What happens when the charging elephant of biotech—antibody-drug conjugates (ADCs)—meets the organizational complexity of a 300-strong analytical powerhouse? The answer isn’t just in the science; it’s in how you marshal people, tech, and trust to outpace the clock and deliver therapies that matter.
This episode features Amanda Hoertz, VP of Analytical Development & Testing at KBI Biopharma. Amanda’s spent her career navigating the thicket of biologics—from biosimilars to the most challenging ADCs—while shepherding one of the largest analytical teams in the industry. Her perspective isn’t just tactical: it’s rooted in tenacity, team stewardship, and a practical playbook for bringing next-generation modalities to market. Check the first part of our conversation.
We definitely look at each molecule individually, but with the experience behind us. So as I mentioned, our tenure before - that's a huge advantage. We remember the molecules that are similar. There are a number of biosimilars where it's not the first time they've come to KBI. So we kind of have an idea of where to go down that path, and that really helps us accelerate for later clients.
The same thing with ADCs: if we know what molecule or method is going to be the trouble method—so I've already said that's the charge heterogeneity—we know to start with that method first in our method development.
David Brühlmann [00:00:36]:
Welcome back to Part Two of our conversation with Amanda Hoertz from KBI Biopharma. I'm your host, David Brühlmann, and in part one we explored Amanda's journey and the fundamentals of ADC development.
Now we are diving into the nitty-gritty: the analytical puzzles, the formulation challenges, and the scaling strategies that make ADCs so complex. Amanda will share KBI’s innovative approaches, leadership insights from managing 300 scientists, and the future trends shaping biologics development.
Let's shift our conversation towards the more, I'd say, project management or organizational aspects. What are some key best practices you follow at KBI to accelerate the path of ADC development?
Amanda Hoertz [00:02:46]:
So the approach is the same whether it's ADC or non-ADC. What we've found at KBI works best is we have a program manager, and that stays the same for the client. But then we also have dedicated teams in each space.
Once you have a dedicated director and group leader—for example, in the analytical space—that will be the same person you work with for the life of the project. It helps because we learn what this customer wants versus that customer. Right?
This customer may want all the raw data exported and sent to them on a secure shared drive so they can make overlays. Another client may not need that. One client may want everything in a PowerPoint presentation, one may not. One may have a critical filing deadline, one may not.
So by having a consistent point of contact—and that contact will stay the same if you have another molecule at KBI—you don’t have to relearn that relationship. Everything is consistent. You know how to get what you need, and you also know when they need something for, let's say, an IND update. You understand who to talk to, and you know what they need. It's a good relationship. If the client invests in it and KBI invests in it, it makes everything a lot faster.
What we've seen at some CDMOs that we outsource services to—for example, sterility testing and CCIT (Container Closure Integrity Testing)—it’s very confusing as to who to talk to. So when we have investigations at those other partner sites, and we are responsible for the relationship, I sometimes struggle to get answers out of a director or somebody at a different company. Not going to name names because I don't want to badger anybody in particular, but it's confusing.
And I can only imagine as a client, when you have a critical filing for your IND and you need this file now—if you don’t know who to contact or can’t get a clear tree of responsibility—how frustrating that would be. So we try to make sure that it’s seamless.
I'm not pretending that KBI is perfect. There are definitely times when a client needs something and the timeline is insane. We try to meet it and do everything we can.
That’s one of the strengths of the analytical portion of KBI. So, a typical CDMO has a QC team of about 20 to 30 people that execute testing—usually release and some limited stability. KBI, at the Hamlin site alone, has 200 analysts, and in the network it’s 400—300 of which are under my supervision.
It means that if you need something as a client, I can throw basically a flood of people and a flood of instruments on something to make sure you get what you need. It's an army. We can absolutely destroy any task by rearranging priorities.
And that’s one of the benefits of having the mammalian network for analytical testing under me, and the process development mammalian network under Leslie Wolfe at KBI, is that we can adjust priorities in real time. There’s no in-depth conversation or negotiation.
And even with our microbial partners, we leverage each other’s teams to make sure that we get what the client needs. We have excellent relationships across our entire network.
David Brühlmann [00:05:40]:
Having that many people is impressive, and it can definitely be an advantage if you manage your network well—or your people well.
So my question, Amanda: how do you ensure consistency and knowledge transfer among this huge army? And what is your framework for building analytical methods that are robust and scalable?
Amanda Hoertz [00:06:01]:
I can’t take credit for this because I’m benefiting from my parentage at KBI—they’ve set this up in a very scalable way.
So, at the Hamlin site specifically, there are about 200 people. We have eight directors, and then below the directors are group leaders. Below the group leaders are project leaders. So it’s a very structured tree, and that structure drives knowledge transfer as well.
Basically, we’ve all been “raised” in this environment. The average tenure at the North Carolina Analytical and Formulation Sciences (AFS) group is almost six years. And the average tenure for managers is close to 10 years. That is atypical for the industry, and it’s really the key to our success.
We very much advocate for our people. That’s my job—making sure I’m doing everything I can for the analysts all the way up to the managers. And those managers do the same. That inspires a lot of loyalty and consistency.
If we’re not constantly turning over analysts, we can benefit from their knowledge base and also have the bandwidth to do improvement projects. Analysts are, of course, the most common turnover point, but even there the average tenure is almost four years—compared to the industry average of around two years. That’s a big difference, and we benefit from it.
I think once you have a good culture, it’s actually easier to maintain it. But when you allow that to degrade, that’s when you start to face bigger problems. So I can’t take credit for creating it—I’m just trying to maintain what was entrusted to me when I started leading the department. That’s how so many people can work together effectively.
We also all have the same mentality: we know we need to deliver for the customer. There’s no confusion about priorities, and we have a very clear decision tree.
If I talk to one of my directors who’s working on a project and I say, “This other project has reached a critical status and we need to rearrange priorities,” first of all, we have the depth to move things around. Second, everyone understands how that priority was determined—and then it’s done.
And it works the same way for me. If my boss, Sigma Mostafa, our Chief Scientific Officer, tells me, “I need you to make sure this client or this activity is completed,” we just do it. Not in a military way, but in the sense that it’s clear: the decision has been made, now it’s time to execute. That clarity really helps.
David Brühlmann [00:08:08]:
That’s fantastic. I think clarity is key, and it’s great that you can leverage this huge network. So I’m curious, Amanda—you mentioned the culture is great and you put a lot of work into it. But on the technical side, how has digital transformation changed the way you operate? And how are you leveraging new technologies?
Amanda Hoertz [00:08:31]:
That’s a great question. Starting with things like a LIMS (Laboratory Information Management System) and an ELN (Electronic Laboratory Notebook), we’ve been rolling those out.
Hamlin is our largest site, so it’s always going to be the slowest to adopt new technologies. Right now, we have LIMS operating at our non-GMP sites and at two smaller GMP sites—our Boulder site (microbial) and our Geneva site (mammalian).
We are implementing LIMS across the network. As you’d imagine, we have over 650 active stability studies. Bringing those in from a paper-based system to electronic will take time, so we’re triaging and doing it incrementally. Our target is to be fully transitioned by the end of 2025.
