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

What if the key to unlocking ADC manufacturing success lies in abandoning the platform mindset entirely?Antibody-drug conjugates represent biotech's most promising weapon against cancer: precision-targeted therapeutics that deliver cytotoxic payloads directly to tumor cells while sparing healthy tissue. But beneath the clinical promise lies a manufacturing reality that's rewriting the rules of bioprocess development, demanding analytical strategies that most CDMOs simply aren't equipped to handle.In this deep-dive episode, David Brühlmann sits down with Amanda Hoertz, Vice President of Analytical and Formulation Sciences at KBI Biopharma, where she oversees 300+ scientists across the mammalian network. Amanda's team has cracked the code on some of the industry's most challenging ADC programs, achieving a remarkable 93% batch success rate by rejecting cookie-cutter approaches in favor of molecule-specific development strategies.What you'll discover:The Platform Fallacy: Why treating ADCs like standard monoclonals is costing companies millions and months of development time, and the bespoke analytical framework that's changing everything.Cytotoxic Payload Management: From free drug analysis to employee safety protocols, Amanda reveals the hidden complexities of handling molecules designed to kill cells, including the specialized facilities and analytical methods required for GMP manufacturing.Charge Heterogeneity Mastery: The analytical method that "keeps Amanda up at night," and the development strategies her team uses to achieve robust separation and qualification across multiple sites and analysts.This episode delivers the technical depth and strategic insights that bioprocess engineers need to navigate ADC development successfully. Whether you're evaluating CDMO partnerships, optimizing analytical methods, or scaling complex conjugates, Amanda's proven strategies will transform your approach to these game-changing therapeutics.Ready to master the analytical complexities that make or break ADC programs?Connect with Amanda Hoertz:LinkedIn: www.linkedin.com/in/amanda-hoertz-3aba605KBI Biopharma: www.kbibiopharma.comKBI Portal: www.standalone.kbi.bioNext step:Book a 20-minute call to help you get started on any questions you may have about bioprocessing analytics: https://bruehlmann-consulting.com/call🧬 Stop second-guessing your CMC strategy. Get an investor-ready CMC roadmap in 2 weeks, before mistakes cost you $2M+ and 18 months of delays. Secure your spot at https://stan.store/SmartBiotech/p/dont-let-cmc-kill-your-funding-roundSupport the show

What if solving tomorrow’s bioprocessing challenges meant questioning the very physics of chromatography and reimagining downstream processing from the ground up?For years, large biomolecules like viral vectors and exosomes have squeezed through the limitations of traditional chromatography, leaving scientists to wrestle with capacity trade-offs and slow mass transfer. But what if a fundamental shift could unlock breakthroughs for gene therapies, vaccines, and advanced biologics?In this thought-provoking episode, host David Brühlmann sits down with Alois Jungbauer, professor emeritus of downstream processing at BOKU University (Vienna) and scientific advisor at BioChromatographix International. Together, they examine the future of chromatography and downstream processing, exploring innovations that tackle the challenges of modern gene therapy, advanced therapeutics, and sustainability in manufacturing.Alois shares his perspective on anticipating industry needs, the importance of mentorship, and why the physical limits for purification of large biomolecules are yet to be reached.Episode Highlights:The difference between solving current problems and anticipating the needs of the next generation in biotech (00:00)The promise and technical details of monolithic chromatography and its application for large modalities like gene therapy vectors and exosomes (03:01)Explanation of “inverted morphology" and AXISFLOW™ in new chromatography materials (03:18)Challenges and opportunities in continuous gene therapy vector production, and why it’s not widespread yet (07:40)The critical role of sustainability in downstream processing, particularly water usage and its impact on the viability and costs of distributed manufacturing (10:30)The relationship between reducing water consumption, manufacturing footprint, and cost of goods (12:16)Advice on scientific career development: listening, reading, understanding future industry needs, finding a mentor, and having persistence (13:50)Broader reflections on the value of science, societal perceptions, and science communication in today’s world (17:34)Alois’s key takeaway: downstream processing for gene therapy has not yet reached its physical limits—there is still significant room for improvement (20:26)If you’re looking for fresh strategies to tackle the bottlenecks of large-molecule purification - and a candid perspective on where the real opportunities and societal responsibilities lie - you won’t want to miss this conversation.Connect with Alois Jungbauer at leading conferences, including Bioprocessing Summit and Bioprocessing International, or find the next integrated continuous biomanufacturing event where he’s co-chairing.Connect with Alois Jungbauer:LinkedIn: www.linkedin.com/in/alois-jungbauer-14984811Website : www.biochromatographix.comNext step:Book a 20-minute call to help you get started on any questions you may have about bioprocessing analytics: https://bruehlmann-consulting.com/callPreparing for your IND? We’re building a CMC Dashboard in Excel to help biotech founders track tasks, timelines, and risks in one place. Join the waitlist for early access at 🧬 Stop second-guessing your CMC strategy. Get an investor-ready CMC roadmap in 2 weeks, before mistakes cost you $2M+ and 18 months of delays. