Smart Biotech Scientist | The CMC and Bioprocessing Podcast for Process Development and Manufacturing Leaders

Episodes

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  300: Where Bioprocess Models Deliver and Where They Overpromise: Choosing Between Hybrid, Mechanistic, and Machine Learning with Moritz von Stosch - Part 2 29.10.2026 22m

  Is your process model gathering dust while real-world decisions march on without it? Many technically strong digital tools—no matter how powerful—end up sidelined in bioprocess development. Why is that, and what does it actually take for digital modeling to earn its place at the lab bench? In this episode, David Brühlmann sits down with Moritz von Stosch of HINA Bioventures, a scientist-turned-investor who’s navigated both the technology provider and pharma end-user sides. Moritz von Stosch b...
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  299: Where Bioprocess Models Deliver and Where They Overpromise: Choosing Between Hybrid, Mechanistic, and Machine Learning with Moritz von Stosch - Part 1 27.10.2026 21m

  Are you frustrated with reinventing the wheel every time a new molecule enters bioprocess development? Is there a better way to harness data and modeling to accelerate breakthroughs in biotech? The bioprocessing industry is constantly searching for ways to streamline development, reduce costs, and speed new therapies to market—yet leveraging existing knowledge remains a significant challenge. In this episode, David Brühlmann welcomes Moritz von Stosch, partner at HINA Bioventures and a pionee...
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  298: 10,000 Structures Are Not Enough: The Data Gap Limiting De Novo Antibody Design with David Younger - Part 2 22.10.2026 16m

  The entire public record of antibody affinity data comes to about half a million measurements, and by David Younger's estimate, upwards of 75% of it is AlphaSeq data from his own company's publications. His conclusion is that no single company can close the gap alone. So he is asking pharma and AI labs to pay for an experiment and share every result with the other members. In Part 2 of this two-part conversation, David Brühlmann talks with Younger, founding CEO of A-Alpha Bio, whose AlphaSeq ...
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  297: 10,000 Structures Are Not Enough: The Data Gap Limiting De Novo Antibody Design with David Younger - Part 1 20.10.2026 28m

  The Protein Data Bank holds about 10,000 antibody-antigen structures and grows by roughly 1,000 a year. David Younger's scaling work suggests that generalizable de novo antibody design needs hundreds of thousands to millions. At that pace, even 200,000 structures is nearly two centuries away. In this episode, David Brühlmann hosts David Younger, founding CEO of A-Alpha Bio and the mind behind the AlphaSeq platform. Trained at the intersection of synthetic biology and computational protein eng...
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  296: Neither Small Molecule nor Biologic: The Cyclodextrin Dimer CMC Challenge with Matthew O'Connor - Part 2 15.10.2026 20m

  Cardiovascular disease has long been managed by slowing its relentless progression. But Matthew O'Connor, CEO of Scientific Affairs at Cyclarity Therapeutics, is betting on an outright paradigm shift: treating atherosclerotic plaque with therapies designed to actively reverse disease, not simply manage symptoms or risk. In this episode, David Brühlmann explores the strategy, regulatory journey, and manufacturing realities behind Cyclarity's unconventional cyclodextrin-based approach—a molecul...
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  295: Neither Small Molecule nor Biologic: The Cyclodextrin Dimer CMC Challenge with Matthew O'Connor - Part 1 13.10.2026 25m

  Why does CMC development still expect every drug to be one molecule with one peak, when new therapeutics don't always fit neatly into existing regulatory or chemical categories? Matthew O'Connor, CEO of Scientific Affairs at Cyclarity Therapeutics, is developing a drug that sits between a small molecule and a biologic. On the Smart Biotech Scientist Podcast, Matthew shared how his team engineered a cyclodextrin dimer that binds and removes 7-ketocholesterol, an oxidized form of cholesterol th...
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  294: Is CFD Overkill for Your Scale-Up? Why It Belongs in Every Biotech Scientist's Toolkit with Christian Witz - Part 2 08.10.2026 22m