That shift allows us to instantly understand statuses, compile data for clients, and track things in a much more robust way. We’ve had a very successful paper system, but paper can be damaged or lost. Electronic systems, when backed up properly, cannot. Same story for the ELN system—it’s already in place at our GMP and non-GMP site in Boulder, and at our non-GMP mammalian sites, and now we’re bringing it into our GMP mammalian sites.
It will allow us to link everything faster. Right now we already provide all raw data to clients, but it’s literally scanned pieces of paper. Soon, we’ll be able to deliver it in fully electronic format, searchable and linked—much more efficient.
Finally, at our non-GMP site we’ve implemented a lot of automation. Tecan systems are huge. For example, Derek Ryan, our Senior Director of Analytical Development in the mammalian network, and his team rely on them to process the hundreds and thousands of samples needed for PD on a regular basis.
We tried implementing a Tecan at our GMP site, but the complication was that the audit trail is essentially code—not straightforward for compliance. So Derek’s team tested alternatives in the non-GMP space. They pulled in the Waters Andrew+ pipetting systems. While they’re not using them with GMP audit functionality in development, they do have validated GMP audit trails.
So we purchased those for our GMP sites. The Waters Andrew+ systems take away all the repetitive pipetting from analysts. That improves consistency, reduces deviations and investigations, and allows analysts to set up ELISAs, dilution series, everything, and then just pop plates into the reader. Crucially, it has a clear GMP audit trail that reviewers can audit and understand. That’s a huge advancement.
On top of that, at KBI we have a very large amount of formulation development data. We’ve started to put that into a database and are using machine learning to see how we can predict formulations. For example, if a client needs a quick formulation—not fully optimized because of limited time or budget—we want to be able to set them up with the best possible chance of success.
All of these are works in progress, but it’s an exciting time. We’re adding efficiency and reducing some of the manual workload our analysts face.
David Brühlmann [00:11:57]:
Speaking of success, Amanda, what would you say are some best practices you follow to accelerate the path of ADC development? And what is core to your company culture that enables that?
Amanda Hoertz [00:12:11]:
We definitely look at each molecule individually, but with the experience behind us. As I mentioned, our tenure is a huge advantage. We remember the molecules that are similar. There are a number of biosimilars where it’s not the first time they’ve come to KBI, so we know where to start, and that helps us accelerate for later clients.
Same thing with ADCs—if we know what molecule or method is going to be the trouble spot (for example, charge heterogeneity), we start there in method development.
We also have a team, where after method development, they immediately start with method qualification. We have a number of platform approaches where we begin, and then we follow the molecule because it can always be different. But we understand where to start and what levers to pull—whether that’s improving resolution, improving a separation, or refining the method.
We make sure the method fully develops—whether that means resolving charged species, separating HMWs (high molecular weight species), or ensuring the peptide map is truly resolved.
We once had a client come to us with a charge method that showed only a single peak. They loved it, but we had to explain: if you’re not separating anything, the method has no value. We then showed them what could actually be separated with that method. They didn’t love seeing more than one peak, but for a method to be meaningful, it has to actually resolve species.
David Brühlmann [00:13:33]:
That’s a great example.
Amanda Hoertz [00:13:37]:
They didn’t like that very much, but we got them to where they needed to be.
David Brühlmann [00:13:40]:
I know, I know. It reminds me of some conversations I had in my career. I’d say technological advancements are not always welcomed, let’s put it like that. I’m not going to name names.
Amanda Hoertz [00:13:51]:
No, exactly. We want to understand—because that’s how the differences between batch one and batch two may be explained. If you see a difference in performance, you want to understand why. And as the industry continues to evolve, we may see different things. We may achieve better separation, we may now understand what the differences are. And we have to accept that.
David Brühlmann [00:14:13]:
Yeah, definitely. And there’s a lot going on, the industry is evolving. So what is your vision for the future of ADCs and biologics development in general? What trends do you see?
Amanda Hoertz [00:14:25]:
It’s really exciting—and I love it for patients. Having more targeted therapies and more options is huge.
We saw this in the early days with biologics—early IgG1s and IgG2s required much more customization to understand what you were doing. Now, many of those approaches are platforms. As we continue to see more ADCs produced, we’re going to get more comfortable with how to manufacture them efficiently, cost-effectively, and how to identify winners and losers faster. That’s huge.
KBI right now has the ability to test non-cytotoxic ADCs at all of our sites, and cytotoxic ADCs analytically at two of our sites. What we’re investing in is another U.S.-based lab where we can test GMP cytotoxic ADCs safely within the mammalian network—covering both process development and analytical development.
That’s going to require significant capital investment, since handling large amounts of toxic payload requires specialized facilities. We’re still determining whether to partner with clients for GMP production through a vendor or to build those capabilities fully in-house. But we see this as the next frontier, and we’re making those investments to grow with the industry.
Given our experience with niche molecules and with ADCs, I think we’re in the right position to maximize the benefit for patients.
David Brühlmann [00:15:47]:
So, you’ve built a successful career leading a team of 300 people. What advice would you give biotech scientists looking to excel in complex modalities like ADCs—and also in managing large, cross-functional organizations that aren’t all at the same site?
Amanda Hoertz [00:16:07]:
For managing a site this large, it all comes down to having the right people working for you and with you. There’s no way I could directly handle all the issues that can come up with 300 people. My direct reports need to be empowered to handle things, and then we triage as issues move up and down. That’s critical.
For building a successful career: people don’t love change, but change is part of what we do. My job has changed over the years, the industry has changed over the years. Absorbing information and being willing to move with what’s hot and what’s emerging in the market is important.
ADCs can be intimidating. There are plenty of drugs that don’t have toxic payloads, that are easier and lower risk. But this is where the industry is going. We need to find ways to develop them safely and successfully—for both patients and employees. So being nimble and willing to move with the market is critical.
When I came to KBI, I only intended to stay for two years. But I was in the right place at the right time, opportunities came up, and I took them. I don’t think there was a master plan. And I think many of my colleagues at KBI have had similar experiences—as the company grew, opportunities appeared, and it’s been a great place to be. I don’t know if that kind of growth can be planned or replicated—it just comes down to being willing to do what’s needed to make the company successful.
David Brühlmann [00:17:41]:
Well, this has been great, Amanda. Thank you so much for sharing your passion and insights. What would you say is the most important takeaway from our conversation?
Amanda Hoertz [00:17:51]:
I think the most important takeaway is that ADCs are an exciting new therapy, and they represent a significant improvement on existing therapies—providing patients better outcomes with fewer side effects.
There’s such a rich pipeline in the industry right now, and being able to adapt and characterize these biologics is the next challenge. We’re looking forward to being part of that solution for the industry. Thanks so much for taking the time to talk with me today—I really appreciate it.
David Brühlmann [00:18:12]:
That’s fantastic. Amanda, where can people get a hold of you?
Amanda Hoertz [00:18:16]:
The KBI website is a good place. There’s also our dedicated portal, https://standalone.kbi.bio/, which allows you to get quick quotes, ask questions—it’s very interactive and easy to use. We jokingly call it the “Domino’s Pizza Tracker” for biotech, because you can submit a request and then see exactly where it is in the process.
David Brühlmann [00:18:33]:
Excellent. I’ll leave all the links in the show notes so listeners can find them easily. And once again, Amanda, thank you so much for being on the show today. It was a huge pleasure.
