailed tech transfer plan document—this becomes your contract with yourself. And identify which parameters are scale-dependent versus scale-independent.
📅 Weeks 5 through 8: Risk Mitigation.
Conduct a gap assessment. Equipment, methods, training needs. Qualify raw materials at the receiving site—source, vendor approval, comparability. You cannot assume your supplier has the same qualification status at their site. Run scale-down models at the receiving site. Develop a comprehensive sampling plan with statistical power. Train receiving site personnel—and I don't mean train them on SOPs. Train them on the why. Why does this step matter? What happens if it goes wrong? What are the early warning signs?
And here's the critical one: Document tribal knowledge. Capture the undocumented tricks. The environmental nuances. The operator expertise that lives only in people's heads. The way your senior operator knows the culture is stressed before the dissolved oxygen trace shows it. Write that down.
📅 Weeks 9 through 12: Execution Preparation.
Co-author batch records with the receiving site. Not you write, they review. Co-author.
Establish communication protocols—who calls whom when something goes sideways? Define success criteria and go/no-go decision points. Plan for contingencies—if the scale-down model fails, what's plan B?
Go/no-go decision points. You don't proceed to full scale unless:
If any critical gap remains, you stop. You do not proceed to full scale hoping it'll work out. Hope is not a strategy.
Early in my career, I thought I needed to control everything. Write all the protocols. Review all the data. Draft all the reports.
Result? I became the bottleneck. Burned out. And paradoxically, progress slowed.
The turning point came when I got an assistant for admin and protocol and report writing. Suddenly, I had time for the things only I could do. Strategic decisions. Stakeholder relationships. Critical technical judgment calls.
The insight that changed everything: As a leader, focus on the 20% that only you can do. I further honed this as an entrepreneur. You have limited hours and limited attention span. If you spend them on the 80% that someone else could do, you're stealing from the 20% that creates actual value.
Your action item this week: Identify your 80% activities. Then plan to delegate them within 90 days. Not someday. Within 90 days.
You're staring at a tech transfer timeline. Leadership wants aggressive dates. The CDMO is confident but vague. And you're carrying the weight of knowing that if this slips, the entire program slips.
That pressure? It's real. The complexity? Also real.
But here's what's also real. Tech transfer isn't magic. It's not an art. It's building on six essential pillars with discipline and foresight.
You've got the framework now. Technical process understanding—know what's scale-dependent. Analytical comparability—design it upfront. Quality by Design—define your CQAs before the crisis. Stakeholder management—understand what people need. Partner selection—choose the CDMO that challenges you. Strategic build versus buy—focus on competitive advantage.
You've got the 12-week protocol. Foundation, risk mitigation, execution preparation.
And you've got the mindset shift. Master the human element. Understand the physics. Plan systematically. Delegate the 80% that doesn't require your unique expertise.
Your "piece of cake" tech transfer? It can actually be cake. Not because tech transfer got easier. Because you got better at orchestrating complexity.
The timeline's not going to get less aggressive. The stakeholders aren't going to get less demanding. But you now have a system that works regardless.
Go make it happen.
If you liked today’s conversation about scale-up and tech transfer, please tell us by leaving a review. Your review helps scientists like you discover these resources.
For additional bioprocessing tips, visit us at www.smartbiotechscientist.com. Stay tuned for more inspiring biotech insights in the next episode. Until then, let’s continue to smarten up biotech.
Disclaimer: This transcript was generated with the assistance of artificial intelligence. While efforts have been made to ensure accuracy, it may contain errors, omissions, or misinterpretations. The text has been lightly edited and optimized for readability and flow. Please do not rely on it as a verbatim record.
Book a free consultation to help you get started on any questions you may have about bioprocess development: https://bruehlmann-consulting.com/call
If you’re interested in the ideas discussed, here are some of the guests David referenced in this episode.
Episodes 91 - 92: Mass Transfer Secrets: Mastering Bubbles and kLa from Bench to Large-Scale Production with Lars Puiman & Rik Volger
Episodes 79 - 80: Think Before You Build: Holistic Approaches to Biotech Facility Design with Alfredo Martínez Mogarra
Episodes 57 - 58: Crafting a Solid CMC Strategy: Key Factors and Common Pitfalls with Matthias Müllner
Episodes 23 - 24: Strategies for Success: Master CMC Development with Gene Lee
David Brühlmann is a strategic advisor who helps C-level biotech leaders reduce development and manufacturing costs to make life-saving therapies accessible to more patients worldwide.
He is also a biotech technology innovation coach, technology transfer leader, and host of the Smart Biotech Scientist podcast—the go-to podcast for biotech scientists who want to master biopharma CMC development and biomanufacturing.
Hear It From The Horse’s Mouth
Want to listen to the full interview? Go to Smart Biotech Scientist Podcast.
Want to hear more? Do visit the podcast page and check out other episodes.
Do you wish to simplify your biologics drug development project? Contact Us
Tech transfer in biotech can feel like a high-stakes gamble, balancing regulatory shifts, incomplete data, and mounting stakeholder pressure—all with timelines breathing down your neck.
In this episode of the Smart Biotech Scientist Podcast, David Brühlmann shares hard-earned lessons on the complexities of tech transfer and scale-up in the biotech industry.
Our process development head leaned back in his chair and smiled. "Guys, I have a quick tech transfer to our existing facility. Piece of cake."
Those were his exact words. And I believed him. Why wouldn't I? We had the process nailed. The timeline was tight but doable. The receiving site had done this before.
Except here's what nobody told me: regulatory requirements had evolved. Our process documentation was Swiss cheese. And what I thought was a robust process? It was a house of cards held together by undocumented operator tricks.
Maybe you're staring at a similar situation right now. Timeline pressure mounting. Stakeholders asking for updates you can't confidently give. That nagging feeling that there's something critical you're missing.
You're not wrong to feel that way.
Today, I'm giving you the framework that could've saved our team months of delays and millions in costs. The six-pillar approach that turns tech transfer from a gamble into a managed process.
Here's what we're covering. First, the six essential pillars in every tech transfer—and why missing just one of them puts your project at risk. Second, the technical essentials, specifically why mass transfer physics change everything at scale. Third, the stakeholder strategy that turns resistance into genuine partnership. Fourth, when to build internal capability versus outsource—the decision framework nobody teaches you in grad school. And fifth, real implementation: your 12-week tech transfer preparation protocol.
FDA data shows that over 40% of CMC-related IND issues trace back to manufacturing problems. Not formulation. Not analytics. Manufacturing. And here's the thing—tech transfer is now the number one CDMO differentiation factor. Lonza's data projects that by 2029, 56% of all biologics will be manufactured by CDMOs.
The hidden cost? Poor tech transfer doesn't just delay your program. It questions comparability. It my lead to expensive bridging studies. It hands your competitor the market window you were counting on.
But here's your opportunity. Master this, and you compress timelines while everyone else scrambles to put out fires. You become the person leadership trusts with the critical path.
So let's talk about the six pillars.
Here's the physics challenge you need to tackle. What works brilliantly at 2 liters can fail spectacularly at 2,000 liters. Not because you did something wrong. Because physics changes.
Mass transfer is the big one. Specifically, kLa—oxygen transfer coefficient. Lars Puiman and Rik Volger explained this well on the podcast. Bubble size changes with scale. Residence time changes. Mixing patterns change.
Here's a concrete example. Your 2-liter benchtop bioreactor might have a kLa of 15 to 25 per hour. Your 2000-liter production vessel? You're looking at 8 to 15 per hour. That's roughly a 40 to 60% reduction in oxygen transfer efficiency—and if you're not planning for it, your high-density fed-batch is going to underperform at scale.
Now think about what that means for a high-density fed-batch culture. If your cells are oxygen-limited at production scale but not at bench scale, you're going to see different growth profiles. Different metabolite accumulation. Different product quality.
Your action item here is straightforward but not easy. Map every critical process parameter and ask: is this scale-dependent or scale-independent? Temperature setpoint? Scale-independent. Mixing time? Very scale-dependent. Impeller tip speed? Scale-dependent. pH control strategy? Depends on your system. Can your large-scale bioreactor system supply the oxygen your cell line needs?
Make that list before you commit to a tech transfer timeline.
Here's the blind spot I’ve seen. Teams obsess over the process—feed rates, temperature profiles, aeration strategy. And they completely neglect the sampling plan.
Let me be direct. Analytics isn't separate from tech transfer. It IS tech transfer.
Think about it. How do you prove your process transferred successfully? You measure it. And if your analytical methods aren't validated at the receiving site, or if your sampling plan doesn't have statistical power, you're building conclusions on quicksand.
What you need is side-by-side comparability with real rigor. Full product characterization panel for the final product. And forced degradation studies to demonstrate that your comparability holds up under stress.
This is where most tech transfers actually fail. Not because the process drifted. Because nobody designed a sampling strategy robust enough to detect when it drifted.
Gene Lee said something on the podcast that should be tattooed on every CMC scientist's forehead: "Start CMC planning early—you can't retrofit smart strategy."
Here's the Quality by Design chain: Quality Target Product Profile flows to Critical Quality Attributes, which flow to Critical Process Parameters. If you don't know what quality means for your pr oduct, you literally cannot transfer the process. Because you don't know what to measure and you don't know what to control.
The mistake I see repeatedly? Teams hoping the CDMO will figure it out. They ship over a process description and some batch records and say, "Make it work."
That's not a tech transfer. That's a wish.
Your CDMO will execute your plan. If you don't provide one, they'll improvise. And their improvisation might be scientifically sound and completely wrong for your regulatory strategy.
Define your CQAs before tech transfer. Not during the crisis call after the first batch fails.
I'm going to tell you about the QC guy who taught me the most important tech transfer lesson of my career. And it had absolutely nothing to do with science.
But that's coming in Part 2. Stay tuned for what derails many projects: stakeholder management.
CDMO reality check. Your CDMO partner has deep expertise. They've scaled up hundreds of processes. But they execute YOUR plan.
If you don't have a plan, they will improvise. And that improvisation might be brilliant. It also might be completely misaligned with your regulatory strategy, your competitive timeline, or your quality requirements.
Selection criteria matter more than most people realize. According to Lonza, technology transfer capabilities have become a critical differentiator for successful partnerships and risk mitigation. Technical capability is table stakes. But you also need regulatory track record—have they filed INDs in your modality? And cultural fit—do they ask hard questions, or do they promise "no problem" to everything?
That second one is actually a red flag. The CDMO that promises smooth sailing without probing your process understanding? They're either overconfident or they don't care enough to push back.
You want the partner who challenges your assumptions early. Not the one who surfaces problems after you've committed three months and half a million dollars.
Alfredo Martínez gave us the principle: Think holistically before building—infrastructure is expensive.
And not just expensive in capital. Expensive in time. Expensive in opportunity cost. Expensive in the expertise you need to hire and retain.
I'll give you the full decision framework in Part 2. But here's the preview question: Are you building core competitive advantage or are you building commodity infrastructure?
Because if it's commodity infrastructure, somebody else has already built it better and cheaper.
That's the framework. Six pillars that most people never think about systematically. But knowing the pillars isn't enough. You need the playbook.