  Scale-up doesn't fail because the science was wrong. It fails because a cell's environment in a shake flask has little in common with its environment in a bioreactor. Christian Witz has spent years building the tools to close that gap: simulating exactly what a cell experiences as it moves from bench to plant, before a single liter is wasted finding out the hard way. Continuing from Part 1, David Brühlmann and Christian Witz, CEO and founder of SimVantage, go deeper into how CFD moves from th...
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  293: Is CFD Overkill for Your Scale-Up? Why It Belongs in Every Biotech Scientist's Toolkit with Christian Witz - Part 1 06.10.2026 22m

  You've perfected your process at the bench. Now comes the part that keeps CMC scientists up at night: will it still work at 2,000L? Right now, most teams find out the hard way, through failed runs, wasted batches, and months of delay to patients waiting on a therapy. Christian Witz believes there's a better way: use computational fluid dynamics to see how your cells will actually behave at full scale before you ever run the process, and stop treating scale-up as a guessing game. On this episo...
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  292: The Fool's Game That Became Standard Practice: Perfusion, the ATF, and What Changed with John Bonham-Carter - Part 2 01.10.2026 22m

  Biotech founders often pour everything into building the “perfect” product only to realize their real customers have walked out the door. Chasing perfection can burn money and stall even the most promising CMC innovations. In this episode, David Brühlmann continues his conversation with biotech entrepreneur and investor John Bonham-Carter. John shares his insights on the realities of building and scaling successful biotools companies, from the challenges of fundraising and the importance of a...
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  291: The Fool's Game That Became Standard Practice: Perfusion, the ATF, and What Changed with John Bonham-Carter - Part 1 29.09.2026 30m

  Biotech loves talk of disruptive technology, but few have repeatedly shifted the industry's direction. This episode of the Smart Biotech Scientist Podcast focuses on an idea once dismissed as a fool's game: process intensification through perfusion—now the backbone of leading biomanufacturing platforms. Meet John Bonham-Carter, a serial entrepreneur whose fingerprints are on some of biotech's most transformative tools. From putting the once-ignored ATF system and perfusion on the global stage...
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  290: Batch-to-Batch Variability Is a Design Failure, Not the Norm with Sandra Núñez - Part 2 24.09.2026 20m

  What if building a world-class biotech company didn’t require owning a single piece of manufacturing equipment or even a lab of your own? Most startups obsess over bricks, mortar, and stainless steel. Not Sandra Núñez. She’s challenging the status quo as CEO of Amela Biosciences by running a “virtual plant” model: zero in-house production, everything outsourced, and agility baked into every decision. It’s a bold experiment in redefining what a biotech company can look like. One that’s already...
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  289: Batch-to-Batch Variability Is a Design Failure, Not the Norm with Sandra Núñez - Part 1 22.09.2026 19m

  Batch-to-batch variability isn’t just a minor annoyance in bioprocess development; it’s often a systemic design flaw hiding in plain sight. That’s the challenge Sandra Núñez, CEO of Amela Biosciences, set out to eliminate. Drawing on 15 years across Lonza, Medinova, Baxalta, and Biogen, she’s engineered a new generation of animal-free, recombinant protein matrices that promise researchers experimental consistency on demand. Topics discussed: The widespread issue of batch-to-batch variability ...
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  288: Why the Cell Line Is the CMC Decision You Don't Get to Undo with Sigma Mostafa - Part 2 17.09.2026 21m

  Manufacturability challenges in biotech are becoming more complex as therapies become more potent, formats diversify, and timelines compress across the industry. On this episode, David Brühlmann sits down with Sigma Mostafa, Chief Scientific and Technology Officer at KBI Biopharma. Sigma brings deep expertise in early-stage CMC decision-making and has guided countless programs—from upstart startups to established pipelines—through the traps and trade-offs of process development. Her ground-fl...
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  287: Why the Cell Line Is the CMC Decision You Don't Get to Undo with Sigma Mostafa - Part 1 15.09.2026 18m