Amanda Hoertz [00:18:43]:
Thanks, David. I appreciate it. Bye.
David Brühlmann [00:18:46]:
What a fascinating conversation with Amanda Hoertz. Her insights on ADC development, analytical strategies, and leadership are invaluable for any biotech scientist.
Please leave us a review on Apple Podcasts or whatever platform you found us on. It helps other biotech scientists like you discover the show. I thank you so much already - and I love hearing from you. So thank you very much for tuning in today. Stay tuned for part two where we'll dive into the analytical complexities of ADCs.
For additional bioprocessing tips, visit us at Smart Biotech Scientist Podcast - Master Bioprocess Development. 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
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About Amanda Hoertz
Amanda Hoertz is the Vice President of Analytical and Formulation Sciences (Mammalian Network) at KBI Biopharma, where she leads a team of more than 300 analytical scientists. Her organization supports method development, verification, qualification, validation, formulation design, forced degradation studies, characterization, and stability testing across preclinical to commercial-stage biopharmaceutical products.
With over 14 years at KBI, Amanda brings deep expertise in analytical strategy and biopharmaceutical development. She earned her Ph.D. in Chemistry from Duke University and holds additional academic experience from Johns Hopkins University and the University of Pennsylvania.
Connect with Amanda Hoertz 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.
Hear It From The Horse’s Mouth
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Antibody-drug conjugates (ADCs) are generating serious buzz in biotech corridors, offering a precision-guided missile against cancer while minimizing collateral damage. But the path from concept to clinic is far from straightforward—especially when the molecule itself bends the rules of traditional bioprocessing.
In this episode from the Smart Biotech Scientist Podcast, David Brühlmann welcomes Amanda Hoertz, Vice President of the Analytical and Formulation Sciences department for the Mammalian network at KBI Biopharma. With oversight of 300 scientists and deep expertise in taking the world's most complicated biologics to market, Amanda has spent her career at the intersection of scientific rigor and patient impact. Her approach goes far beyond cookie-cutter platforms, focusing instead on ground-up problem solving for complex modalities—including some of the trickiest ADCs in the pipeline.
A lot of clients, whether it's ADC or not, they're in the FIH stage. They need to understand whether or not they have a product where they're going to invest tens of millions of dollars into it. So they need to know: is it efficacious, is it manufacturable, is it stable, what can we do with it? And that way they can get through their tox studies and their phase one and then understand if they have the money to invest to go further.
So, information that can be calculated theoretically - pI, molecular weight - those can be done just based on the sequence. But any hands-on data you have - because as you know, proteins fold differently - a theoretical pI and an observed pI can be different.
David Brühlmann [00:00:40]:
Welcome to The Smart Biotech Scientist. I'm David Brühlmann, your host, and today we're diving deep into the fascinating world of antibody-drug conjugates with Amanda Hoertz, who's a Vice President of Analytical and Formulation Sciences at KBI Biopharma. Amanda leads 300 analytical scientists across KBI's mammalian network, tackling some of the most complex challenges in biologics development.
We'll explore her journey from chemistry PhD to industry leader and discover what makes ADCs both incredibly powerful and uniquely challenging to develop. Let's dive in.
David Brühlmann [00:02:35]:
Welcome, Amanda, to The Smart Biotech Scientist. It’s good to have you on today.
Amanda Hoertz [00:02:38]:
Hi David. Thank you for having me. I appreciate it.
David Brühlmann [00:02:43]:
It's a pleasure, Amanda. Share something that you believe about bioprocess development that most people disagree with.
Amanda Hoertz [00:02:51]:
This question makes me nervous, but I'll shoot for it because I don’t pretend to know what everyone else thinks. I think one thing that a lot of people believe is that you can adapt almost any biologic to a single platform. And I think the different classes of molecules and formats need to be considered and need special considerations.
I think we can benefit from a lot of the historical data and the potential power of machine learning to reduce de novo data generation. But a lot of these determinations are empirical and have to be done for that specific molecule.
David Brühlmann [00:03:21]:
That's an excellent point. There's definitely a lot of specificity for each molecule. Before we talk about ADCs, Amanda, let's talk about yourself because you've built an impressive career leading 300 scientists across KBI's network. So tell us how you got started in chemistry, in the pharmaceutical/biotech industry, and what were some interesting pit stops along the way.
Amanda Hoertz [00:03:48]:
Sure. I love science. I love the logical portion of it and how you can understand something and do an investigation and rule out factors. And, funnily enough for my poor family, it’s become part of my actual personal life. I think about things in a very analytical way, similar to an investigation we do at work.
My initial love of chemistry actually came from when I was in high school. My chemistry teacher was a PhD from Berkeley, which was obviously atypical for a high school chemistry teacher. And she had very, very high standards. She’d put us all at the board and we’d be so afraid of being wrong in front of the whole class that it was my major focus to make sure I understood those concepts the best - because that was my nightmare.
In seventh grade, I also became a type 1 diabetic. And it was so impressive to me that this little bottle of clear liquid - when you had such a small injection of insulin - could make you feel dramatically better or worse. So those things together really pushed me in the science direction.
When I was in undergraduate and graduate school, I worked on antibiotic resistance and understanding how we could modify those genes to try to make novel analogs of currently approved drugs and counteract antibiotic resistance, and to make those in a scalable, economic way. That pushed me towards industry.
What I loved about industry was that the work I did in academia was very conceptual and I didn’t really see it being applied in the short term, whereas the work I do at KBI is going into clinics, it’s being used now. Some of them fail, but I see it being realized. I see people getting the benefit, especially as KBI has matured. We’ve had a number of products that started out preclinical and now are commercial. We see the benefits, we see people taking these drugs. And it’s not just a concept that maybe 20–30 years from now it might happen — it’s actually happening. We know people are getting benefits. It’s a great feeling.
David Brühlmann [00:05:47]:
Now, specifically, you're now working in Analytical and Formulation Sciences. What excites you most about working in this very part of biotech today?
Amanda Hoertz [00:06:00]:
There are just so many different options coming forward for patients. We're on the cutting edge. We get to see all the different treatments, and as I said before, some of them fail. And that's a natural part of the industry. But we see how people are innovating their thought process, what different drugs can possibly be offered to patients.
And as we see them getting more and more specific, especially with something like ADCs, we see less side effects, we see patients getting improved options. And it's very exciting to be part of that and to see it being realized.
David Brühlmann [00:06:32]:
I'm very excited to talk about ADCs, because it's a huge trend in our industry - no doubt about that. A lot of people are developing ADCs, but tell us why they are such powerful therapies before we dive into the nitty-gritty of ADC development.
Amanda Hoertz [00:06:49]:
Sure. I mean, there is a payload attached to the antibody, and that can be either non-cytotoxic or cytotoxic. Obviously, the more potent ones are harder to handle. But they are allowing us to take cytotoxic drugs that in general couldn't be administered to a patient, and target them specifically for the tumor.
So by using this basically directing antibody, you're able to get those cytotoxic drugs directly to the tumor. And because we have less of the bystander effect - which is where cells that are nearby are also impacted in the cell death - it's more targeted.
General chemotherapy that started out a long time ago would only target rapidly dividing cells. So that would target other things that aren't part of the target and would result in things like hair loss and nerve damage. By being able to target these with ADCs, we're able to really just target the tumor and we're able to have these ADCs and immunotherapies really be a very specific treatment for the cancer drug.
