Smart Biotech Scientist | Master Bioprocess CMC Development, Biologics Manufacturing & Scale-up, Cell Culture Innovation

David Brühlmann - CMC Development Leader, Biotech C-level Advisor, Business Strategist
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  • LIFE SCIENCES
  • UPDATED WEEKLY

The Go-to Podcast for Biotech Scientists Who Want to Master Biopharma CMC Development and Biomanufacturing. **TOP 10 LIFE SCIENCES PODCAST** Are you ready to simplify bioprocess development and scale with confidence to reduce time to market? Are you feeling overwhelmed by the complexity and guesswork of biologics development and biomanufacturing? Do you wish you had more time to enjoy the beauty of science, without worrying about failing your cell culture process development and commercialization? There's a way to simplify and streamline so you can remove complexity, skip trials and errors, deliver your groundbreaking therapy to clinics and market without delay, and still enjoy every single step. I'm David Brühlmann, a biotech entrepreneur and strategic advisor who partners with C-level biopharma leaders to tackle one of our industry's biggest challenges: reducing manufacturing costs to make lifesaving therapies accessible to more patients worldwide. Through engaging conversations with industry pioneers and practical insights from the trenches, this podcast tackles the critical challenges in bioprocess CMC development and manufacturing of recombinant proteins and cell and gene therapy products. We cut through the complexity so you can: Master bioprocess development with confidence and clarity Excel at scale-up and manufacturing of biologics Transform your innovative therapy and manufacturing technology into market-ready solutions faster Optimize manufacturing costs without compromising quality Make data-driven decisions that reduce the risk of failure I can’t wait to help you do biotech the smart way. Grab a cup of coffee and your favorite notebook and pen. Now is the time to take your bioprocessing game to the next level. Ready to transform your biomanufacturing journey? Let's dive in! Next Steps: Book a free call to reduce biomanufacturing costs and make lifesaving therapies more accessible: https://bruehlmann-consulting.com/call 🧬 Ready to accelerate your IND timeline? Get the proven CMC Dashboard that's guided successful mAb programs from chaos to submission: https://stan.store/SmartBiotech/p/cmc-dashboard-for-biotech-founders Accelerate biologics development with expert guidance: https://bruehlmann-consulting.com For sponsorship opportunities, contact us at hello@bruehlmann-consulting.com Visit the Website: https://smartbiotechscientist.com Email us: hello@bruehlmann-consulting.com

  1. 1D AGO

    221: From 2D Cultures to Advanced 3D Cell Models for Preclinical Research with Catarina Brito - Part 1

    What if the failure rate in clinical trials isn't about picking the wrong drug candidates—but about testing them in the wrong models? When you move cells from a 2D culture plate into a bioreactor, you're not simply scaling volume. You're fundamentally changing the biological context. Cell density shifts. Mass transfer dynamics evolve. Mechanical cues emerge. The cells sense these changes and respond—often in ways that derail strategies built on oversimplified assumptions. Most preclinical research still relies on flat plastic surfaces and animal models that miss critical aspects of human biology. The result? Therapeutics fail late in development because the models couldn't predict how human tissues would actually respond. In this episode, David Brühlmann speaks with Catarina Brito, Principal Investigator at ITQB NOVA and Head of the Advanced Cell Models Laboratory at iBET and ITQB NOVA in Portugal. Catarina's career-defining insight came early: studying glycan-protein interactions in murine versus human cells revealed that species differences weren't just nuances—they were fundamental gaps that could mislead entire research programs. Catarina and her team have developed neural, liver, and tumor models that capture the multicellular complexity and microenvironmental cues that 2D cultures cannot replicate. Her work creates preclinical models sophisticated enough to predict human responses while remaining scalable for drug development workflows. Highlights of the episode: Limitations of traditional 2D cell cultures and animal models in capturing realistic tissue behavior and therapeutic responses (06:27)Catarina Brito's personal scientific journey: from discovering model limitations to pioneering 3D culture systems in neural and liver tissues (04:19)How advanced 3D models recreate cell-to-cell interactions, tissue-specific microenvironments, diffusion gradients, and multicellular complexity (10:35)Regulatory movements toward reducing animal models, and the challenge of validating advanced alternatives for systemic biology studies (09:10)Key differences in designing bioreactors for various cell types, with practical examples from liver and neural models (15:16)The impact of scalable, robust 3D models on accelerating drug development and improving selection of candidate therapies (17:22)Key Takeaway: Bioprocess development starts when you choose the model that validates your therapeutic approach. If that model can't capture the biology that matters, every downstream optimization is built on a flawed foundation. In Part 2, Catarina reveals how 3D tumor microenvironments expose drug resistance mechanisms invisible in 2D cultures, and her vision for AI-powered digital twins enabling personalized medicine. Subscribe & Review: If this conversation changed how you think about preclinical model selection, leave a review on Apple Podcasts. Your reviews help other biotech scientists discover these insights. For more CMC development insights, visit smartbiotechscientist.com. Connect with Catarina Brito: LinkedIn: www.linkedin.com/in/catarina-brito-ibet Advanced Cell Models Lab – iBET: www.ibet.pt/laboratories/advanced-cell-models-lab Next step: Need fast CMC guidance? → Get rapid CMC decision support here Support the show