Thank you for listening to Part 1. In Part 2, I'm walking you through real implementation: the QC conflict story that changed how I think about stakeholders, the light exposure discovery that taught me to document everything, your 12-week preparation protocol with go/no-go gates, and the build-versus-outsource decision matrix.
If you liked today’s conversation about scale-up and tech transfer, please tell us by leaving a review. Your review helps scientists like you discover these resources.
For additional bioprocessing tips, visit us at www.smartbiotechscientist.com. Stay tuned for more inspiring biotech insights in the next episode. Until then, let’s continue to smarten up biotech.
Disclaimer: This transcript was generated with the assistance of artificial intelligence. While efforts have been made to ensure accuracy, it may contain errors, omissions, or misinterpretations. The text has been lightly edited and optimized for readability and flow. Please do not rely on it as a verbatim record.
Book a free consultation to help you get started on any questions you may have about bioprocess development: https://bruehlmann-consulting.com/call
If you’re interested in the ideas discussed, here are some of the guests David referenced in this episode.
Episodes 91 - 92: Mass Transfer Secrets: Mastering Bubbles and kLa from Bench to Large-Scale Production with Lars Puiman & Rik Volger
Episodes 79 - 80: Think Before You Build: Holistic Approaches to Biotech Facility Design with Alfredo Martínez Mogarra
Episodes 57 - 58: Crafting a Solid CMC Strategy: Key Factors and Common Pitfalls with Matthias Müllner
Episodes 23 - 24: Strategies for Success: Master CMC Development with Gene Lee
David Brühlmann is a strategic advisor who helps C-level biotech leaders reduce development and manufacturing costs to make life-saving therapies accessible to more patients worldwide.
He is also a biotech technology innovation coach, technology transfer leader, and host of the Smart Biotech Scientist podcast—the go-to podcast for biotech scientists who want to master biopharma CMC development and biomanufacturing.
Hear It From The Horse’s Mouth
Want to listen to the full interview? Go to Smart Biotech Scientist Podcast.
Want to hear more? Do visit the podcast page and check out other episodes.
Do you wish to simplify your biologics drug development project? Contact Us
What if the solution to cell therapy’s biggest cold-chain challenge comes from the biology of Arctic fish?
Cryopreservation is the linchpin of cell and gene therapy logistics—and for years, dimethyl sulfoxide (DMSO) has been the industry’s reluctant standard. DMSO keeps cells alive in the freezer, but at a cost: regulatory headaches, damaged cells, patient side effects, and complicated workflows. So what if an antifreeze-inspired innovation could finally retire DMSO for good?
This conversation features Steve Oh, a leader in advanced bioprocessing, whose career has placed him at the intersection of stem cell biology, process engineering, and clinical translation. Steve Oh joins David Brühlmann to share how a next-generation cryopreservation solution drawing from nature’s antifreeze proteins—lets cells survive, thrive, and simplify manufacturing from the bench to the clinic.
It is really a simple plug-and-play solution. It's been made to GMP grade. It has a Drug Master File. So it's simply just getting a bottle and then using it at the same concentration as you would currently use with DMSO at 5% or 10%. So most cells would just transition from DMSO to the solution without any problem.
David Brühlmann [00:00:23]:
Arctic fish survive in waters that would freeze most life solid. That biological insight, translated into synthetic peptide chemistry, may be exactly what cell therapy manufacturing has been waiting for. In part 1, Steve Oh walked us through the DMSO problem in depth: the toxicity, the cellular damage, the regulatory pressure. Now we get to solutions: from cryopreservation performance data to manufacturing logistics to what a transition actually requires. This is where it gets practical.
Can you give us some examples, Steve, of how this innovative approach helps cells survive better and maintain their viability and function?
Steve Oh [00:02:23]:
We have a presentation on various cell types, both T cells and MSCs. So we have an example where fresh pan-T cells isolated from donor apheresis were stored at 10 million cells per mL, and then they were frozen down for 40 days with the XT5 solution. And post-recovery, they were able to proliferate as well as the fresh product.
Another example was when we preserved T cells from two CDMO partners. The XT-Thrive® frozen product had almost equivalent—about 80%—secretion of IL-2, similar to fresh cells, whereas the DMSO-containing product was around 60%. And in terms of the immunophenotype, they expressed CD4/CD8 markers.
In terms of cytotoxic function, four DMSO-containing competitor products were tested against the XT-TRI solution at effector-to-target ratios of 1:1 and 0.3:1. So XT-Thrive® had the best performance in terms of cell-killing function over the other three DMSO-containing products. In fact, one product had no killing efficacy at all at the lowest effector-to-target ratio.
A third example is when CD4 and CD8 T cells were frozen for 7 days and then thawed, and nucleofection of the CAR-T gene was performed. The efficacy was about 80% for XT-Thrive® versus 60% for the CryoStor CS10 cryopreservation solution. These are the T-cell examples, where we’ve seen much better performance than CS10.
In terms of MSCs, we looked at holding the cells in solution for 24 hours prior to freezing. We found that the viability of the cells held in XT-Thrive® remained at about 90%, but DMSO dropped progressively—within 4 hours to 85%, and then overnight down to 60%.
Then when we froze and thawed them, recovery of viability was about 90% for XT-Thrive® and about 85% for CryoStor CS10, and it continued to drop to about 60% over 8 hours, whereas XT-Thrive® was maintained around 90% in MSC cultures.
All these experiments were done under both serum-containing and serum-free conditions. Many products are moving toward defined serum-free conditions, and cells tend to be more sensitive without the serum background. So we've seen this performance to be consistent irrespective of serum-free or serum-containing conditions.
And finally, when we put these cells back into culture on microcarriers—which is a scalable method for cell production—we saw immediate recovery and growth of the cultures post-thaw with XT-Thrive®. But with DMSO, there was a 4-day lag followed by only marginal growth. So overall, we observed about a 2.5-fold increase in cell yield post-thaw.
David Brühlmann [00:05:20]:
To what extent, Steve, were these stark differences between XT-Thrive® and DMSO due to ice crystal formation and differences, I'd say, in mechanism?
Steve Oh [00:05:32]:
I think that is the key benefit of this approach. We have seen in microscopic studies that ice crystals are relatively large in water, and with both antifreeze proteins and the XT-Thrive® product, the crystal size is reduced to about 10–50% of that seen in water. So most of the damage actually occurs during thawing, when these crystals can cause mechanical damage to the cell membrane if thawing is not rapid enough.
David Brühlmann [00:06:01]:
Let's shift gears here, Steve. So we have seen the stark differences between DMSO and this novel solution. We have also talked about the main challenges linked to DMSO. Now, another question we need to tackle is: we have a new product that seems to work well, but how does this affect established workflows—washing, freezing and thawing, temperature? Can you give us a picture there? What changes for the person doing the work in the lab?
Steve Oh [00:06:33]:
So one of the first things we did was to run a hold-time experiment over 24 hours. We learned in the early days that once you put cells in DMSO, you have to process them quickly—within 4 hours, but ideally between 30 minutes to 2 hours.
That’s fine when you're using small vials of cells that you can aliquot at 1 mL each. But once you're processing, say, 100 mL bags—or even a 1 L batch that you then aliquot into 100 mL bags—that workflow becomes very rushed.
So that's why we did the real-time hold experiment over 24 hours, to ensure that cells could be processed over a full day and to assess whether viability would be affected. And sure enough, we found that viability was maintained over the 24 hours, which makes processing much more convenient.
On the backend, there were also tests where the solution was injected into animals at 100× the concentration used for cryopreservation, and there was no toxicity observed. So there isn’t the same requirement to wash away the DMSO-containing solution—you could inject it as is post-thaw. It behaves almost like water—not exactly, but it is essentially non-toxic.
So you can inject it into the patient without that extra wash step. Again, this reduces the risk of contamination due to manual washing and centrifugation steps, and significantly simplifies the workflow from both a manufacturing and point-of-care delivery perspective.
David Brühlmann [00:08:01]:
How does this simplified workflow without an additional wash step after thawing affect—or facilitate—the distribution of these therapies to remote locations? Because that's one of the challenges we are still facing in cell and gene therapy: how do we bring these therapies from the manufacturing site—whether it's a hospital or a company—to the patient?
Steve Oh [00:08:27]:
So we have tested the solutions at 4°C, −80°C, and −196°C. Across all these temperatures, cell viability and performance are as good as or better than with DMSO. So in autologous therapy, you can hold the cells at 4°C for as long as needed for transportation. In manufacturing, you can create master cell banks and working cell banks at −80°C to −196°C. And for allogeneic therapy, you can handle much larger volumes, enable long-term preservation over years, and then thaw the cells for localized treatment.
One of the benefits of being able to operate at 4°C is that, as I’ll mention later, you can transport certain cell types—like organoids or even organs—for 3 to 5 days at cold temperatures without freezing. So they never form ice crystals. You can transport them across the country, and the organs are still functional after warming. So again, it highlights the versatility of the solution compared to DMSO.
David Brühlmann [00:09:39]:
So am I hearing correctly that this product cannot only be used for single cells, but for organoids and potentially even in tissue engineering or some other areas?
Steve Oh [00:09:50]:
Yeah, that's right. We don't have published data yet, but there is accumulated evidence that heart islets are functioning in XT-Thrive®, and the XT -Novo data for larger human organs will be coming up. So at ISCT, in May 2026 in Dublin, we should have more data on these different cell types, including organoids.
And organoids have their own challenges because they are fairly large structures—up to 5–10 millimeters in size—and they need to be kept cold or produced fresh because there’s traditionally no good way to freeze them down or hold them at cold temperatures. And we think we have some good data to show for that.
David Brühlmann [00:10:31]:
Let's assume that my team and I have developed a T-cell process using DMSO, and now I'm listening to this podcast and I learn about this much better product to freeze and thaw cells. How easily can I switch over to this new product?
Steve Oh [00:10:49]:
I think it is really a simple plug-and-play solution. It's been made to GMP grade. It has Drug Master Files. So it's simply just getting a bottle and then using it at the same concentration as you would currently use with DMSO at 5% or 10%. So most cells would just transition from DMSO to the solution without any problem.
In terms of the manufacturing facilities, there are sites in San Francisco and Vienna, and clients are welcome to visit them to audit the manufacturing process. We are also talking to some major distributors in the US and Japan to extend the global reach.
David Brühlmann [00:11:28]:
Let's zoom out and look at the broader cell and gene therapy picture. There's a lot of innovation happening. Beyond DMSO, what are some impactful areas you're seeing or some promising areas that you think are worthwhile highlighting?
Steve Oh [00:11:48]:
Related to cryopreservation or beyond cryopreservation?
David Brühlmann [00:11:51]:
In general, beyond cryopreservation.
Steve Oh [00:11:54]:
I think the biggest challenge with stem cell–based therapies is the long differentiation time from the starting material to the final product. That's one challenge.
The second is maintaining the consistency and purity of the target population, whether it be neural stem cells for Parkinson’s disease trials or cardiomyocytes for heart disease. So this remains an ongoing challenge.
The third challenge is achieving this at a low cost of goods. Process optimization is key here, just as in biologics manufacturing, because many protocols rely on numerous combinations of growth factors and small molecules to generate the final cell type over many weeks.
So I think the cost of goods, due to the complexity of the process, will determine whether we achieve widespread adoption of these cell therapies.