David Brühlmann [00:07:46]:
And what makes ADC development very challenging compared to traditional monoclonals?
Amanda Hoertz [00:07:54]:
The same thing that’s a benefit is the same thing that makes it very challenging. So, at KBI we’ve worked on and manufactured many non-cytotoxic ADCs. Where it becomes really challenging is when you start working with the cytotoxic payloads.
Those, in very small amounts, are designed to kill cells. Therefore, there's a safety risk for the employees handling them for testing, and handling them for manufacturing. The biggest risk is obviously with the free payload.
Analytically, we handle that very carefully. We only need that for really one assay - the free drug - where we have to run a standard curve of the free drug and then run the actual sample to see how much has been released. But handling that free drug to be able to run that standard curve is the risk to our employees, and to any employee that would then service that instrument.
Conversely, in the process development and manufacturing space, they would need to handle an even larger amount of that payload to be able to conjugate it to the actual product. And so those are the highest risks. Making sure that we have the right safety protocols so that we are not exposing our employees to any of these deleterious effects - which are by design for the cancer cells, but not by design for the general population - is critical.
David Brühlmann [00:09:03]:
Can you give us just a high-level view of how ADCs are actually produced? I mean, you have quite a puzzle: you have the antibody, you have the linker, you have the payload. What’s the general sequence, especially for people who might not be familiar with ADC development?
Amanda Hoertz [00:09:19]:
Many ADCs are developed before they come to KBI, but for some we’re involved from the beginning. There’s an antibody - typically one that’s already well understood - and companies will modify the amino acid sequence to target the specific locations where the linkers can bind to then get that payload attached.
By modifying how the molecule is formed, you're able to target specific numbers of attachment sites and specific amounts of that cytotoxic payload. It is very important that we have the analytical tools to look at both the antibody, the free linker, and the free payload. The more stable that is, the better.
Obviously, we want it to conjugate, and then we want none of the free linker to be showing up. The free linker tends not to be a problem - it's just a sign that we're actually losing some of the payload. The payload obviously is a problem if we have high amounts of free payload.
So we develop analytical tools to monitor that over the course of stability under many stresses, and understand whether or not agitation stress, freeze–thaw stress, temperature stress, duration of stress, or chemical stresses - including acidic, basic, and oxidative - are influential in either damaging the linker or releasing that payload.
That’s the function of our stability studies: to quantify the amount of free payload that gets released. It's also impactful if we don't have payload attached, because then the drug is not efficacious.
So usually it’s the free payload that ends up being the problem, because in small amounts it's impactful. But we also want to make sure that the drug we're delivering still has that payload attached.
David Brühlmann [00:10:53]:
Let's make this practical. Let's assume I'm a CEO of a biotech company and we are developing an ADC and we're coming to you, to KBI. What are the first critical questions your team would ask my company to set up our analytical strategy for success?
Amanda Hoertz [00:11:09]:
One of the things that's great about KBI is that we're bespoke services: we offer what you need. A lot of companies have a platform approach: you give them this amount of material, or they produce this amount of material, and then they do these fixed experiments.
What we do is take in the information you have. So if you were coming to me with an ADC that you want to develop, I would want to understand what information you already have. What do you understand about the molecule? What can we leverage from historical data? And then we would set up, based on your timeline and your budget, what we can further investigate to get you to the next stage.
A lot of clients, whether it's ADC or not, are in the FIH stage. They need to understand whether or not they have a product where they're going to invest tens of millions of dollars into it. So they need to know: is it efficacious, is it manufacturable, is it stable, what can we do with it?
And that way they can get through their tox studies and their phase one, and then understand if they have the money to invest to go further.
Information that can be calculated theoretically - pI, molecular weight - those can be done just based on the sequence. But any hands-on data you have, because as you know, proteins fold differently, a theoretical pI and an observed pI can be different. That data helps us maximize your timeline and your budget.
David Brühlmann [00:12:23]:
You said that one thing that sets you apart is offering bespoke services. Because choosing a development partner or a CDMO can be quite overwhelming. So why should I, as this fictional CEO, choose KBI? Or why should I go to another CDMO? What are some decision parameters I should consider?
Amanda Hoertz [00:12:45]:
If you're looking for an IgG1 - a very “vanilla” antibody - you probably don't need the services of KBI.
KBI has a very high advanced-degree rate. We are very good at complex molecules. Our experience includes bispecifics, conjugated molecules - the list goes on. But we are going to be more expensive than the Lonzases or Thermos of the world.
So if you just need an antibody produced, that’s going to be your better path. But if you need something that has nuance, that requires more thought and more experimentation - that’s where KBI fits into that niche market with bespoke services.
We’re not going to compete with the huge WuXis of the world. But what we do bring is the experience you need to make your complicated molecule successful.
We’ve had a number of clients that request RFPs from KBI and then come back to us saying our proposals are more expensive. They go to a cheaper CDMO, and then later we get them back. By then they’ve sacrificed part of their budget and had a failure at a more platform-based CDMO. They’ve also sacrificed six or seven months of their timeline to figure that out.
So, for that theoretical CEO, the key is knowing how complicated your molecule is and whether you need the nuance we offer.
Our batch success rate for fiscal year 2024 was 93%, and we don’t do engineering runs. We put in place upfront the cell line, the analytical, and the process development engine, so that by the time we’re making it at the scale of 2,000 liters, you actually get a product successfully.
David Brühlmann [00:14:21]:
Let’s talk about the analytical puzzle. Because there’s a lot going on: we’ve got the antibody, the linker, the payload. We need all kinds of different analytical methods. So tell us your approach - how do you develop methods to characterize each component? Because at the end of the day, you need a sophisticated process control to ensure you’re actually getting the very ADC you want to develop.
Amanda Hoertz [00:14:46]:
Yes, there are a number of compendial methods that are standard for any antibody. We also have product quality methods — your classic SEC, where we need to understand the HMW. You want to keep aggregates low. That’s not specific to ADCs versus non-ADCs.
Where it gets specific for ADCs is in the characterization of the free payload, the free linker, and the charge heterogeneity. That’s usually where we see the most nuance required, both with cytotoxic and non-cytotoxic ADCs.
There seems to be more of a development challenge for the iCE or IEX methods we run. We see shifting profiles, we see inconsistency in achieving good separation. For example, in iCIEF, having the right blend of pharmalytes and the right handling conditions is critical to get us from the development stage, to the qualification stage where we’re generating GMP data, and then to the validation stage where we can execute this across multiple sites and multiple analysts. It has to be robust.
That’s the biggest challenge I’ve seen. The free payload tends to be a pretty straightforward reverse-phase method where we’re just titrating against a standard curve.
It’s the charge heterogeneity that keeps me up at night.
David Brühlmann [00:15:59]:
And what are the things you can do even upfront, before we would even come to KBI or another development partner? Are there some strategic choices companies should make to avoid, for instance, these headaches? I mean, I know there's a lot of complexity, but are there maybe some early decisions that simplify or reduce the complexity?
Amanda Hoertz [00:16:21]:
I think a lot of it is understanding your linker attachment sites. The most successful conjugated materials we’ve made are those where both the conjugation sites and the post-translational modifications that may influence them are very well understood.