    20 min

  2. 6D AGO

    220: From 10,000 Structures to 1.8 Billion Interactions: Breaking the Data Bottleneck to Engineer Efficacious Therapeutics with Troy Lionberger - Part 2

    The biotech industry stands on the verge of a radical transformation thanks to artificial intelligence (AI) and machine learning (ML). But even the most sophisticated algorithms are only as smart as the data feeding them. David Brühlmann sits down with Troy Lionberger, Chief Business Officer at A-Alpha Bio, whose team has quietly shattered the data ceiling by measuring and curating more than 1.8 billion protein interactions. Troy Lionberger brings an insider’s perspective from the frontlines of machine learning-powered drug discovery. From partnering with leading biotechs to redesigning classic antibodies for previously “impossible” targets, Troy’s work pushes the edges of what’s tractable in biologic therapeutics. What you'll hear in this episode: Limitations of public data sources like the Protein Data Bank and their impact on current protein engineering approaches (03:11)Why combining energetic (ΔG) and structural data matters for building predictive protein engineering models (05:43)A-Alpha Bio’s approach to generating 1.8 billion protein interaction measurements for machine learning—what this enables today and what’s possible next (06:30)Examples of how A-Alpha Bio’s platform solves challenging therapeutic problems, such as optimizing molecules for 800+ HIV variants and engineering dual-specific antibodies (07:36)The ongoing debate: What capabilities should biotech companies keep in-house, and what works best outsourced to service providers? (09:59)The potential of synthetic epitopes as vital tools for training models beyond the Protein Data Bank—introducing the Synthetic Epitope Atlas (12:09)Key takeaways for scientists: the importance of diligence amidst rapidly evolving AI claims, and advice for accelerating R&D with the right data (14:57)Wondering how to move protein therapeutics from “interesting” to “impactful” without waiting for years of crystal structures? Listen in to learn how you can harness next-gen machine learning tools and custom datasets for your development projects. Connect with Troy Lionberger: LinkedIn: www.linkedin.com/in/troylionberger A-Alpha Bio website: www.aalphabio.com Next step: Need fast CMC guidance? → Get rapid CMC decision support here Support the show

    18 min

  3. JAN 13

    219: From 10,000 Structures to 1.8 Billion Interactions: Breaking the Data Bottleneck to Engineer Efficacious Therapeutics with Troy Lionberger - Part 1