David Brühlmann [00:12:43]:
What technology innovations have you seen that you think could solve one of these challenges?
Steve Oh [00:12:50]:
I have seen some data from a company called Accelerated Biosciences, using a source of cells called trophoblast stem cells. They had data showing that with a one-day induction, they could produce a cell type that secretes dopamine. And when injected into mouse models of Parkinson’s disease, they were able to recover function.
But that company has been facing challenges raising funds to move into a Phase 1 clinical trial. So if a transformative technology like that can generate a functional cell type—similar to a dopaminergic neuron—in just one day, that would be fantastic in terms of process efficiency, manufacturing, and cost of goods. But it has not yet reached Phase 1 clinical trials.
David Brühlmann [00:13:34]:
Such an innovation would move the needle forward, but it's a pity to see disruptive technology stall because of a lack of funding. I mean, it looks very promising. Even later, perhaps you might run into some technical issues—who knows—but it is at least worthwhile pursuing the development and seeing whether it will work in a commercial setting.
Steve Oh [00:13:58]:
If you had the opportunity, it might be good to get a venture capitalist or someone from the investment side who can talk about what needs to be addressed to unlock funding.
David Brühlmann [00:14:08]:
Yeah, absolutely. And if one of the venture capitalists is listening, this is an opportunity. We are in the money game, yes, but I think we should also have a broader perspective. That's at least my personal view of the industry.
We should pursue technologies that don’t have an immediate return on investment because, at the end of the day, we’re in it to treat patients. So I think this is something that, if I may say, our industry could further develop—the social dimension of innovation—not only the immediate ROI.
Well, this has been great, Steve. Before we wrap up, what burning question haven't I asked that you are eager to share with our biotech community?
Steve Oh [00:14:52]:
I think in terms of disruptive technology, XT-Thrive®, this single cryopreservation solution, will contribute significantly to cell-based therapies because it has zero toxicity. It preserves cells and tissues in a much better state than traditional DMSO across many different cell types. Recovery of cells post-storage is much higher—more viable, functional, and healthier.
It doesn't need a wash step, and it doesn't cause irritation or edema at the site of injection, which makes it easier to administer to patients. So I think this will be one of the key solutions in cell therapies, impacting both current T-cell–based therapies and future stem cell therapies. Thank you for the opportunity to speak about this topic.
David Brühlmann [00:15:38]:
Absolutely. It's a pleasure. And if there is only one thing you want our listeners to walk away with, what would it be?
Steve Oh [00:15:46]:
If you're looking for a cryopreservation solution, just reach out.
David Brühlmann [00:15:59]:
Okay. So this leads me to the final question, Steve. Where can people get ahold of you and this product?
Steve Oh [00:16:05]:
So I'm on LinkedIn, and my email—if you can share it—is skwoh.so@gmail.com.
David Brühlmann [00:16:15]:
There you have it, Smart Biotech Scientists. You will find the link in the show notes. Reach out to Steve and his team. And thank you, Steve, so much for being on the show today and sharing both the challenges and solutions in cryopreservation.
Steve Oh [00:16:30]:
Thank you so much. Thanks, David.
David Brühlmann [00:16:34]:
From Arctic antifreeze proteins to clinical-grade cryopreservation, Steve Oh has shown us that the DMSO era may finally have a credible successor. The performance data is compelling, and the manufacturing implications are significant. If you're navigating these challenges in your own program, I hope this conversation gave you a clearer path forward.
And if it did, please take a moment to leave a review on Apple Podcasts or your favorite platform and share it with a colleague. For additional bioprocessing tips, visit www.smartbiotechscientist.com. Stay tuned for more inspiring biotech insights in our next episode. Until then, let's continue to smarten up biotech.
Disclaimer: This transcript was generated with the assistance of artificial intelligence. While efforts have been made to ensure accuracy, it may contain errors, omissions, or misinterpretations. The text has been lightly edited and optimized for readability and flow. Please do not rely on it as a verbatim record.
Book a free consultation to help you get started on any questions you may have about bioprocess development: https://bruehlmann-consulting.com/call
About Steve Oh
Steve Oh is a seasoned biotech scientist and advisor with a career defined by innovation and resilience. After more than two decades at A*STAR’s Bioprocessing Technology Institute, where he developed cutting-edge stem cell and bioprocessing technologies, he transitioned into entrepreneurship and advisory roles across the global biotech ecosystem.
Despite early challenges in launching spin-off ventures, he leveraged those experiences to guide companies in areas such as viral vector manufacturing, cultured meat, and advanced cell therapies. He continues to shape the future of biotechnology through research collaborations, advisory work, and mentorship.
Connect with Steve Oh on LinkedIn.
If you’re interested in this topic, check out these episodes, where we explore how Minnesota’s frozen forests inspired a new wave of biotech innovation, transforming how life-saving cells are frozen, stored, and shipped.
Episodes 161 - 162: How to Achieve 85%+ Cell Recovery Without DMSO's Toxic Side Effects with Jeffrey Allen
This is Steve’s second appearance on the podcast. You can also catch his earlier conversation with David, where they explored the challenges and opportunities of cell and gene therapy.
Episodes 11 - 12: From Lab to Patient: Steve Oh’s Guide to Mastering Cell Therapy Process Development.
David Brühlmann is a strategic advisor who helps C-level biotech leaders reduce development and manufacturing costs to make life-saving therapies accessible to more patients worldwide.
He is also a biotech technology innovation coach, technology transfer leader, and host of the Smart Biotech Scientist podcast—the go-to podcast for biotech scientists who want to master biopharma CMC development and biomanufacturing.
Hear It From The Horse’s Mouth
Want to listen to the full interview? Go to Smart Biotech Scientist Podcast.
Want to hear more? Do visit the podcast page and check out other episodes.
Do you wish to simplify your biologics drug development project? Contact Us
Sixty years after its arrival, one molecule still dominates cell cryopreservation: DMSO. It’s unmatched in its ability to get cells through the freeze–thaw cycle alive, and its clinical track record is extensive. Yet beneath the surface of every viable vial lurk toxicity risks and a legacy of side effects that have regulators and innovators hungry for change.
Why hasn’t DMSO been dethroned—and what’s finally threatening its reign?
Joining David Brühlmann is Steve Oh, whose 22 years at Singapore’s A*STAR produced 43 patents, breakthroughs in stem cell microcarrier technologies, and hard-won expertise on the toughest bottlenecks in bioprocessing. Steve Oh isn’t just theorizing about better cryoprotectants—he’s lived the old problems and is now advising startup trailblazers trying to solve them for good.
DMSO has been the gold standard because of its unique chemical properties and extensive clinical track record, making it difficult to fully replace. But that's a 60-year-old product, and a lot of things have changed since then. So some of the properties are as follows: physicochemical efficiency. It has rapid membrane permeability, and it enters the cells and equilibrates with the intracellular environment faster than other penetrating agents like glycerol. Water displacement: it forms hydrogen bonds with water about 30% stronger than between water molecules themselves, thereby preventing the formation of intracellular ice crystals.
David Brühlmann [00:00:42]:
For 60 years, one molecule has defined cell cryopreservation—effective enough to become the universal standard, yet problematic enough that the FDA attempted to ban it twice. My guest today, Steve Oh, spent 22 years at Singapore's A*STAR, invented stem cell microcarrier technologies, CRISPR activation, and a lot more. He holds 43 patents and has seen this problem from every angle. Steve brings hard-won wisdom to one of bioprocessing’s most persistent challenges. Why has DMSO survived this long, and what finally threatens its reign? Let's find out!
Welcome, Steve. It's good to have you on today.
Steve Oh [00:02:50]:
Thank you, David, for the invitation.
David Brühlmann [00:02:52]:
Steve, share something that you believe about bioprocess development that has made the most impact.
Steve Oh [00:02:59]:
Okay, love to. I think there are 3 that I can think of right now. The development of the AMBR system for small-scale volume optimization that has made a lot of impact in the biologics industry. The development of high-intensity perfusion cultures that has reduced the volume and the footprint of bioreactors for generating high titers of proteins, recombinant antibodies. And I think one that's coming in the future is the use of digital twins to reduce the number of experiments and then focus on the key experiments. I believe you're going to be talking about that in the future, right?
David Brühlmann [00:03:38]:
Yes, absolutely. And we have already covered this topic—digital twins and hybrid modeling—a few times on previous episodes. So if you're interested in that, Smart Biotech Scientists, go back and listen to these episodes. It's a huge pleasure to have you back on, Steve. For those listeners who have not had a chance to listen to our interview we did, I think a couple of years back, take us back to the beginning. What sparked your passion for biotech and cell therapy, and what pivotal moments during your long career shaped your path to becoming a leader in stem cell bioprocessing solutions?
Steve Oh [00:04:17]:
I think back in the '90s, when the production of antibodies was challenging, I had the opportunity to complete my PhD and get into learning about the use of bioreactors for manufacturing cells, which at that time was a big challenge. People were doing bacterial fermentation but not animal cells. So that was the first pivotal moment that gave me the training and the opportunity to get into this field.
And then around 2001, post the discovery of pluripotent embryonic stem cells, again that was a challenge—how to produce stem cells at scale in bioreactors. We built a small team to look at growing these cells, which were very dependent on support cells—feeder cells—and Matrigel, all kind of undefined conditions. And finally, we found a way to switch them to grow on microcarriers in bioreactors. So those were the two big opportunities I had to make an impact in bioprocessing and come up with new solutions to scale.
David Brühlmann [00:05:22]:
And what were some pivotal moments you experienced during your long years at A*STAR that finally led you to also take a leap and pursue entrepreneurial endeavors?
Steve Oh [00:05:32]:
After the discovery of microcarriers for manufacturing stem cells, I did try my hand at forming a spin-off company, but the challenge was raising cash to build a CDMO-type business model and then finding a CEO. So my entrepreneurial skills were not that strong, and we didn't succeed. I'm glad to see that there are companies out there now that are able to make that impact. Still, no products made from bioreactors yet, but people are trying.
David Brühlmann [00:06:03]:
Wow, that's fantastic. You hold a lot of patents—exactly, if I'm not mistaken, 43 patents across microcarrier technologies, serum-free media, and CRISPR activation. So you could have focused on many different areas. What drew you to cryopreservation as one of your key advisory roles? And tell us also what made you believe that this was an area ripe for innovation.
Steve Oh [00:06:31]:
It was in collaboration with a company called X-Therma back in 2015, I believe—or maybe a bit later—where I saw that they had this amazing solution that could transport whole hearts across the country over 3 days. And we had seen there were challenges with DMSO for cryopreservation of pluripotent stem cells and the first challenging differentiated cell type—neural stem cells. So I approached the CEO, Xiaoxi, and looked at potentially testing out that solution for stem cell applications. And I realized that in the final cell therapy, you wouldn't be giving fresh cells—you'd have to freeze them down and use the thawed cells for patient injection.
So we needed something that would be robust and give potent cell properties as close to fresh cells as possible. And really, nobody at that time was looking at the replacement of DMSO, the standard solution. So that's why I felt that there was a blue ocean opportunity to collaborate with them. And then once I left A*STAR about 4 years ago, I sought the opportunity to be a scientific advisor. That's why I'm working with X-Therma on educating the field in alternatives to DMSO.