We have a dedicated mass spec team. For example, we can produce forcibly degraded material so they can understand how it’s going to degrade, and at the molecular level identify which sites are prone to modification. Then we can actually monitor that.
For example, oxidation or other modifications can be identified through detailed peptide mapping. That allows us to pinpoint individual peaks, and when we see a peak grow, we understand what’s happening.
Peptide mapping requires some upfront development - for instance, recognizing that when this site gets oxidized, a shoulder or a peak appears. But once we’ve identified what each peak represents, we can monitor them in a much more streamlined and cost-effective way over the product’s lifetime.
David Brühlmann [00:17:20]:
You mentioned that the linker is very important, and I also imagine the conjugation method. So can you tell us what is the state of the art today? Because I mean, a lot has happened in the last few decades in ADC.
Amanda Hoertz [00:17:35]:
There are a number of ways to conjugate. Most commonly, thioethers, disulfide bonds, and peptides are used and they’ve been very successful.
Having specific attachment sites, like I said before, is also critical. You don’t want random attachment. That was the approach for the early ADCs, where we were hoping for the best and aiming for a certain amount of payload attached.
The actual conjugation decision-making is a little bit out of my expertise. I usually deal with the molecule after the payload is attached, and how we can understand its properties. But of course, how those decisions are made also has a direct impact on efficacy. You want to make sure none of the sites critical for binding are blocked.
We continue to refine as we learn. The ADC market is going exponential. There are 12 approved ADCs, but we’re aware - and the market is aware - of hundreds more in development. A lot of those won’t make it, but once a platform is successful, it can often be applied multiple times. So when a client has one success, that client usually has a higher rate of success in follow-on programs.
David Brühlmann [00:18:39]:
Now let’s talk about formulation, because that’s also quite a challenge. An antibody by itself is quite well managed, but probably more complex modalities pose extra issues. How does that play out for an ADC? What are the challenges, and what approaches have you developed as a team to tackle formulation challenges?
Amanda Hoertz [00:18:58]:
Absolutely - that is definitely a component. We need to develop a formulation for the drug substance intermediate (DSI), which is the pre-conjugation material. That formulation can’t inhibit the conjugation reaction. So we need to be careful: no surfactants, no small molecules that could interfere.
Our classic approach at KBI is to design a very simple formulation that is stable to freeze–thaw. Buffers and excipients can shift during freeze–thaw, and we don’t want to damage the biologic during that process. That’s critical for the DSI as it moves into DS production.
Once the product is conjugated, it’s more typical for us to include a small amount of surfactant to reduce stress from agitation and freeze–thaw, and to add excipients that increase stability.
The gold standard for biologics is 24 months of stability at 2–8 °C. So our goal is to design formulations - with appropriate excipients - to achieve that. But at the DSI stage we must be very cautious: no surfactants, minimal excipients, so that nothing interferes with conjugation.
David Brühlmann [00:20:03]:
And for those who are not familiar with ADCs - the DS formulation is important because certain companies are not able to produce the antibody and then do the conjugation at the same site. So there’s some shipment involved, right?
Amanda Hoertz [00:20:19]:
Exactly. For non-cytotoxic drugs, at KBI we are able to produce the DSI and then conjugate it to generate the DS. That is then typically shipped to a fill–finish facility for DP (drug product) manufacturing, which usually involves filtration and filling operations.
For cytotoxic ADCs, KBI currently does not offer the conjugation. So we generate the DSI, then ship it to another site for conjugation, and then onward to a different site for DP production, depending on the vendor.
The less handling required once it’s conjugated, the better. Every operation increases the risk of damaging the payload, damaging the product, and also increasing risk to employees.
So, our approach is to maintain a pH that is acceptable, with minimal excipients and no surfactants at the DSI step, so that stabilizers can be added later once it’s conjugated. Then the DP step is usually just filter, fill, and finish.
David Brühlmann [00:21:20]:
I got you. So you have a formulation for your DSI, you do the conjugation, and then you add whatever is needed to stabilize your molecule, right?
Amanda Hoertz [00:21:30]:
Exactly.
David Brühlmann [00:21:31]:
It makes sense.
Amanda Hoertz [00:21:32]:
The DSI and the DS are typically frozen formulations. That needs to be taken into consideration. The DP is typically stored at 2–8 °C. That’s the most financially successful option for companies when shipping to clinics - everyone has a refrigerator.
Once you start requiring storage at –20, –50, or –75 °C, you face challenges: do clinical sites have those freezers, and do you need to supply them to each site?
David Brühlmann [00:21:59]:
And to what extent are the DS and DP formulations for an ADC different from a standard mAb, or are they quite similar?
Amanda Hoertz [00:22:07]:
They are quite similar. It’s difficult for us to include a surfactant, although as I said, it reduces agitation as well as freeze–thaw impact. Depending on the molecule, we might need to add other stabilizers, like arginine, to reduce aggregation.
The pH is obviously critical. Different buffers can be more or less successful, and that’s generally determined empirically. Of course, we have targets based on the pH values we’re looking at, and that’s largely a function of the molecule’s isoelectric point (pI). So it’s also important to assess whether the linker or the payload impacts the overall pI.
David Brühlmann [00:22:42]:
That wraps up part one of our conversation with Amanda Hoertz. We’ve explored her remarkable journey and the exciting world of ADC development.
Please leave us a review on Apple Podcasts or whatever platform you found us on. It helps other biotech scientists like you discover the show. I thank you so much already - and I love hearing from you. So thank you very much for tuning in today. Stay tuned for part two where we'll dive into the analytical complexities of ADCs.
For additional bioprocessing tips, visit us at Smart Biotech Scientist Podcast - Master Bioprocess Development. 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
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About Amanda Hoertz
Amanda Hoertz is the Vice President of the Analytical and Formulation Sciences department for the Mammalian network at KBI Biopharma. She oversees a network of 300 analytical scientists who execute method development, verification, qualification, validation, formulation development, forced degradation, characterization, and stability testing for preclinical to commercial products at the CDMO.
She has been at KBI for 14.5 years and prior completed her Ph.D. in Chemistry at Duke University. Her undergraduate and other academic experiences include Johns Hopkins University and the University of Pennsylvania.
Connect with Amanda Hoertz 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.
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 too long, biotech innovators have viewed biological systems as inherently messy, unpredictable, and full of “black box” mysteries. But what if, armed with the latest digital tools, AI, and cross-disciplinary thinking, you could transform bioprocessing from a series of trial-and-error experiments to a streamlined, proactive design process?
This is the second part of a conversation between David Brühlmann and Carmen Jungo Rhême, a professor at the University of Applied Sciences in Fribourg, Switzerland, and director of the Biofactory Competence Center (BCC). They discuss how digital tools, real-time data modeling, and artificial intelligence are transforming bioprocess development—and shifting our perspective from viewing biology as unpredictable to seeing it as something designable and controllable.
With the tools we have today—particularly digital tools, real-time data modeling, and AI—we can understand and control biology in ways that were unimaginable just a few years ago. If we shift our mindset from “biology is messy” to “biology is designable,” it changes everything. I think it opens the door to more robust and faster process development, leading to quicker innovation and truly sustainable solutions. This mindset shift—from reactive to proactive, or from trial-and-error to design-and-control—is what will define the future of the biotech industry.