    Antibody therapeutics have transformed modern medicine, but for many scientists, developing new candidates still feels like searching for a needle in a haystack—a slow, expensive, and unpredictable process. Structural biology and high-throughput data generation are now collapsing that haystack, offering unprecedented visibility into the molecular handshake that drives life: protein-protein interactions. In this episode, David Brühlmann sits down with Troy Lionberger, Chief Business Officer at A-Alpha Bio, for an in-depth discussion on protein-protein interactions and how advances in data generation and machine learning are transforming antibody discovery and drug development. Troy Lionberger shares his journey into biotechnology, challenges long-held beliefs about antibody development, and explains how Alphabio's high-throughput affinity measurements are shortening timelines and improving outcomes for therapeutic development. In this episode, you’ll learn about: The historical and current challenges in characterizing these interactions at scale (06:22)How new technologies—especially high-throughput platforms—are changing the needle-in-the-haystack approach (08:40)A comparison of traditional in vivo and in vitro antibody discovery methods, along with their strengths and limitations (09:06)The evolving role of AI and machine learning in antibody discovery and lead optimization (12:11)Real-world examples of how A-Alpha Bio’s approach is compressing years of work into months without sacrificing quality (13:58)The science behind A-Alpha Bio’s AlphaSeq technology and how it leverages yeast display and genomics for large-scale affinity measurements (20:43)The practical affinity range the technology can measure, covering most therapeutic applications (23:25)Whether you’re a scientist navigating CMC or a biotech professional curious about next-generation workflows, this episode offers practical insights into both traditional and emerging methodologies in the field. Connect with Troy Lionberger: LinkedIn: www.linkedin.com/in/troylionberger A-Alpha Bio website: www.aalphabio.com Next step: Need fast CMC guidance? → Get rapid CMC decision support here One bad CDMO decision can cost you two years and your Series A. If you're navigating tech transfer, CDMO selection, or IND prep, let's talk before it gets expensive. Two slots open this month. Support the show

    27 min

  4. JAN 8

    218: Silkworm Biomanufacturing: From Ancient Silk Production to Phase I Vaccine Trials with Masafumi Osawa - Part 2

    For generations, silkworm pupae were discarded as waste from silk production. Now, KAICO is proving these organisms can function as highly efficient protein factories—producing complex vaccine antigens at yields and costs that challenge conventional bioreactor-based manufacturing. With a PCV2 oral vaccine already registered in Vietnam and a human norovirus vaccine preparing for Phase I clinical trials, the silkworm platform is moving from proof-of-concept to commercial reality. In Part 2, Masafumi Osawa, Business Development Lead at KAICO, walks us through the company's product pipeline, the regulatory landscape for this unprecedented platform, and why silkworm-based manufacturing could reshape global vaccine accessibility. From farm-scale validation to regulatory dialogue with Japan's PMDA, this episode bridges platform science with product development. Stops along our Silk Road to biomanufacturing KAICO’s approach to expressing complex proteins, including oral and injectable vaccines for animals and clinical-stage human health products (00:40)Immune-enhancing feed additive for pigs against PCV2 (registered in Vietnam), companion animal products, and human norovirus vaccine entering Phase 1 trials (02:50)Advantages of silkworm-produced antigens for both injectable and oral vaccines, and comparison to plant-based systems (04:57)How silkworm production enables rapid scale-out and high-yield protein expression for global accessibility (05:34)Speed of vaccine development with the silkworm platform—example with SARS-CoV-2 recombinant protein produced in three months (08:08)Key regulatory differences between animal and human vaccine development, including country-specific classification and global harmonization efforts (09:14)Sustainability and distributed manufacturing potential of silkworm-based systems (11:10)Milestones toward the first human biologic produced in silkworms, with phase 1 trials starting soon (12:27)Protein yield per silkworm pupae—scalability advantages compared to conventional bioreactor approaches (14:04)Masafumi Osawa’s thoughts on the future of silkworm-based biologics: from democratized therapies to personalized medicines (15:15)Want to know if silkworms can solve your tough protein expression problems? Tune in now to learn how KAICO’s biotech is set to redefine what’s possible for vaccine development, and how their distributed, cost-effective approach could open doors across sectors. Connect with Masafumi Osawa,: LinkedIn: www.linkedin.com/in/masa-osawa KAICO Ltd.: www.kaicoltd.jp/en Next step: Need fast CMC guidance? → Get rapid CMC decision support here Support the show

    18 min

  5. JAN 6

    217: Silkworm Biomanufacturing: From Ancient Silk Production to Phase I Vaccine Trials with Masafumi Osawa - Part 1