David Brühlmann [00:07:48]:
Let's start with the fundamentals, Steve, because cryopreservation—or shall I say the preservation of cells—is a big, big topic, not only in cell therapy, but I'd say in various areas of biologics. Help our listeners understand what are the main challenges scientists face when preserving cells, freezing cells, and why has DMSO remained the gold standard despite its limitations for many decades?
Steve Oh [00:08:17]:
So DMSO has been the gold standard because of its unique chemical properties and extensive clinical track record, making it difficult to fully replace. But that's a 60-year-old product, and a lot of things have changed since then. So some of the properties are as follows: physicochemical efficiency. It has rapid membrane permeability, and it enters the cells and equilibrates with the intracellular environment faster than other penetrating agents like glycerol.
Water displacement: it forms hydrogen bonds with water that are about 30% stronger than between water molecules themselves, thereby preventing the formation of intracellular ice crystals. It's versatile. In the pre-cell therapy days, hematopoietic stem cells (HSCs) were mostly the cell type used in cryopreservation—blood products, some immune cells, and mesenchymal stromal cells (MSCs).
And the HSCs have been used in clinical and regulatory environments—so lots of stem cell transplants. Its side effects are documented and manageable within existing medical protocols, such as maximum daily dose limits, typically 1 gram per kilogram of patient weight. There are standardized protocols and workflows built around the 5–10% DMSO formulation. Transitioning to alternatives requires extensive and costly validation to ensure that therapeutic efficacy is not affected.
Then the practical and economic advantages include low cost, high stability, long shelf life at low temperatures, and wide availability in high-purity grades—such as United States Pharmacopeia (USP) grade for clinical use. And it's easy to use in controlled-rate freezers at about −1°C per minute, so fairly simple to implement. So that's the reason why it has been in use for 60 years.
David Brühlmann [00:10:14]:
What I'm hearing here, Steve, is that DMSO has a lot of advantages, and that's the reason why it has been used for so long. Isn't it interesting that the FDA has tried to ban DMSO twice? So what are the specific issues with the toxicity of DMSO, and what are some other aspects that make its use problematic?
Steve Oh [00:10:39]:
One example was back in 1965—there was a ban on human testing because of safety alarms regarding lens (eye) toxicity in animals, and then a sudden death of an Irish woman after topical use. So these early concerns established regulatory wariness that persists today.
Now, for modern cell therapies, there are new issues that we've never had—the challenges of the variety of cell types now being used. This includes cellular dysfunction and loss of potency. For T cells, at concentrations as low as 0.25–1%, DMSO inhibits CD4-positive T cell activation, proliferation, and cytokine production such as IL-2, IL-4, and IL-17A. It downregulates genes in early signaling and T-cell receptor pathways.
Then for NK cells, DMSO is associated with altered expression of natural killer cell markers and diminished effector functions. For stem cells, DMSO is known as a differentiation inducer, so it can downregulate pluripotency factors like OCT4 and NANOG at concentrations as low as 0.125%, potentially biasing their therapeutic identity before they reach the patient.
In terms of physical and structural damage, DMSO induces pore formation in cell membranes and can disrupt the cytoskeleton by dehydrating lipids and interacting with proteins. In terms of mitochondrial and metabolic stress, it can compromise mitochondrial respiration, induce oxidative stress, and trigger apoptosis through caspase-9 and caspase-3 activation.
And then in patients, DMSO toxicity significantly increases dose-dependent cell damage and adverse reactions. Clinical risks include cardiovascular issues, severe nausea, neurological symptoms, and allergic reactions, which necessitate rapid removal or lower concentrations.
David Brühlmann [00:12:42]:
Let me reframe this because you're making an excellent point here, Steve. I have worked in biologics for most of my career, and DMSO is used to freeze cell banks. And pretty much the only parameter many teams were interested in is viability when you thaw your cells.
But now what I'm hearing is that in cell therapy, we are playing a completely different ball game. Because we're not just cultivating cells in a bioreactor—we are using these cells to treat patients. So we have to look much more carefully at what's going on at the genetic level, at the transcriptomics level, and at the metabolic level. So we have a plethora of aspects to watch out for.
Steve Oh [00:13:28]:
Correct. Because the cells are the functional entities, just having viable cells is not sufficient. You have to have the cells be able to perform the function that they were intended for, as they would when fresh.
David Brühlmann [00:13:40]:
Can we look into the cells a bit? What's happening when you're using DMSO and you're freezing and then thawing the cells? What exactly happens at the microscopic level? What are these changes that affect the genetic stability, the transcriptomics, or the metabolism of these cells?
Steve Oh [00:14:01]:
Some of the toxicity issues in cryopreservation are that when cells are exposed to DMSO at temperatures above 4°C during thawing, it can disrupt the cellular membrane, cause mitochondrial damage, and lead to the production of reactive oxygen species. So this is cumulative, and it can start to create all those metabolic damages that I mentioned earlier.
On top of that, exposure to DMSO can lead to undesirable phenotypic changes in stem cells due to alterations in DNA methylation and histone-modifying enzymes that can open up the DNA for priming towards differentiation or close it down such that they can't differentiate.
Then there is the time- and dose-dependent risk. Toxicity is directly related to concentration and exposure time. Typically, DMSO is used in the 5–10% range, but even up to 40% DMSO has been used, and this completely destroys hematopoietic stem cell viability. And then, as I mentioned earlier, when residual DMSO is infused into patients, you can have nausea, vomiting, cardiovascular events like bradycardia and arrhythmia, neurological symptoms like seizures and dizziness, and allergic reactions.
And finally, in terms of manipulating the DMSO itself, because of these toxicity issues, it needs to be washed away to remove residuals and reduce the overall volume to decrease the dose. This can lead to potential opportunities for contamination of the product by having to do this additional step.
David Brühlmann [00:15:38]:
To what extent can these detrimental effects happen even though the viability looks okay?
Steve Oh [00:15:46]:
So even at low concentrations post-wash, the types of disruptions that can happen are as follows: Alterations in DNA methylation: DMSO disrupts the balance between the “writers” and “erasers” of DNA methylation, leading to widespread genomic instability.
The major risk in preserving stem cells and related products is that we don’t fully understand how these methylation changes will affect the long-term behavior of the cell product.
David Brühlmann [00:16:48]:
Given what we've discussed so far, Steve, what are the options we have at our disposal as scientists? Because we could use DMSO, but there are some detrimental effects you just mentioned, and we have to be aware of that. And there are now some alternative products. So what are these products scientists listening can use?
Steve Oh [00:17:10]:
So there are a couple of approaches that have been taken. Companies have looked at trying to reformulate alternatives to DMSO using other small molecules like glycerol and additional cryoprotective agents. These are complex formulations that have to be optimized for each cell type.
Then there are companies like X-Therma, which have come up with antifreeze peptide mimics—essentially single-molecule solutions that aim to do the same thing as DMSO but with processing benefits and without the significant toxicity seen with DMSO. So those are the two approaches: either complex formulations or a completely new entity to replace DMSO.
David Brühlmann [00:17:52]:
And looking at X-Therma, I saw that you took inspiration from antifreeze proteins found in Arctic fish. How did this come about? Explain how these specifically protect the cells from freezing damage.
Steve Oh [00:18:06]:
So these antifreeze proteins improve cryopreservation by binding to ice crystals, inhibiting their growth and recrystallization, and reducing damage to cells at sub-zero temperatures. They were derived from cold-adapted organisms and create a thermal hysteresis gap that lowers the freezing point without affecting the melting point, thereby protecting biological samples and enhancing survival rates.
Essentially, how it works is that they cluster around water molecules and prevent the rapid growth of crystals. Because of these much smaller crystals, they don’t damage the cellular structure either when frozen or during thawing. They can return to the liquid state more smoothly than large crystals would, even without traditional cryoprotectants.
David Brühlmann [00:18:55]:
We've just unpacked why DMSO has persisted for six decades despite its well-documented limitations—and why that persistence has real consequences for your cells, your patients, and your manufacturing process.
In part 2, Steve Oh takes us into the solutions—the science behind next-generation cryoprotectants, the data that's turning heads, and what a DMSO-free workflow actually looks like in practice.
If this episode added value, please leave a review on Apple Podcasts or your preferred platform. This enables more scientists like you to discover the show. Thank you for tuning in today—see you next time.
For additional bioprocessing tips, visit us at www.smartbiotechscientist.com. Stay tuned for more inspiring biotech insights in the next episode. Until then, let’s continue to smarten up biotech.
Disclaimer: This transcript was generated with the assistance of artificial intelligence. While efforts have been made to ensure accuracy, it may contain errors, omissions, or misinterpretations. The text has been lightly edited and optimized for readability and flow. Please do not rely on it as a verbatim record.
Book a free consultation to help you get started on any questions you may have about bioprocess development: https://bruehlmann-consulting.com/call
About Steve Oh
Steve Oh is a biotechnology leader with over 35 years of international experience spanning academia and industry. He spent 22 years at A*STAR in Singapore as an Institute Professor at the Bioprocessing Technology Institute, where he pioneered innovations in stem cell bioprocessing, including microcarrier systems, serum-free media, and gene activation technologies.
He holds 43 patents, has published over 150 scientific papers, and has led more than $34 million in research funding. Today, Steve serves as a scientific advisor to multiple global biotech companies, supporting advances in gene therapy, cryopreservation, and cell manufacturing.
Connect with Steve Oh on LinkedIn.
If you’re interested in this topic, check out these episodes, where we explore how Minnesota’s frozen forests inspired a new wave of biotech innovation, transforming how life-saving cells are frozen, stored, and shipped.
Episodes 161 - 162: How to Achieve 85%+ Cell Recovery Without DMSO's Toxic Side Effects with Jeffrey Allen
This is Steve’s second appearance on the podcast. You can also catch his earlier conversation with David, where they explored the challenges and opportunities of cell and gene therapy.
Episodes 11 - 12: From Lab to Patient: Steve Oh’s Guide to Mastering Cell Therapy Process Development.
David Brühlmann is a strategic advisor who helps C-level biotech leaders reduce development and manufacturing costs to make life-saving therapies accessible to more patients worldwide.
He is also a biotech technology innovation coach, technology transfer leader, and host of the Smart Biotech Scientist podcast—the go-to podcast for biotech scientists who want to master biopharma CMC development and biomanufacturing.
Hear It From The Horse’s Mouth
Want to listen to the full interview? Go to Smart Biotech Scientist Podcast.
Want to hear more? Do visit the podcast page and check out other episodes.
Do you wish to simplify your biologics drug development project? Contact Us
For decades, contract development and manufacturing organizations (CDMOs) have grown by building bigger stainless-steel facilities and squeezing ever-tighter margins. But as global overcapacity bites, price wars with Asia intensify, and big pharma pulls production back in-house, the rules of the game are shifting—and standing still might just put you out of business.
This episode, David Brühlmann is joined by Juergen Mairhofer, CEO of enGenes Biotech GmbH, who’s built a career—and a company—around challenging bioprocessing orthodoxy. From developing E. coli strains for single-pot antivenom antibodies to helping major players vertically integrate their supply chains, Juergen Mairhofer’s perspective spans the laboratory, the boardroom, and the demands of a biomanufacturing landscape in flux.