David Brühlmann [00:00:51]:
Welcome back to part two with Carmen Jungo Rhême, who is a professor at the University of Applied Sciences in Fribourg, Switzerland, and director of the Biofactory Competence Center.
If part one inspired you about fighting superbugs and sustainable food production, you’ll love this deep dive into the Biofactory Competence Center’s revolutionary approach.
We’re exploring how their non-classified cleanrooms seamlessly transfer to GMP facilities, their practical idea-to-scalable-process methodology, and the critical skill gaps Carmen has discovered while training both newcomers and industry veterans.
Ready to discover what makes bioprocess development truly scalable? Let’s dive in.
Now, let’s talk more specifically about what you’re doing at the Biofactory Competence Center. You’re a professor at the University of Applied Sciences in Fribourg and also leading the Biofactory Competence Center. We’ve mentioned that term several times already. Tell us a bit more — what is this center all about? What’s your mission, and what specific challenges and needs are you addressing?
Carmen Jungo Rhême [00:03:13]:
At the Biofactory Competence Center, our main goal is to work in collaboration with industrial and academic partners on applied research projects.
Universities typically focus on fundamental research, while universities of applied sciences, like ours, focus more on applied research. We collaborate with startups as well as larger companies — mainly in biotechnology, including the pharma and food industries.
On top of that, we also offer training for our students — practical training and theory in bioprocess engineering — and for professionals from industry, typically in upstream and downstream processing, as well as other skills such as aseptic techniques.
David Brühlmann [00:04:15]:
Let’s assume I’m the CEO of a startup company with a new technology or idea, and I need a development partner like your center. How does this process work? We come to you and say, “Hey, we have this amazing idea to solve antimicrobial resistance.” What happens next?
Carmen Jungo Rhême [00:04:40]:
Each project is different, but we always follow a structured approach. When a biotech company — large or small — comes to us with an idea, we start by listening and understanding their concept, goals, and challenges.
From there, we typically guide them through four key phases:
This is the general framework we follow.
David Brühlmann [00:07:00]:
Speaking of scale-up — when transferring to another partner, CDMO, or in-house facility — what are the typical scales you work at in your facility, and at what point do you transfer?
Carmen Jungo Rhême [00:07:20]:
We typically work with 5-liter bioreactors, which can mimic very well a 15,000-liter system. Most of our development studies are performed at 5-liter scale. We also have 50-liter bioreactors, but we often focus on the 5-liter scale because scale-up can be done directly to much larger systems — 1,000 or even 15,000 liters. This is quite common in the industry. You often lose too much time moving through intermediate pilot scales before final manufacturing.
David Brühlmann [00:08:00]:
Exactly — especially with digital tools and modeling, if your small-scale system is well-characterized, you should have everything you need to scale directly and succeed.
Carmen Jungo Rhême [00:08:14]:
Yes, definitely.
David Brühlmann [00:08:16]:
At the Biofactory Competence Center, you both co-develop with companies and train people for GMP or lab work. Tell us more about your training programs and the skill gaps you’re addressing.
Carmen Jungo Rhême [00:08:42]:
We offer operator training for the pharmaceutical industry. Over the last ten years, many facilities were built in Switzerland, and the industry had to hire a large number of operators. That’s why this training was created — to prepare competent people for GMP operations. It’s a five-week program covering GMP documentation, lab practices, pH and conductivity measurement, gowning, and more. For more advanced professionals, we also offer three-day trainings — one in upstream processing and one in downstream processing.
David Brühlmann [00:09:47]:
And those advanced trainings — are they GMP-focused or more technical?
Carmen Jungo Rhême [00:09:58]:
They’re more technical and scientific, not focused on GMP. For example, in the upstream course, we cover mass balance, calculating specific growth rates and doubling times, and determining feed rates for fed-batch cultures. So yes, more technical than regulatory.
David Brühlmann [00:10:25]:
You train university students and industry professionals, while the industry itself is changing rapidly — robotics, AI, digitalization. What do you think will be the top three skills that matter most in five years?
Carmen Jungo Rhême [00:10:54]:
That’s a good question. Many skills are important, but I’d highlight three:
This broader view is essential.
David Brühlmann [00:12:28]:
Absolutely. Systems thinking is often overlooked, yet it’s fundamental. In a connected world, being able to “connect the dots,” as Steve Jobs would say, helps professionals stand out and even turn their data into valuable assets.
Carmen Jungo Rhême [00:13:11]:
Exactly. Data is key — and systems thinking helps you use not only process data but environmental data, too.
David Brühlmann [00:13:25]:
You’ve been leading the Biofactory Competence Center for about a year and a half. What’s your vision for the next few years?
Carmen Jungo Rhême [00:13:56]:
In the coming years, I want to continue working on antimicrobial resistance — it’s a major global challenge. We’re collaborating with a Swiss startup, Micreos, based in Baden, where we express and purify endolysins to fight Staphylococcus aureus. I’m also passionate about sustainable food production, especially in Switzerland. Using waste products efficiently and combining them with digital tools to maximize data and outcomes is one of our goals.
And, of course, continuing to deliver impactful training for students and professionals — and learning from them in return — helps us keep improving.
David Brühlmann [00:15:30]:
Switzerland has always adapted quickly — to environmental, industrial, and now technological changes. What kind of mindset shift do you think we need as scientists moving forward?
Carmen Jungo Rhême [00:16:08]:
We need to stop seeing biology as unpredictable. For too long, biological systems have been treated as black boxes — mysterious and variable. But with digital tools, real-time data modeling, and AI, we can now understand and control biology in unprecedented ways. If we shift our mindset from “biology is messy” to “biology is designable,” it changes everything — enabling more robust, faster, and more sustainable processes.
This shift, from reactive to proactive and from trial and error to design and control, will define the future of the biotech industry.
David Brühlmann [00:17:21]:
Before we wrap up, what important topic haven’t I asked about that you’d like to share with our biotech community?
Carmen Jungo Rhême [00:17:30]:
We also have projects in digital transformation.
For example, we’re collaborating with DataHow and Beckman Coulter on a project funded by Innosuisse’s Innovation Booster. The goal is to demonstrate how digital technology and AI are transforming biotech.
The project focuses on optimizing green fluorescent protein (GFP) production in E. coli fed-batch cultures. We run design-of-experiment studies using Beckman Coulter’s BioLector XT micro-bioreactor system — a high-throughput platform that allows many experiments in parallel.
All process data is collected and used by DataHow to build a digital twin — a hybrid model to identify optimal process conditions quickly. It’s both a research and educational project: our students learn to use digital twin tools so they can apply them in industry.
David Brühlmann [00:19:40]:
Fantastic — I love this project. With everything we’ve discussed today, what’s your 22nd takeaway?
Carmen Jungo Rhême [00:19:54]:
Bioprocessing today isn’t just about managing complexity — it’s about mastering it. With the right mindset, tools, and training, we can turn biological variability into predictable, scalable, and sustainable solutions. Whether it’s fighting antimicrobial resistance, transforming food systems, or embracing digitalization — the future of biotech is about integrating the right tools for smarter bioprocessing.
David Brühlmann [00:20:38]:
Thank you so much, Carmen, for sharing your passion and expertise. Where can people connect with you?