    For over 4,000 years, silkworms have connected civilizations through ancient trade routes. Now, KAICO Ltd., a Japanese biotech spin-off from Kyushu University, is transforming these creatures into living bioreactors capable of producing complex recombinant proteins and vaccine antigens—without the bioreactors, expensive media, or massive water consumption of conventional platforms. Masafumi Osawa, Business Development Lead at KAICO, brings an unconventional path to biotech. Trained in cultural anthropology with fieldwork experience in Indonesia, he witnessed firsthand the healthcare disparities that drive his current mission. After years in pharmaceutical business development at Towa Pharmaceutical, he joined KAICO to help scale a technology he believes could reshape global vaccine accessibility. His cross-cultural expertise now proves invaluable as KAICO expands internationally, with active partnerships in Vietnam and Thailand and growing interest from other regions. Episode highlights: Masafumi’s transition from anthropology to biotech, and how cross-cultural expertise benefits global health collaborations. (04:15)The founding story of KAICO, spun out from Kyushu University and focused on recombinant proteins and vaccine antigen production (08:45)Step-by-step overview of the silkworm baculovirus expression system, including pupae handling and bioprocessing basics. (10:28)Practical differences between silkworms, E. coli, mammalian, and insect cell culture platforms—exploring advantages and drawbacks. (13:10)Strategies KAICO uses to control silkworm variability, including SPF grade sourcing, diet, environment, and documentation for pharmaceutical acceptance. (15:08)Production scalability: a single pupa can match 100–1000 ml of insect cell culture, with major implications for cost and environmental footprint. (16:42)Downstream harvesting and purification—how KAICO extracts and processes proteins from silkworm pupae, keeping methods largely familiar to traditional systems. (19:31)Regulatory and GMP challenges of using live organisms, and KAICO’s approach to satisfying authorities and ensuring product consistency. (21:43)Whether you’re curious about alternative biomanufacturing methods or want a transparent look at silkworm-based protein expression from research to the clinic, this episode delivers practical insights and thoughtful discussion. Connect with Masafumi Osawa: LinkedIn: www.linkedin.com/in/masa-osawa KAICO Ltd.: www.kaicoltd.jp/en Next step: Need fast CMC guidance? → Get rapid CMC decision support here One bad CDMO decision can cost you two years and your Series A. If you're navigating tech transfer, CDMO selection, or IND prep, let's talk before it gets expensive. Two slots open this month. Support the show

    25 min

  6. 12/18/2025

    216: From Data Silos to Autonomous Biomanufacturing: Digital Twins and AI-Driven Scale-Up with Ilya Burkov - Part 2

    Biomanufacturing has always dealt with the challenge of turning vast, complex datasets and intricate production steps into life-changing therapies. But when batch records multiply and process deviations loom, how do biotech teams make sense of it all? In this episode, we move beyond theory to the nuts and bolts of how AI - when thoughtfully deployed - can turn bioprocessing chaos into actionable intelligence, paving the way for the factory of the future. Our guest, Ilya Burkov, Global Head of Healthcare and Life Sciences Growth at Nebius AI, doesn’t just talk about data wrangling and algorithms—he’s spent years building tools and strategies to help scientists organize, contextualize, and leverage real-world datasets. Having worked across tech innovation and pharmaceuticals, Ilya Burkov bridges cutting-edge computation with the practical realities of CMC development and manufacturing, making him a trusted voice on how bioprocessing is rapidly changing. Highlights from the episode: Advice for biotech scientists on learning from innovations in other industries (00:02:21)Tackling the complexities of organizing huge and often unstructured datasets in bioprocessing (03:08)Techniques and tools to structure, label, and prepare data for AI—including Nebius’s in-house tool, Tracto AI (06:24)Strategies for startups and small teams—how to begin implementing AI and what areas of bioprocessing to focus on first (10:12)The vision for the “factory of the future”: AI-driven, interconnected, and self-learning manufacturing environments (08:11)Navigating the decision between on-premise and cloud computing for scalable, cost-effective AI workloads (12:32)The importance of partnership between scientists and AI, emphasizing collaboration and data-driven decisions (00:15:47)Wondering how to kick off your own AI-enabled bioprocessing project, or what to insource versus outsource as you scale? This episode gives you a grounded starting point—minus the buzzwords and empty promises. Connect with Ilya Burkov: LinkedIn: www.linkedin.com/in/ilyaburkov Contact email: ilya.burkov@nebius.com Nebius: www.nebius.com If this topic grabbed you, you'll love these related episodes focusing on advanced modeling, continuous manufacturing, and Digital Twins Episodes 213 - 214: From Developability to Formulation: How In Silico Methods Predict Stability Issues Before the Lab with Giuseppe LicariEpisodes 85 - 86: Bioprocess 4.0: Integrated Continuous Biomanufacturing with Massimo MorbidelliEpisodes 05 - 06: Hybrid Modeling: The Key to Smarter Bioprocessing with Michael SokolovEpisode 153 - 154: The Future of Bioprocessing: Industry 4.0, Digital Twins, and Continuous Manufacturing Strategies with Tiago MatosEpisodes 173 - 174: Mastering Hybrid Model Digital Twins: From Lab Scale to Commercial Bioprocessing with Krist GernaeyNext step: Need fast CMC guidance? → Get rapid CMC decision support here Support the show