  A breakthrough in drug discovery can be derailed in an instant if manufacturability is left as an afterthought. Too many biotech programs hit bottlenecks at scale-up because key decisions in cell line and process development get kicked down the road. On the Smart Biotech Scientist Podcast, David Brühlmann spoke with Sigma Mostafa, Chief Scientific and Technology Officer at KBI Biopharma. She’s spent 25+ years converting early-stage discoveries into commercial biomanufacturing success and she’...
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  286: Why Your Dormant Omics Data Is Worth More Than the Data You'll Generate Next with Nathan Lewis - Part 2 10.09.2026 17m

  What does it take to crack the code of protein production and why do some proteins stubbornly refuse to cooperate, despite the best efforts of scientists and engineers? Biotech’s ambitions are often limited not by vision, but by the real-world bottlenecks of host cell lines and the unpredictability of post-translational modifications. Nathan Lewis, GRA Eminent Scholar at the Center for Molecular Medicine, Complex Carbohydrate Research Center, and Department of Biochemistry and Molecular Biolo...
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  285: Why Your Dormant Omics Data Is Worth More Than the Data You'll Generate Next with Nathan Lewis - Part 1 08.09.2026 30m

  Dormant omics data are a goldmine for CMC innovation waiting to be unlocked. But legacy structures, poor annotation, and spreadsheet chaos hold most biotech teams back from the real breakthroughs. Nathan Lewis, GRA Eminent Scholar at the Center for Molecular Medicine, Complex Carbohydrate Research Center, and Department of Biochemistry and Molecular Biology at the University of Georgia, has a clear message: actionable data is now within reach thanks to hybrid modeling, advanced study design, ...
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  284: Detecting 1 in 100,000 Cells: DNA Barcoding for Smarter Clone Selection with Kent Rapp - Part 2 03.09.2026 20m

  “Does DNA barcoding actually work?” It's the first question Kent Rapp hears from prospective customers when he pitches Biolinco's DNA barcoding platform. By his own admission, the technology can sound too good to be true. In Part 2 of this conversation, Kent rejoins the Smart Biotech Scientist Podcast to address that skepticism head-on, unpack how subclone variability and bispecific antibody purity concerns shape customer trust, and share what it actually took to move Biolinco from a Johns Ho...
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  283: Detecting 1 in 100,000 Cells: DNA Barcoding for Smarter Clone Selection with Kent Rapp - Part 1 01.09.2026 21m

  What if the bottleneck in cell line development isn’t how many clones you screen, but how you track them? Cloning workflows have long relied on brute force: screen more cells, automate harder, and hope that small-scale performance predicts manufacturability. But too often, the “perfect” clone in a 96-well plate turns into a dud when it reaches the bioreactor. That disconnect costs time, money, and promising therapies. This week, host David Brühlmann welcomes Kent Rapp, Co-founder and CEO of B...
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  282: When Your Delivery Vehicle Contains a Membrane Protein: CMC Decisions With No Regulatory Precedent with Jitendra Kumar - Part 2 27.08.2026 19m

  Your active ingredient is the nucleic acid. So why does a proteolipid vehicle filing include viral clearance studies, stability data and full characterisation of a membrane protein that is not the drug? Because that protein sits on the particle surface, and a component nobody has filed before is the agency's problem regardless of what you call it. Proteolipid vehicles (PLVs), the platform Jitendra Kumar works on as Lead Scientist for Chemistry and Process Development at Entos Pharmaceuticals,...
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  281: When Your Delivery Vehicle Contains a Membrane Protein: CMC Decisions With No Regulatory Precedent with Jitendra Kumar - Part 1 25.08.2026 20m

  Gene therapy only works if the cargo reaches the right cells intact. Adeno-associated viruses (AAV) and lipid nanoparticles have carried the field this far, but both share a constraint: the particle is taken up into an endosome, and the payload has to escape that compartment before it is degraded. Endosomal escape is where a large share of the dose is lost, and it is why delivery, not the genetic construct, is usually the thing that limits the therapy. Lipid nanoparticles carry a second const...