I think the current new Five-Year Plan has been putting bioprocessing at the top next to semiconductors. I think they are going to pull out the same business model as they have been using for the automotive industry, steel industry, and photovoltaics. I think that we will see a replication of that for the bioprocessing industry, and I think the only way out here is to innovate.
And I think also the Chinese industry has understood that they need innovation to become more profitable because currently they are extracting a lot of revenue from Europe and the United States, but they are having a hard time becoming profitable because I think currently they have just been replicating what the industry has been doing over the last 20 years in Europe and the US.
David Brühlmann [00:00:50]:
Welcome back to Part 2 of our conversation with Juergen Mairhofer, who is the CEO of enGenes Biotech. In Part 1, we explored the science behind continuous microbial manufacturing and what makes E. coli such a powerful production platform.
Now we zoom out. In a world of CDMO overcapacity, margin pressure, and shifting geopolitics, does advanced bioprocessing actually become a competitive weapon? And what does it take to build a biotech company from the ground up? Let's find out.
I would come back now to your comments where you said we must innovate. That's a very important point because we live in an industry where we have seen a lot of changes.
And you also said, for instance, synthetic biology — a lot of things have happened since you started. To what extent can the continuous processing you have developed be a competitive advantage, but also a way to lead the way in this evolving industry and finally secure the business and also become an attractive CDMO?
Juergen Mairhofer [00:03:08]:
I think what I can say here is that if you wait for the technology to be completely mature, you will wait for your competitor to pass you. I think this is the point. I see a lot of skepticism when I talk to people. One of the arguments is sometimes: We haven't done that in the past — why should we do that in the future? It's so complicated. And there are all these regulatory aspects that we have to overcome. But at the same time, we also know that the business model in the CDMO space that we are currently seeing cannot go on like it used to.
I think this model is somehow broken, and I think there will be a lot of consolidation in the upcoming months and years. Because in Europe, most of the CDMOs are below €100 million in revenue, so they will have a hard time staying alive at some point. And there is also a lot of pressure from Asia, especially from China. I think the current new Five-Year Plan has been putting bioprocessing at the top next to semiconductors. I think they are going to pull out the same business model they have been using for the automotive industry, steel industry, and photovoltaics.
I think we will see a replication of that model for the bioprocessing industry. And I think the only way out here is to innovate. And I think the Chinese industry has also understood that they need innovation to become more profitable. Because currently they are extracting a lot of revenue from Europe and the United States, but they are having a hard time becoming profitable. I think this is because they have been replicating what the industry has been doing for the last 20 years in Europe and the US.
So they are working with outdated processes, the same outdated processes that US and European CDMOs are still working with. And they have realized that they have to innovate their way out. I think we have to understand that also in Europe and the US the only way forward is innovation, because through innovation we can overcome the cost advantage that countries have where energy and labor are cheaper.
With that understanding, I think the only way forward is to be as innovative as possible, while at the same time trying to overcome the regulatory hurdles as quickly as possible. This will probably not be an easy task, but I think it is a task that is worth working on.
David Brühlmann [00:05:49]:
So what I'm hearing, Juergen, is that the way to stay competitive would be on the technology side, on the bioprocess side, not necessarily on the cost side or the geography, because it's very difficult to compete with that and it's a race to the bottom.
So I'm just trying to wrap my mind around that because we hear about overcapacity in CDMOs, we hear about intense price pressure, and there are a lot of things moving right now. And there are not so many CDMOs that have continuous capacity, for instance. So help us understand how this technological innovation can create a competitive advantage, especially for European or American CDMOs, where the cost of labor is much higher.
Juergen Mairhofer [00:06:36]:
As I said, I think the only solution is to innovate ourselves out of this situation, rather than investing in outdated approaches and trying to extract the last euro or dollar from large-scale stainless steel facilities using outdated technology that doesn't bring any advantage to the customer. Because if you just sell capacity, you are not doing anyone any good. I think this is maybe the major problem we are currently seeing.
By being at the forefront of innovation, you can attract more customers and become more successful. But you have to take some risks. You have to invest in implementing new technologies. You also have to work on a change in mindset, because thinking in terms of a continuous process is not an easy task. I have seen this in my own organization. People have to learn it. But once this learning is accomplished, you unlock many things, because people start to think in a completely different way and become capable of solving problems with less complexity.
That's why I would say: don't be afraid. Push forward into this new landscape and try to adapt before it's too late. Start with a pilot project. Maybe don't start with your most important product, but with a project where you can learn. Find partners like enGenes who master the technology and can enable knowledge transfer, and start now. Because the companies that master continuous processing in the coming years will be the ones that stay competitive. That is what I can say here.
David Brühlmann [00:08:24]:
To what extent, Juergen, will continuous manufacturing become the industry standard in the future?
Juergen Mairhofer [00:08:31]:
I think we will be living in a parallel universe for the next decade, I would assume. I mean, I don't have to tell you what has been built in the past around us. People have been building large-scale stainless steel facilities for CHO, for example, and I think they won't go away. They will stay with us for a long time until they are fully depreciated and the products are probably shifted somewhere else. So they will stay and they will be reutilized.
At the same time, we will see small-footprint continuous manufacturing coming up. So there will be a parallel universe that we have to live and work with. But I think in the long-term future, we will see more and more continuous processes arising on the horizon. Because if we can master the complexity, we unlock so many cost savings and so much increase in productivity that it is worth pursuing that path.
David Brühlmann [00:09:27]:
In this last part of our conversation, Juergen, I would like to talk about your experience and learnings as a company leader. What advice would you give to brilliant scientists who are considering, like yourself, spinning off their technology into a company? What do they need to know about that science alone won't teach them?
Juergen Mairhofer [00:09:49]:
That's a very good question. If you think about it, the honest answer is that your technology doesn't sell itself, no matter how good it is. I think technology excellence is necessary — this is the most important point — but it is not sufficient on its own. The best technology often loses to better-marketed technology. This is something we also had to learn the hard way. There are always people who scream louder, although they don't have superior technology. At the end of the day, they get the financing.
You also have to think from a customer perspective, not just from a scientific one. I think this is a difficult lesson for someone coming from an academic mindset, where you always think: My solution is so brilliant — why don't people care about it? So you really have to try to remove your ego from that perspective.
Another thing I want to mention is that cash is like oxygen. If you run out of cash, it's game over. So this is also something you always have to consider. We have been building the company on revenue, so we always try to onboard new projects. Another point that is relevant: it's not the hard times that are the focus point. You can go through hard times — and you have to — but you have to make the right decisions during the good times. I think this is something people — including me — often forget.
You run through hard times, then you enter good times again, and you think: Okay, let's breathe again. But this is exactly the tipping point where you have to say: Now I have to make the right decisions. And last but not least, I would say the team is everything. I remember writing a quote in my PhD thesis from Joe Strummer, the frontman of The Clash, saying: “Without people, you are nothing.” I think this is one of the most valid quotes for building a company. You can be a brilliant mind as a CEO, but if you don't have a team that is playing the same ball game, you are lost. So focus on the team and treat your people well.
David Brühlmann [00:11:59]:
Yeah, excellent. That's really good advice. Thank you for sharing your experience. Before we wrap up, Juergen, what burning question haven't I asked that you're eager to share with our biotech community?
Juergen Mairhofer [00:12:12]:
I think we could quickly speak about what shifts in the bioprocessing landscape have surprised me most. My answer would be that big pharma is trying to vertically integrate again. When I founded enGenes 12 years ago, the narrative was clear: big pharma outsourced and CDMOs were growing. But I think this is starting to fundamentally reverse. If you think about companies like Pfizer, Eli Lilly and Company, and Novo Nordisk, they are building their own capabilities at massive scale. In-house production is growing again, and the compound annual growth rate is around 10%. Big companies have understood that manufacturing is a strategic asset, not just a cost center. I think this is something they have learned during the last couple of years.
I was just talking to colleagues who came back from a cell and gene therapy conference in the US, and they were saying that big pharma companies have acquired a lot of small innovative companies and are now looking to vertically integrate the supply chain again. When you think about Adeno‑associated virus (AAV) manufacturing, for example, people had been outsourcing the production of raw materials like plasmid DNA. Now they are looking to vertically integrate that again, because these raw materials have been sold at very high prices.
The same is true for Moderna or BioNTech. They also built their own capabilities for producing raw materials for their processes because of the supply-chain issues we saw during COVID‑19 pandemic. I think this is a very big opportunity for enGenes, for example, because we are not directly competing with CDMOs for fermentation capacity. We develop the technology and processes that these companies need, and we can help them vertically integrate and do things on their own again without being dependent on third parties and without incurring very high costs. I think this is a very interesting aspect — that things are going back to where we were 20 years ago.
David Brühlmann [00:14:18]:
We have covered a lot of ground today. What is the most important takeaway from our conversation?
Juergen Mairhofer [00:14:26]:
Don't be afraid, I would say.
David Brühlmann [00:14:29]:
Excellent. Don't be afraid.
Juergen Mairhofer [00:14:31]:
Don't be afraid, and let's innovate our way out. I think all of us in the biotech industry have had a hard time over the last two years or more. The COVID period was tough, and now we see geopolitical shifts, the uncertainties we are confronted with, and all these reshoring initiatives that are ongoing — like the Biosecurity Act, for example. To get back to normal and to stay ahead of the competition, we have to be innovative. Otherwise — as I said before — we will become irrelevant, because the rest of the world is not sleeping. Quite the opposite. Only innovation can help us stay ahead of the competition. That would be my wrap-up of our very nice discussion today.
David Brühlmann [00:15:19]:
Where can a smart biotech scientist who wants to learn more about your E. coli strain and your continuous manufacturing capabilities get in touch with you?
Juergen Mairhofer [00:15:28]:
We have a lot of peer-reviewed publications out there. If you're interested in the technological details, you can dig into those. We currently have an accepted publication in Trends in Biotechnology, together with the Technical University of Denmark, specifically with Andreas Hougaard Laustsen-Kiel’s group. I want to mention that project because it's a very nice one. We have been producing snake antivenom single-domain antibodies in a one-pot bioreactor, significantly reducing the cost using E. coli to produce antivenom therapies for people who are bitten by snakes. Every minute someone somewhere in the world is bitten by a snake, and this approach could help save lives. That’s why we are very proud of this project.
You can also find me at different conferences. For example, I will be in Barcelona at the Bioprocessing Summit, and later in Dublin at the conference of the International Society for Cell & Gene Therapy. If you are close to Vienna, feel free to reach out. I’m always happy to talk with people. I also enjoy helping young entrepreneurs, because I’ve been doing this for 12 years now — growing quite a few gray hairs along the way. I’ve seen many problems, made many mistakes, and I’m happy to share that knowledge if someone needs help.
David Brühlmann [00:16:58]:
There you have it, smart biotech scientists — please take advantage of it. I will also leave the company links in the show notes. And Juergen, thank you very much for sharing your passion and for giving us a wake-up call about innovation. It has been a huge pleasure having this conversation with you today.
Juergen Mairhofer [00:17:18]:
David, thanks a lot for having me. It was a real pleasure discussing with you today. I'm looking forward to feedback from the community about what they think.