Carmen Jungo Rhême [00:20:49]:
People can connect with me on LinkedIn or through the Biofactory Competence Center website — there’s an email address for inquiries or collaborations.
David Brühlmann [00:21:08]:
That’s great. I’ll leave all the information in the show notes. Thank you once again, Carmen, for being on the show today.
Carmen Jungo Rhême [00:21:31]:
Thank you very much, David. It was a pleasure.
David Brühlmann [00:21:34]:
Fantastic insights from Carmen Jungo Rhême on the future of bioprocess development and training — from seamless GMP transfers to essential skills for the next five years.
Remember, scaling doesn’t have to be overwhelming. If you need guidance on your process or technology development journey, schedule a free consultation at Brühlmann Consulting.
Thank you for tuning in — please leave a review 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. For more tips, visit smartbiotechscientist.com and stay tuned for more inspiring biotech insights. Until next time — 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
🧬 De-risk CMC development and get decision-making guidance with a new AI platform that transforms CMC overwhelm into predictable development success (launching early 2026). Join the waitlist here: https://david-jkhjdoje.scoreapp.com
About Carmen Jungo Rhême
Carmen Jungo Rhême is full professor at the Haute Ecole d’Ingénierie et d’Architecture de Fribourg (HEIA-FR) and Director of the Biofactory Competence Center (BCC). She has extensive experience (17 years) in the pharmaceutical industry with a proven track record in several biopharmaceutical companies manufacturing therapeutic recombinant proteins (Lonza, Merck Serono, UCB Farchim and CSL Behring).
She specialized in bioprocess development, both in cell culture and in purification of proteins, scale-up, and technology transfer of marked products. Since her start at HEIA-FR in November 2023, C. Jungo Rhême has initiated several research projects in the field of antimicrobial resistance, one of them in the field of antimicrobial resistance, sustainable food production, and digitalization of bioprocesses.
Connect with Carmen Jungo Rhême 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.
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
Almost every corner of modern medicine and sustainable food production today is facing a massive challenge: how do we outpace drug-resistant “superbugs” and create food for a growing population using fewer resources? The answer, it turns out, may come down to how well we understand and control the biomanufacturing processes underpinning these biomaterials and biomolecules.
In this episode of Smart Biotech Scientist Podcast, David Brühlmann speaks with Carmen Jungo Rhême, Full Professor at the University of Applied Sciences in Fribourg, Switzerland and Director of the Biofactory Competence Center.
With years in the pharmaceutical industry at Lonza, Merck Serono, UCB Farchim, and CSL Behring, she now tackles global challenges like antimicrobial resistance, sustainable food, and digitalization. From her beginnings in chemical engineering at EPFL to leading at the nexus of academia and industry, Carmen is helping shape the future of smarter, more robust biotech.
The emergence and spread of drug-resistant pathogens challenge our ability to treat common infections with existing antimicrobials such as antibiotics. The World Health Organization has identified antimicrobial resistance as one of the top global challenges for humanity in the coming decade. Currently, several approaches are being explored by the scientific community, including the development of new vaccines, monoclonal antibodies, phage therapy, and recombinant proteins like endolysins to combat difficult-to-treat bacteria. At the Biofactory Competence Center, we are collaborating with the University Hospital in Lausanne in the field of phage therapy.
David Brühlmann [00:00:56]:
Welcome back to the Smart Biotech Scientist. I’m your host, David Brühlmann, and today I’m thrilled to have Carmen Jungo Rhême with us. Carmen is a Full Professor at the University of Applied Sciences in Fribourg, Switzerland, and Director of the Biofactory Competence Center.
With years of experience mastering bioprocess challenges at Lonza, Merck Serono, UCB Farchim, and CSL Behring, she now tackles global challenges including antimicrobial resistance, sustainable food production, and digitalization. From fighting superbugs to revolutionizing scalable process development, Carmen’s insights will change the way you think about the future of biotech.
Welcome, Carmen, to the Smart Biotech Scientist.
Carmen Jungo Rhême [00:03:08]:
Hello David, it’s great to see you and to be here talking with you.
David Brühlmann [00:03:12]:
It’s a pleasure, Carmen. We’ve been planning this interview for a while, and now it’s finally happening. To start, could you share something you believe about bioprocess development that most people might disagree with?
Carmen Jungo Rhême [00:03:28]:
Many people perceive bioprocessing as highly uncertain and lacking robustness. However, when bioprocesses are thoroughly characterized—meaning they are well understood and effectively controlled—they can be extremely robust. A typical bioprocess includes both upstream and downstream parameters, sometimes managing over 200 variables. This complexity highlights the need for comprehensive process characterization, which I believe is essential for enhancing robustness and minimizing variability.
David Brühlmann [00:04:16]:
Absolutely. I couldn’t agree more. That’s very well said, Carmen. We have several things in common and I actually I still remember that many, many years ago when we started studying chemical engineering at the EPFL in Lausanne, Switzerland, we met already at that time and then later on in our career our path have crossed several times again. But actually I'm getting ahead of the story. I would like you to draw us into the story. Tell us Carmen, how you first got started in the recombinant protein world and what were some interesting pit stops along the way that led you to now your role as a professor and leading the Biofactory Competence Center?
Carmen Jungo Rhême [00:05:01]:
Yes, I remember first of all when we were studying at EPFL, and I really remember the first day I saw you attending the classes. I would not have imagined at that time that we would also work in the same company, actually at Merck Serono, and especially that we would stay in contact. It’s really a pleasure.
So how did I arrive at the BCC? First of all, I would like to mention that during my studies at EPFL, I studied chemical engineering. I was inspired by the elegance of recombinant proteins—how you can take a gene, express it in a host cell, and produce something with therapeutic or industrial value.
Then my journey through companies like Lonza, Merck Serono, UCB Farchim, and CSL Behring was key before joining the Biofactory Competence Center. For example, at Lonza, I was immersed in the world of large-scale recombinant protein production, learning how to transfer and scale up from lab scale to manufacturing scale. At Merck Serono and UCB Farchim, I continued to strengthen my know-how in technology transfer, scale-up, and starting up new facilities. Finally, at CSL Behring, I expanded my experience in R&D.
What is also important is that I was able to develop a network in the pharma industry before joining academia. I think this is key—to have industry contacts to initiate projects and to stay aware of what’s happening in the field. At the BCC, I can continue to innovate in collaboration with industrial partners, and I can also share my experience with students, who represent the next generation of pharmaceutical scientists.
David Brühlmann [00:06:59]:
You make an excellent point, Carmen. Obviously, along our careers we learn a lot about science, but it’s not only about science—it’s really about developing a network. And I think especially at the stage we are in our respective careers, the network becomes increasingly important for collaborations, research projects, and so on. So if you’re listening and taking notes, Smart Biotech Scientist, put this at the top of your list: develop a network. That’s very important.
Carmen Jungo Rhême [00:07:32]:
Yes, I completely agree with you. That’s really key for your career—to develop a strong network. And often, when you have a question or a bigger challenge, you will go back to your network, and maybe someone will help you. You can do a lot of things with your network.
David Brühlmann [00:07:49]:
And I’ve heard some people say that your network is your net worth.
Carmen Jungo Rhême [00:07:54]:
Yes, I think that’s true.