    19 min

  7. 12/16/2025

    215: From Data Silos to Autonomous Biomanufacturing: Digital Twins and AI-Driven Scale-Up with Ilya Burkov - Part 1

    Across biotech labs, researchers swim in oceans of process data: sensor streams, run records, engineering logs, and still, crucial decisions get stuck in spreadsheets or scribbled into fading notebooks. The challenge isn’t having enough information, it's knowing which actions actually move the needle in cell culture productivity, process stability, and faster timelines. This episode, David Brühlmann brings on Ilya Burkov, Global Head of Healthcare and Life Sciences Growth at Nebius AI. With a career spanning NHS medicine, regenerative research, and cloud infrastructure, Ilya Burkov has lived the leap from microscope to server room. He’s seen firsthand how digital twins, autonomous experimentation, and cloud-first strategies are shifting the way biologics are developed and scaled. Topics discussed: Shifting from experimental-based to computational bioprocess development, and the evolving role of human expertise vs. AI (02:48)Ilya Burkov's journey from medicine and orthopedics to AI and cloud infrastructure (04:15)Solving data silos and making real-time decisions with digital twins and automated analytics (06:36)The impact of AI-driven lab automation and robotics on drug discovery timelines (08:51)Using AI to accelerate cell line selection, cloning, and protein sequence optimization (10:12)Why wet lab experimentation is still essential, and how predictive modelling can reduce failure rates (11:15)Reducing costs and accelerating development by leveraging AI in process screening and optimization (12:32)Strategies for smaller companies to effectively store and manage bioprocess data, including practical advice on cloud adoption and security (14:30)Application of AI and digital twins in scale-up processes, and connecting diverse data types like CFD simulations and process data (17:18)The ongoing need for human expertise in interpreting and qualifying data, even as machine learning advances (19:09)Wondering how to stop your own data from gathering dust? This episode unpacks practical strategies for storing and leveraging your experimental records - whether you’re in a major pharma or a small startup with limited tech resources. Connect with Ilya Burkov: LinkedIn: www.linkedin.com/in/ilyaburkov Contact email: ilya.burkov@nebius.com Nebius: www.nebius.com If this topic grabbed you, you'll love these related episodes focusing on advanced modeling, continuous manufacturing, and Digital Twins Episodes 213 - 214: From Developability to Formulation: How In Silico Methods Predict Stability Issues Before the Lab with Giuseppe LicariEpisodes 85 - 86: Bioprocess 4.0: Integrated Continuous Biomanufacturing with Massimo MorbidelliEpisodes 05 - 06: Hybrid Modeling: The Key to Smarter Bioprocessing with Michael SokolovEpisode 153 - 154: The Future of Bioprocessing: Industry 4.0, Digital Twins, and Continuous Manufacturing Strategies with Tiago MatosEpisodes 173 - 174: Mastering Hybrid Model Digital Twins: From Lab Scale to Commercial Bioprocessing with Krist GernaeyNext step: Need fast CMC guidance? → Get rapid CMC decision support here Support the show