David Brühlmann [00:17:28]:
From strain engineering to supply-chain geopolitics to the raw realities of building a biotech company, Juergen Mairhofer brought a perspective you don't hear every day. If this episode made you think differently about where bioprocessing is headed, share it with a colleague and leave a review on Apple Podcasts or wherever you listen. It helps other scientists like you discover the show.
Thank you for tuning in. Until next time — do biotech the smart way. For additional bioprocessing tips, visit www.smartbiotechscientist.com. Stay tuned for more inspiring biotech insights in our next episode. Until then, let's continue to smarten up biotech.
Disclaimer: This transcript was generated with the assistance of artificial intelligence. While efforts have been made to ensure accuracy, it may contain errors, omissions, or misinterpretations. The text has been lightly edited and optimized for readability and flow. Please do not rely on it as a verbatim record.
Book a free consultation to help you get started on any questions you may have about bioprocess development: https://bruehlmann-consulting.com/call
About Juergen Mairhofer
Juergen Mairhofer is a biotech entrepreneur and scientist with deep expertise in genetic and bioprocess engineering. Before co-founding enGenes Biotech, he conducted research at BOKU University and the Austrian Centre of Industrial Biotechnology, where he worked on engineering microbial systems for efficient protein production.
He earned his PhD in Biotechnology in Vienna and has contributed to the field through numerous publications, as well as advanced training in systems biology and microbial genomics. He is particularly focused on driving innovation in microbial manufacturing and next-generation bioprocesses.
Connect with Juergen Mairhofer on LinkedIn.
If you’re interested in exploring more breakthroughs in continuous bioprocessing and the future of biotech manufacturing, check out these past episodes from the Smart Biotech Scientist Podcast:
Episodes 85 - 86: Bioprocess 4.0: Integrated Continuous Biomanufacturing with Massimo Morbidelli
Episodes 153 - 154: The Future of Bioprocessing: Industry 4.0, Digital Twins, and Continuous Manufacturing Strategies with Tiago Matos
Episode 155: From Process Bottlenecks to Seamless Production: How Continuous Bioprocessing Changes Everything
Episode 156: The Hidden Economics of Continuous Processing That Most Biotech Companies Overlook
Episodes 181 - 182: Innovating Continuous Bioprocessing with Vibrating Membrane Filtration with Jarno Robin
Episodes 209 - 210: From Batch to Continuous: Building Innovation Culture in Conservative Biotech Environments with Irina Ramos
David Brühlmann is a strategic advisor who helps C-level biotech leaders reduce development and manufacturing costs to make life-saving therapies accessible to more patients worldwide.
He is also a biotech technology innovation coach, technology transfer leader, and host of the Smart Biotech Scientist podcast—the go-to podcast for biotech scientists who want to master biopharma CMC development and biomanufacturing.
Hear It From The Horse’s Mouth
Want to listen to the full interview? Go to Smart Biotech Scientist Podcast.
Want to hear more? Do visit the podcast page and check out other episodes.
Do you wish to simplify your biologics drug development project? Contact Us
What if continuous microbial manufacturing wasn’t a pipe dream, but a reality quietly reshaping the foundations of bioprocessing?
Stuck in the cycle of fed-batch fermentation, the industry has long treated genetic drift and instability as unavoidable limitations—especially with E. coli. But what if the root of these headaches lies not in the hardware or facility layout, but deep within the biology itself?
Today's guest on Smart Biotech Scientist Podcast with David Brühlmann is Juergen Mairhofer, CEO of enGenes Biotech GmbH. Juergen is a scientist with a rare dual fluency in molecular biology and bioprocess engineering.
The solution to the problem is the genetic stability. Because with this high replication rate of microbial cells, you always have this genetic drift. And this is already pronounced in a simple fed-batch process. But when you start to do that in a continuous manner, the process has to be terminated within a few days. Because if you use a classic cell line, the cells will mutate so quickly and there will be no productivity within 4 to 5 days.
David Brühlmann [00:00:31]:
What if the biggest bottleneck in bioprocessing isn't your downstream equipment or your facility design, but the production host itself? Today I'm joined by Juergen Mairhofer, who is the CEO of enGenes Biotech, who has spent over a decade engineering smarter microbial platforms and pioneering continuous manufacturing using microbial cells for recombinant proteins and plasmid DNA. In this conversation, we dig into what it actually takes to move from batch thinking to continuous reality. Let's dive in.
Welcome, Juergen, to the Smart Biotech Scientist. It's good to have you on today.
Juergen Mairhofer [00:02:25]:
Great, David, to be with you today, and I'm really looking forward to this very nice conversation.
David Brühlmann [00:02:30]:
Juergen, share something that you believe about bioprocess development that most people disagree with.
Juergen Mairhofer [00:02:37]:
That most people disagree with. I don't want to be provocative here, but I think that the commodity CDMO model rewards utilization over innovation, and that's why it's becoming unsustainable. So what we know is that CDMOs optimize for utilization of their existing steel tanks and not really for the productivity of the process. I think the problem that we are seeing in the industry and the traditional business model they are driving rewards risk minimization and capital utilization on their end, and they are not really willing to innovate.
When you make money by selling fermentation time, you have zero incentive to make processes faster and more efficient. I think this is the core problem or the root cause of the problem. And when you look into documents like a recent report from Roland Berger, the data in there shows that CDMOs with the right business models, really focused on innovation, can avoid significant price pressure. This is exactly the point.
So the commodity model is under severe pressure, while innovation-focused players thrive. And we at enGenes Biotech deliberately didn't build enGenes as a traditional CDMO.
So our model is based on real process development using proprietary technologies and then out-licensing these technologies. So enGenes makes money when the process gets better, not when it gets longer.
So this is the basic principle, and this aligns our interests with those of our customers. So we are the innovation partner that CDMOs and pharma companies are in need of in these difficult times.
David Brühlmann [00:04:24]:
Before we dive a bit further into your CDMO model and what exactly you're doing in process development, draw us into your story, Juergen. What sparked your interest in biotechnology and what were some pivotal moments leading to your current CEO role?
Juergen Mairhofer [00:04:42]:
So what are the pivotal moments? I think the pivotal moment was when I started my master's thesis here at the University of Natural Resources and Life Sciences, Vienna (BOKU), where I did host cell engineering, so classical molecular biology, and where for the first time in my life I could be creative in a way without other people judging my creativity.
Because if you do painting or something like that, everyone can say, okay, this doesn't look like a dog. But if you pipette small volumes in an Eppendorf tube and you have to wait for four weeks until you get a dataset out, in between nobody can judge whether the creative process is good, bad, or whatever.
So with my supervisor at that time, I learned that creativity is something really amazing. And being raised in a home where everything was macro, because my father is a car mechanic, things were judged immediately because you can just do things right or you can do things wrong. But with molecular biology, you have to try and you have to learn whether things work out.
And this is where the creative process started. Being at that time, I think 24, I think it was the first time in my life I learned what creativity can really bring to the table.
And there was no judgment in academia. So we were able to try things out and see if things worked out. And we were following a lot of weird ideas at that time point because this was the time when synthetic biology was born more or less. So starting around 2002, I think, with the first publications. And I ended up in a very dynamic field and I really appreciated that. So being able to be creative, I think this was the spark.
And then having the opportunity to do a PhD together with a big pharma company - my PhD project was funded by Boehringer Ingelheim at that time -, and getting also an idea of how big industry works.
Then being able to do two more additional postdoc positions, for example with the Austrian Centre of Industrial Biotechnology (ACIB), I also got more and more insights into how the industry works. And at the end of the day, I realized that the big pharma industry is not the place where I want to grow old.
So I come from a sort of DIY perspective. I grew up in the countryside in the 1990s, where nothing was going on, so it was very boring. When we wanted to have fun, we had to build our stuff on our own.
And I think with that mentality, I was able to develop the mindset to start thinking about founding my own company. And I think that's the point where everything started. So being passionate about being creative, building stuff on my own, and then also having the guts and coming from a hard-work mentality to really dig into a topic and make it work. So I think this is what got me into founding my own company.
David Brühlmann [00:07:39]:
Yeah, I love the way you're looking at pharma, looking at creativity where a lot of people see regulatory constraints. It's a pretty good way to look at it. And then on top of that, your entrepreneurial mindset and also hard work. And I think that's definitely a sweet spot. So tell us a bit more about what you're doing now with your company, how you are translating scientific innovation into scalable bioprocesses and more?
Juergen Mairhofer [00:08:09]:
As I started to explain, I was always working at the intersection of molecular biology and bioprocess engineering. So this was quite new in the early 2000s. It was the field of synthetic biology coming up, and at that time people were used to working in silos.
So there were people doing molecular biology, and then there were the bioprocessing people, and within the bioprocessing community there were the upstream people and the downstream people, and none of them were really able to communicate with each other because they had different mindsets and they spoke different technical languages.
And the funny thing was that within my PhD project, it was located directly at that intersection. Meaning we had to engineer a strain, to build a new Escherichia coli (E. coli) strain with a lot of genetic features to be able to perform certain tasks.
And I brought that strain to another working group at the university doing upstream processing. And I think I was one of the first people who was a molecular biologist and then also running fermenters at that time. So that was quite unusual. I had to really work hard so that these people would take me seriously.
But at some point they started to understand that this knowledge has a lot of value because it's like an iterative cycle. This is what I implemented here at the university, saying: Okay, we have to engineer the strain to meet the requirements of a bioprocess, and then we have to look at how the strain behaves in a real bioreactor, not in a shaker flask.
And then once we have learned that, we have to go back and improve the strain, and we have to run this cycle iteratively several times until we have an output that meets our requirements. So this is how I learned to work with the tools I had at that time, and this was fundamental, I think, to founding enGenes Biotech. Because all the work we are doing is based on a proprietary E. coli host strain that I invented together with colleagues.
So what we are capable of doing is that we can decouple protein production from cell growth. At a dedicated time point in the bioprocess, we can stop cell division and at the same time switch on the protein production process, which is using an orthogonal transcription system.
So in that case, T7 RNA polymerase, which then massively overtranscribes the gene of interest. And by having this non-dividing cell population, we can fill the cells with recombinant protein, or we can even secrete the protein to the extracellular space.
At the same time, this also genetically stabilizes the manufacturing system. Because one of the big drawbacks of using bacteria is that they have a very rapid growth rate. So they have a very high turnover. Every 20 minutes you generate progeny, you have an exponential growth function. And due to that fast growth, the genetics of the cells drift, because you always generate variability within your population.
At some point you end up with a cell that no longer has the plasmid where your gene of interest is located, or it has a mutation in some intracellular function. This cell can then overproliferate in your bioreactor and stall your production type. By stopping cell division, you can derail that process. So you're derailing adaptive evolution, and thereby we were able to come up with a very stable and robust manufacturing system that we finally commercialized within enGenes Biotech. And this is where the story started about 12 years ago.
David Brühlmann [00:11:33]:
What kind of products are particularly well suited to produce in your specific strain?
Juergen Mairhofer [00:11:39]:
Everything that you can produce using E. coli, so that is non-glycosylated, we are happy to take over this challenge because we believe that the non-growth-associated production is most of the time beneficial over the growth-associated production.
Because growth-associated production has these drawbacks that I already addressed, namely that the cells try to escape from the burden of producing whatever — let's say recombinant protein, plasmid DNA, or a small metabolite — it doesn't really matter. They want to escape because their objective function is to generate progeny as fast as possible, and they have absolutely no interest in serving the bioprocess engineer.