David Brühlmann [00:07:58]:
Carmen, you are now tackling three massive challenges. Tell us what they are and what the common denominator between these is.
Carmen Jungo Rhême [00:08:07]:
I would say the three massive challenges at BCC are, first of all, antimicrobial resistance, sustainable food production, and digitalization. At first glance, these three topics might seem like separate challenges, but they are connected by a common factor: the need for smarter bioprocesses.
Antimicrobial resistance pushes us to rethink how we manage microbes—not just in medicine, but also in agriculture and food production. Secondly, sustainable food production demands that we use fewer resources, reduce waste, and maintain safety, all of which benefit from precise biological control. And third, digitalization is the enabler that ties it all together. By collecting and analyzing data from bioprocesses, we can better understand complex systems, predict outcomes, and make faster, more informed decisions. The common thread connecting these three topics is innovation at the intersection of biology and technology to develop smarter bioprocesses.
David Brühlmann [00:09:31]:
So let’s unpack this. How do we make bioprocessing smarter? I love that phrase because that’s the title of the podcast—Smart Biotech Scientist. So that’s excellent. Let’s start with antimicrobial resistance, because I think many of the listeners are not familiar with the challenges. And actually, how does a bioprocess look like to fight these “superbugs”? How does that work?
Carmen Jungo Rhême [00:09:58]:
First of all, it’s important to mention that the emergence and spread of drug-resistant pathogens challenges our ability to treat common infections with existing antimicrobials such as antibiotics. The World Health Organization lists antimicrobial resistance as one of the top challenges for humanity in the next decade.
Currently, several approaches are being explored by the scientific community. For example, the development of new vaccines, monoclonal antibodies, phage therapy, and also the use of recombinant proteins like endolysins to fight difficult-to-treat bacteria.
At the Biofactory Competence Center, we are working in collaboration with CHUV, the University Hospital in Lausanne, in the field of phage therapy. More precisely, we are collaborating with Dr. Grégory Rech from CHUV, who has been working in this area for more than 20 years, and with Dr. Jean-François Brunet from the Centre de Production Cellulaire in Épalinges, also part of CHUV.
They have the first GMP manufacturing line in Switzerland for the production and purification of phages, and they have already started to test it on patients. We are working in collaboration with CHUV, have transferred their process to BCC, and are now performing a full characterization using a Quality by Design approach. This is very important when we talk about smarter bioprocesses—it’s critical to have a complete understanding of the process. Of course, you know all the process steps, but it’s very important to list all the process variables, including process parameters and material attributes, such as raw materials, chemicals, and filters.
We conducted a full risk assessment on each process variable to categorize them as critical or non-critical—for example, regarding product quality or yield. After this assessment, we are now characterizing the key and critical process parameters, collecting data to achieve full process characterization. Of course, this is already standard practice in industry for recombinant protein production, and we are now applying it to a phage production process.
Maybe I can also say a few words about bacteriophages for people who are not familiar. Bacteriophages are viruses that specifically infect and kill bacteria. For each bacterium, there is a specific bacteriophage in nature. They exist naturally all over the planet—they can be found in water, soil, and other environments—and were actually used to treat bacterial infections at the beginning of the 20th century. They were discovered in 1917, while antibiotics were discovered in 1928.
However, their use declined in favor of antibiotics after World War II, because antibiotics were easier to use. Some countries, like Georgia, Poland, and others in the former Soviet Union, continued to use phages because they didn’t always have access to antibiotics. In the last two decades, there has been renewed interest in phage therapy in Europe, the US, and other countries.
We are very proud to develop an innovative process and contribute to its characterization in collaboration with CHUV. Recently, we also started addressing phage formulation through lyophilization, because currently most formulations are stored in liquid form. Lyophilized formulations offer advantages for stability and storage.
David Brühlmann [00:14:15]:
That’s excellent. You’re making a big difference—solving a major problem for humanity. Looking at the production process itself, how does it differ from more established processes, such as mammalian cell culture or E. coli fermentation? Is it similar or very different?
Carmen Jungo Rhême [00:14:35]:
It’s actually very similar. In a process for recombinant protein expression, you have an upstream phase for expression, followed by purification and final formulation. The production and purification of bacteriophages is very similar. The same technologies are used: first, you grow the host bacteria, then add the corresponding phage to amplify it. After harvest, you have a clarification step, followed by purification steps, which are very similar to recombinant protein purification. So the expertise and technologies are very similar.
David Brühlmann [00:15:28]:
And now moving on to your second area, sustainable food production, which has some similarities but also differences. Tell us a bit about what you’re doing there, and how it ties back to digital transformation.
Carmen Jungo Rhême [00:15:42]:
Yes, as you said, we are also working on sustainable food production in the food sector. For example, we work on the valorization of whey permeate by cultivating microalgae on a whey-permeate-based medium. It’s important to mention that there is a lot of whey permeate in Switzerland, thanks to the cheese industry.
We also have experience producing recombinant proteins through precision fermentation using Pichia pastoris. Returning to microalgae, there is huge potential in cultivating microalgae for the sustainable production of proteins and lipids for the food industry. We can grow microalgae to produce specific proteins or lipids, then extract and purify them. I think we are only at the beginning of a major change in the food industry. More and more, food waste will be transformed into high-value nutrients using microalgae, bacteria, yeasts, or even fungi.
David Brühlmann [00:16:59]:
That’s excellent. Now, in academia, I imagine you have a bit more freedom than we would in the corporate world or even in the startup world. Well, in startups, you have freedom, but sometimes you don’t have the resources to fully explore. So what myth or challenge would you like to tackle in your current role?
Carmen Jungo Rhême [00:17:20]:
In bioprocessing, we have more freedom than in industry, so we can be more creative and sometimes explore ideas that we don’t know will work. I think that’s the main difference. We also have projects with our students where there isn’t necessarily a client behind them. When students work on a project, we have complete freedom, and sometimes we take the time to assess more possibilities and just explore.
I think that’s the main difference with startups or industry, where you have to be fast and results are expected in a short time. In academia, with bachelor or master projects that aren’t linked to an industry client, we have the freedom to test new technologies. Sometimes companies also come to us needing data to test prototype equipment, and this is something we can do more freely than in industry.
David Brühlmann [00:18:28]:
And that concludes part one with Carmen Jungo Rhême—from her industry journey to tackling antimicrobial resistance and sustainable food production. In part two, we’ll dive into the Biofactory Competence Center’s game-changing approach to process development and training.
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.
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About Carmen Jungo Rhême
Carmen Jungo Rhême is full professor at the Haute Ecole d’Ingénierie et d’Architecture de Fribourg (HEIA-FR) and Director of the Biofactory Competence Center (BCC). She has extensive experience (17 years) in the pharmaceutical industry with a proven track record in several biopharmaceutical companies manufacturing therapeutic recombinant proteins (Lonza, Merck Serono, UCB Farchim and CSL Behring).
She specialized in bioprocess development, both in cell culture and in purification of proteins, scale-up, and technology transfer of marked products. Since her start at HEIA-FR in November 2023, C. Jungo Rhême has initiated several research projects in the field of antimicrobial resistance, one of them in the field of antimicrobial resistance, sustainable food production, and digitalization of bioprocesses.
Connect with Carmen Jungo Rhême 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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