    22 min

  8. 12/11/2025

    214: From Developability to Formulation: How In Silico Methods Predict Stability Issues Before the Lab with Giuseppe Licari - Part 2

    Computational methods can predict stability issues before the lab. But how do you actually implement these approaches in your formulation workflow? From excipient selection to long-term stability prediction, in silico tools are transforming how biotech teams develop robust formulations while reducing costly trial-and-error cycles. In Part 2, Giuseppe Licari, Principal Scientist in Computational Structural Biology at Merck KGaA, returns to share practical implementation strategies for integrating computational methods into biologics formulation development. Giuseppe reveals how molecular dynamics simulations guide excipient selection, where current methods hit their limits, and how emerging AI capabilities are expanding what's possible in formulation prediction. Whether you're at a well-resourced pharma company or a lean startup, Giuseppe offers actionable guidance for leveraging computational tools to predict protein behavior, optimize formulations, and accelerate your development timeline. Topics covered: Predicting protein aggregation and excipient interactions before manufacturing (00:45)Using molecular dynamics to understand protein behavior over time and in different environments (03:03)The interplay between computational predictions and experimental stability studies (04:49)The limitations of current in silico methods for predicting long-term stability (05:08)Emerging use of AI and machine learning to predict protein properties and improve developability (06:36)Future possibilities: Generative AI for protein design and formulation prediction (08:06)Advice for small companies: leveraging software-as-a-service and external partners to access computational tools (09:55)The impact of increasing computational power on the field's evolution (11:12)Most important takeaway: being open and curious about new computational techniques in biotech formulation (12:08)Discover how to bridge computational predictions with experimental validation, navigate the current limitations of in silico stability forecasting, and position your organization to benefit from AI-driven formulation development, regardless of your resource constraints. Connect with Giuseppe Licari to continue the conversation and explore how computational approaches can solve your formulation challenges before you ever step into the lab. Connect with Giuseppe Licari: LinkedIn: www.linkedin.com/in/giuseppe-licari Next step: Need fast CMC guidance? → Get rapid CMC decision support here Support the show

    15 min
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The Go-to Podcast for Biotech Scientists Who Want to Master Biopharma CMC Development and Biomanufacturing. **TOP 10 LIFE SCIENCES PODCAST** Are you ready to simplify bioprocess development and scale with confidence to reduce time to market? Are you feeling overwhelmed by the complexity and guesswork of biologics development and biomanufacturing? Do you wish you had more time to enjoy the beauty of science, without worrying about failing your cell culture process development and commercialization? There's a way to simplify and streamline so you can remove complexity, skip trials and errors, deliver your groundbreaking therapy to clinics and market without delay, and still enjoy every single step. I'm David Brühlmann, a biotech entrepreneur and strategic advisor who partners with C-level biopharma leaders to tackle one of our industry's biggest challenges: reducing manufacturing costs to make lifesaving therapies accessible to more patients worldwide. Through engaging conversations with industry pioneers and practical insights from the trenches, this podcast tackles the critical challenges in bioprocess CMC development and manufacturing of recombinant proteins and cell and gene therapy products. We cut through the complexity so you can: Master bioprocess development with confidence and clarity Excel at scale-up and manufacturing of biologics Transform your innovative therapy and manufacturing technology into market-ready solutions faster Optimize manufacturing costs without compromising quality Make data-driven decisions that reduce the risk of failure I can’t wait to help you do biotech the smart way. Grab a cup of coffee and your favorite notebook and pen. Now is the time to take your bioprocessing game to the next level. Ready to transform your biomanufacturing journey? Let's dive in! Next Steps: Book a free call to reduce biomanufacturing costs and make lifesaving therapies more accessible: https://bruehlmann-consulting.com/call 🧬 Ready to accelerate your IND timeline? Get the proven CMC Dashboard that's guided successful mAb programs from chaos to submission: https://stan.store/SmartBiotech/p/cmc-dashboard-for-biotech-founders Accelerate biologics development with expert guidance: https://bruehlmann-consulting.com For sponsorship opportunities, contact us at hello@bruehlmann-consulting.com Visit the Website: https://smartbiotechscientist.com Email us: hello@bruehlmann-consulting.com

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