On the other hand, you have to come up with a smart solution to get the cells to the point where they have to do what you want them to do and to reduce the degrees of freedom that they have. And by playing this trick that we are implementing on the molecular biology level, we block the RNA polymerase of E. coli, so the cell can no longer produce its own messenger RNAs (mRNAs). And therefore it cannot ramp up a stress response, because the stress response is always meant to escape the metabolic burden you exert on the cell by forcing it to overproduce your biomolecule of interest.
David Brühlmann [00:12:57]:
And if I may put it simply, basically your cell line gets you a much higher titer, correct? Because you have more energy available for your protein of interest.
Juergen Mairhofer [00:13:08]:
Absolutely. So all the metabolic resources are channeled into production of the protein of interest, or replication of a plasmid, or production of a bioconjugate. And this allows us to come up with very high-titer processes, and at the same time processes that are very scalable, because we don't have this process variability that can happen through plasmid loss or accumulating mutations.
So also in the scale-up process, the processes we develop are much more robust and stable. And I think this is the big advantage of the technology that we are using.
David Brühlmann [00:13:45]:
And what is now the ratio between traditional fed-batch processes and continuous processes in your programs? Because I know you're big on continuous, but what is the current ratio?
Juergen Mairhofer [00:13:57]:
I mean, the current ratio, to be honest, is that we have been developing microbial continuous processes, and we are the first movers in that field. So I don't know of any other company that has successfully accomplished running an E. coli process fully continuous for the amount of time — days — that we have achieved. So we are currently talking about 40 days. So I think we are the first mover here.
We are currently trying to scale up our process on our own. Right now it's running at the 1-liter scale, already very productive with a small footprint. But at the end of the day, we are looking to scale that up to the 100-liter scale producing bioreagents.
So this is what we are currently looking into, and we are looking for partners who are willing to adapt this process scheme for biopharmaceuticals, for example. So insulin would be an amazing case, because this is something that needs to be produced at massive scale. At the same time, the costs have to be low.
What we are struggling with at the end of the day is what you mentioned earlier — the industry is very risk-averse and conservative. For mammalian cell culture, continuous processing is taking off at the moment. So we see that there is a lot of interest in that. Very few companies are able to master it, but some of them are. But for microbial bioprocessing, I think we are just at the beginning. So this is something we have to push forward now. We see that it is getting traction, but it needs someone who is willing to adopt it and to further develop it together with us.
David Brühlmann [00:15:33]:
What is the reason that E. coli is lagging behind? Because as you said, several companies are mastering continuous processing with CHO, but what is more complex — either on the technical side, or perhaps there are economic factors in E. coli processes that explain that?
Juergen Mairhofer [00:15:48]:
The solution to the problem is, as I have explained before, genetic stability. Because with this high replication rate of microbial cells, you always have this genetic drift. And this is already pronounced in a simple fed-batch process. But when you start to do that in a continuous manner, the process has to be terminated within a few days.
Because if you use a classic cell line, the cells will mutate so quickly that there will be no productivity within 4 to 5 days. That's what we've been seeing by using the classical E. coli BL21 strain, for example, in head-to-head comparison with our technology.
So this effect is really pronounced in continuous mode, and I think the tools haven't been available to tackle that. But now with our technology, we have a genetically stabilized host cell, and we have a proprietary approach to how we do things. Because we do not run the continuous process just in one vessel — a chemostat. We run it in two connected chemostats.
This adds a bit of complexity, but at the same time it solves the problem of genetic stability. In the first vessel we grow our cells, so that is where biomass production is going on. Then we pump our cells into a second vessel where we decouple protein production from cell growth. We stop cell division in the second vessel, thereby genetically stabilizing the system, and then the production goes on in the second vessel. And we are in a fully steady-state condition. So everything that goes in on one side is equal to what goes out on the other side.
And by applying that trick, we end up with a productive process for up to one month. So this is the solution to a complex problem, and I think people have been struggling a lot to solve that. But the solution is now out there. Whenever somebody has an interest in doing that, we can start straight away.
David Brühlmann [00:17:39]:
With now 30 days in continuous mode with E. coli, how do you run the DSP (downstream processing)? Is that continuous, or are there several batches followed by each other?
Juergen Mairhofer [00:17:50]:
The project we have been working on with a larger consortium here in India is a fully end-to-end continuous process. So the upstream is continuous, then the primary recovery. In that case, we have our product — a Protein A ligand — in the supernatant. So we have to separate the biomass from the supernatant. This is done by continuous dynamic filtration.
Then we end up with a clear permeate where our product is located. And this is then captured by a multi-column chromatography approach where we have four columns that are run in series. So every time two columns are loaded, one is eluted, and the fourth column is regenerated. And by assembling all these continuous unit operations, we came up with a very intensified process.
All the learnings we have from changing our mindset in that project to a fully continuous approach can be injected directly into the classical things we are doing in fed-batch mode, because the learnings in process intensification can also be applied to the classical fed-batch principle. So it's about how to do things in the most efficient way.
Because what is very important in continuous production is that you have a robust setup, since you cannot tolerate failure. Everything has to be very robust and very effective, otherwise you cannot master such an endeavor.
David Brühlmann [00:19:11]:
What are the main advantages of a continuous process with E. coli? Many of the listeners are familiar with continuous processes with CHO cells. Are you seeing similar advantages or are they very different?
Juergen Mairhofer [00:19:25]:
I think it's quite similar because what are the main advantages? You want to produce more with less, meaning less facility footprint, less capital expenditure (CAPEX). So you want to invest in a small facility, not build a 10-cubic-meter stainless steel facility. You probably want to build a single-use facility that you can fit into a ballroom concept or something like that.
And you want to have less operational expenditure (OPEX). Meaning if it's fully automated and digitalized, you can also save costs on the level of personnel. I mean, the process that we had up and running required only one person available who was looking at the process from a meta perspective, also being able to send out SMS alerts if things were going wrong or if there was a process deviation.
You can really start to think on a different level. Not having 120 people running around like crazy, but trying to have a process that runs with a small footprint and a low headcount. I think this is what we have to do to innovate and to stay competitive in the race that we are seeing at the moment on a global level. If we are not willing to innovate, we will become irrelevant. I think this is absolutely the problem we are facing.
David Brühlmann [00:20:45]:
Yeah, this is a good point, and I would like to touch upon innovation a bit later. I just want to ask a question about what can go wrong with an E. coli continuous process, because even with CHO, it's no easy endeavor in certain cases to run a process for 30, 45, or even longer days. What are the main reasons or issues you have observed that can go wrong?
Juergen Mairhofer [00:21:10]:
The main issues that can go wrong: genetic stability first and foremost. That is, I think, the major obstacle, as already elaborated.
This is something we had to learn and improve stepwise. Genetic stability on different levels:
Then other issues like sterility can also be a concern. We haven't seen a lot of contamination because we are very good at working aseptically, but if you want to have something running for more than two weeks, it can become a problem at some point.
Especially when you think about single-use equipment, where the systems are most of the time validated only for about 10 days or something like that. So this is still an open question — whether you can reliably run single-use equipment for extended periods.
Another topic is leachables. Is there a leaching issue, especially in microbial processes where you might use ammonia? Is this more pronounced compared to CHO processes? That is a question to be addressed in the future. Then there is also the complexity of connecting multiple unit operations continuously. This can create challenges because if something changes in the upstream, it can have a major impact on the downstream.
We solved that by building models around our process, implementing hybrid or mechanistic models. One of the nice things I can mention here is that we are able to determine the product yield every 15 minutes online. We have an HPLC standing next to our continuous process that measures the titer and then injects that data point into a mechanistic model. This mechanistic model counts, for example, the cycles on the multi-column chromatography, so we know how the columns age.
Based on this knowledge, we can then call the optimal purification method determined by the mechanistic model to purify the protein at the current concentration in the supernatant. These are the feedback loops that you can implement to make your life easier.
And then, as I mentioned earlier, through automation you can solve many problems on the fly. For example, if readings show that the back pressure is increasing on the filtration device, the system can send a warning message to someone near the system to check it and counteract the issue early. That way you avoid something like a burst connection due to rising back pressure.
David Brühlmann [00:24:13]:
This wraps up part one of our conversation. From growth-decoupled production to the real engineering challenges behind continuous microbial manufacturing, Juergen is giving us a masterclass in rethinking how we scale bioprocesses. And we're just getting started.
In Part 2, we shift gears into the business side — CDMOs, geopolitics, and the founder's journey. If you're enjoying this episode, leave a review on Apple Podcasts or your favorite platform. It truly helps other scientist like you discover the show.
For additional bioprocessing tips, visit us at www.smartbiotechscientist.com. Stay tuned for more inspiring biotech insights in our next episode. Until then, let's continue to smarten up biotech.
Disclaimer: This transcript was generated with the assistance of artificial intelligence. While efforts have been made to ensure accuracy, it may contain errors, omissions, or misinterpretations. The text has been lightly edited and optimized for readability and flow. Please do not rely on it as a verbatim record.
Book a free consultation to help you get started on any questions you may have about bioprocess development: https://bruehlmann-consulting.com/call
About Juergen Mairhofer
Juergen Mairhofer is co-founder of enGenes Biotech and a biotechnology expert specializing in microbial cell design and bioprocess engineering. He previously worked as a Research Associate at BOKU University in Vienna and as a PostDoc at ACIB, focusing on recombinant protein production and strain engineering.
Juergen holds a PhD in Biotechnology and has authored multiple scientific publications and book chapters. His work centers on translating advanced genetic technologies into scalable industrial solutions.
Connect with Juergen Mairhofer on LinkedIn.
If you’re interested in exploring more breakthroughs in continuous bioprocessing and the future of biotech manufacturing, check out these past episodes from the Smart Biotech Scientist Podcast:
Episodes 85 - 86: Bioprocess 4.0: Integrated Continuous Biomanufacturing with Massimo Morbidelli
Episodes 153 - 154: The Future of Bioprocessing: Industry 4.0, Digital Twins, and Continuous Manufacturing Strategies with Tiago Matos
Episode 155: From Process Bottlenecks to Seamless Production: How Continuous Bioprocessing Changes Everything
Episode 156: The Hidden Economics of Continuous Processing That Most Biotech Companies Overlook
Episodes 181 - 182: Innovating Continuous Bioprocessing with Vibrating Membrane Filtration with Jarno Robin
Episodes 209 - 210: From Batch to Continuous: Building Innovation Culture in Conservative Biotech Environments with Irina Ramos
David Brühlmann is a strategic advisor who helps C-level biotech leaders reduce development and manufacturing costs to make life-saving therapies accessible to more patients worldwide.
He is also a biotech technology innovation coach, technology transfer leader, and host of the Smart Biotech Scientist podcast—the go-to podcast for biotech scientists who want to master biopharma CMC development and biomanufacturing.
Hear It From The Horse’s Mouth
Want to listen to the full interview? Go to Smart Biotech Scientist Podcast.
Want to hear more? Do visit the podcast page and check out other episodes.
Do you wish to simplify your biologics drug development project? Contact Us
For many biotech innovators, high throughput screening platforms promise faster discoveries and streamlined workflows. Yet beneath the glossy veneer, the reality often feels more complicated—requiring hands-on expertise, careful assay design, and a sharp understanding of microbial physiology just to avoid costly missteps.
Smart Biotech Scientist Podcast host David Brühlmann is joined by Sebastian Blum, a microbiologist with more than two decades in the life sciences and now Market Development Manager at Beckman Coulter Life Sciences.
Some believe that high-throughput screening is a kind of black box, where you throw a sample in and it spits out the perfect hits. And automation is often misunderstood as synonymous with simplicity. The reality is, high-throughput screening is highly complex. It requires very careful assay development and validation, a deep understanding of the biology, precise robot programming, and sophisticated data analysis. The system must be calibrated, maintained, and constantly monitored. Misunderstanding this can lead to suboptimal decisions, especially when the team believes it’s “just pushing a button” and underestimates the need for highly specialized personnel.
David Brühlmann [00:00:38]:
Welcome back to Part Two with Sebastian Blum from Beckman Coulter Life Sciences. We’re continuing our conversation on mastering early-stage bioprocess development. Here is Part One of our conversation. We’re talking about practical guidance on choosing between shake flasks, benchtop bioreactors, and high-throughput platforms, and understanding when each approach makes sense for your specific application. We’re also covering the common pitfalls that trip up even experienced teams and how to avoid them. Thanks to Beckman Coulter Life Sciences for making this episode possible. If you want to make smarter screening decisions and save months of troubleshooting, this episode is for you. Let’s dive back in.
What would you tell a startup founder who says, “Well, I’m interested in the BioLector XT Microbioreactor because the system looks great. We can test a lot of things and move quickly,” as many startups want to do. But from your answer, Sebastian, it seems you also need some technical background to use the system correctly. Would you advise for, against, or under what conditions would you say no? This makes sense. You will get the most out of using a BioLector XT Microbioreactor.
Sebastian Blum [00:03:04]:
Normally, when a customer comes to us, or we approach a customer, we talk intensively about their applications. Just as an example, we had one academic customer who wanted to do strictly anaerobic cultivations with a very low OD—starting at 0.x and wanting to induce at 0.x. When we recognized this, we saw that it didn’t match the BioLector XT Microbioreactor specifications, which work from OD 1 up to, let’s say, the sky is the limit because of the scattered light measurement.
We try to understand how important this is for the customer. When he told us it was essential for his process, we said, “Okay, then the BioLector XT Microbioreactor is the choice for him.” So this can happen, but it’s application-dependent.
LUA scripting is not often used in academia. Interestingly, it’s more common in industry, where you might want to combine different feeding modes in one run to mimic larger fermenters, which may switch from exponential to linear or constant feeds. This is possible with LUA scripting, but it does not happen too often. Of course, if customers ask for it, the solution is there. If they cannot handle LUA scripting themselves, we can do it for them. This is normally not a showstopper.
David Brühlmann [00:04:22]:
So what are the scenarios in which it makes the most sense to use the BioLector XT Microbioreactor?
Sebastian Blum [00:04:28]:
I would say anything related to process development, like finding the right parameter combinations—media, pH, induction, induction profiling—and where there’s a need for flexibility across different microorganisms. For example, CDMOs need to be very flexible because they serve multiple clients with different microorganisms and applications.
The BioLector XT Microbioreactor is a very good fit, especially because we can upgrade modules depending on the application. For instance, a customer can start with a simple batch system, then upgrade to a microfluidic system to allow feeding and pH control for up to 32 wells. If the customer requires an anaerobic application, the system can be upgraded with an anaerobic module to perform feeding and pH control under strictly anaerobic conditions.
If offline analytics are needed, the whole system can be integrated with a Beckman Coulter Life Sciences Biomek i5 or i7 workstation to leverage full automation advantages.
So, if a customer needs flexibility, is screening a lot of parameters, and is trying to find the best conditions, that’s where the BioLector XT Microbioreactor excels.
David Brühlmann [00:05:54]:
So that means it’s particularly suited for early-stage screening, correct?
Sebastian Blum [00:05:58]:
Yes, exactly. That accounts for 99% of our systems, placed in upstream development for early R&D screening.
David Brühlmann [00:06:06]:
Speaking of automation and Biomek, where do you see companies typically place the BioLector XT Microbioreactor in their workflow?
Sebastian Blum [00:06:13]:
As I mentioned before, there’s upstream development, downstream development, and finished production. Typically, we see the system used only in upstream development. That’s where you do strain development, identify the best media, and set up initial culture conditions for optimal growth and productivity.
David Brühlmann [00:06:35]:
What are the most common misconceptions you see in scientists who want to acquire a BioLector XT Microbioreactor or already have one? From what we’ve discussed, it’s a powerful tool. You can do a lot of things, but sometimes it's also about managing expectations and helping people use the technology best. What misconceptions do scientists generally have about high-throughput screening systems?
Sebastian Blum [00:07:02]:
Some believe that high-throughput screening is a black box—you put a sample in, and it spits out perfect hits. Automation is often misunderstood as synonymous with simplicity. The reality is, high-throughput screening is highly complex. It requires careful assay development and validation, a deep understanding of the biology, precise robot programming, and sophisticated data analysis.
The system must be calibrated, maintained, and constantly monitored. Misunderstanding this can lead to suboptimal decisions. When teams think it’s “just pushing a button,” they underestimate the need for highly specialized personnel.
As a result, they might underinvest in assay development or bioinformatics expertise, leading to poorly designed assays, unreliable data, high error rates (false positives or negatives), and ultimately a loss of valuable time and resources because results cannot be interpreted or reproduced.
So the “black box” idea is a misconception. It’s not that simple—you can’t just put something in and automatically get the perfect hit.
David Brühlmann [00:08:02]:
This is very well said. I’ve done a lot of deep-well plate experiments in my career, and understanding the process side and analytics is just as important. Thank you for highlighting this, Sebastian.
Looking ahead, with more technology on our end—robotics, automation, and now AI—I’m curious about your perspective. How do you see early-stage bioprocess development evolving in the future?
Sebastian Blum [00:08:34]:
What I see is more automation and miniaturization. There's a clear tendency in this direction. So we are going to see even higher throughput, more sophisticated microbioreactor systems, and a lot more integration of robots for end-to-end automation workflows—from media preparation all the way to sample analyzers. AI is the buzzword, and you see it at every conference at the moment as well.
The huge amounts of data that high-throughput screening generates will increasingly be used with artificial intelligence (AI) and machine learning (ML) for predictive modeling—really fast identification of optimal conditions and a much deeper understanding of the mechanisms at play. It’s going to move beyond just finding what works to understanding why it works. So I see a lot of potential for AI, and that trend is clearly moving in this direction.
What I see as well, especially in larger industries, is more use of digital twins and process simulations. We can expect the development of more robust in silico models, basically digital twins of bioprocesses. That will let scientists simulate thousands of scenarios virtually before they even perform a physical experiment, which will speed up optimization even more. I think that’s still somewhat the future, but I see that customers are already discussing this idea and goal.
I still think some skills will always remain critical—the core bioprocess engineering principles. You still need a fundamental understanding of microbial physiology, cell biology, fluid dynamics, mass transfer, and reaction kinetics. The tools might change, but those underlying biological and engineering principles are constant, in my opinion.
Of course, you also need critical thinking and problem-solving skills—the ability to evaluate data critically, identify the root causes of problems, and design robust experiments. These will always be at the heart of successful development.
David Brühlmann [00:10:24]:
Before we wrap up, Sebastian, what burning question haven’t I asked that you’re eager to share with our biotech community?
Sebastian Blum [00:10:33]:
Honestly, David, your questions have been very good. I’ve also watched your podcast in the past and was impressed by the spectrum you cover. In my opinion, everything relevant was discussed here. I really appreciate your questions and the podcast—thank you for having me.
David Brühlmann [00:10:52]:
Great. Thank you very much for the feedback—it’s always wonderful to hear directly from our guests.
David Brühlmann [00:10:58]:
By the way, if you have feedback about the Smart Biotech Scientist Podcast, please leave a review. This means the world to me. Sebastian, what is the most important takeaway from our conversation?
Sebastian Blum [00:11:13]:
In my opinion, it’s to carefully consider where to implement high-throughput screening tools in your process and evaluate the need and advantages for your specific application. I hope I’ve highlighted the possibilities that customers have by using the BioLector XT Microbioreactor. Above all, I encourage people to stay curious, stay critical, and choose the right tool for the right job.
David Brühlmann [00:11:45]:
Fantastic, Sebastian. Thank you for helping us understand the key success principles for early-stage screening and sharing your insights. Where can people learn more about the BioLector XT Microbioreactor and get in touch with you?
Sebastian Blum [00:12:00]:
The Beckman Coulter Life Sciences website has a lot of information about the BioLector XT Microbioreactor, including publication lists, application notes, and a gallery showing how the system works. There’s also a small training section. If someone is interested in Europe, I’m available as the Market Development Manager to guide them as needed.
David Brühlmann [00:12:29]:
Excellent. I’ll include that info in the show notes. Once again, thank you very much, Sebastian, for being on the show today.
Sebastian Blum [00:12:37]:
David, it was a pleasure. Thank you.
David Brühlmann [00:12:40]:
Thanks for joining us today for this deep dive into bioprocess screening strategy. Remember the right early stage decisions, save months of troubleshooting downstream. If today's conversation gave you actionable insights for your own development work, please leave us a review on Apple Podcasts or whatever platform you're listening on. It truly makes a difference. Thank you so much for your feedback. I love hearing from you. And until next time, keep doing biotech the smart way.
All right, smart scientists, that’s all for today on the Smart Biotech Scientist Podcast. Thank you for tuning in and joining us on your journey to bioprocess mastery. For additional tips, visit www.bruehlmann-consulting.com. Stay tuned for more inspiring biotech insights in the next episode. Until then, let’s continue to smarten up biotech.
Disclaimer: This transcript was generated with the assistance of artificial intelligence. While efforts have been made to ensure accuracy, it may contain errors, omissions, or misinterpretations. The text has been lightly edited and optimized for readability and flow. Please do not rely on it as a verbatim record.
Book a free consultation to help you get started on any questions you may have about bioprocess development: https://bruehlmann-consulting.com/call
About Sebastian Blum
Sebastian Blum has spent over two decades in the life sciences industry, with a background in biology and microbiology. He is currently Market Development Manager at Beckman Coulter Life Sciences, focusing on high-throughput screening technologies for bioprocess development.
In 2010, he discovered an innovative micro-fermentation system that sparked his interest in transforming early bioprocess workflows. Motivated by strong researcher feedback, he joined m2p-labs in 2011 to help advance the technology. Following the acquisition of m2p-labs by Beckman Coulter Life Sciences, Sebastian embraced the opportunity to continue the journey within a global organization.
Connect with Sebastian Blum on LinkedIn.
David Brühlmann is a strategic advisor who helps C-level biotech leaders reduce development and manufacturing costs to make life-saving therapies accessible to more patients worldwide.
He is also a biotech technology innovation coach, technology transfer leader, and host of the Smart Biotech Scientist podcast—the go-to podcast for biotech scientists who want to master biopharma CMC development and biomanufacturing.
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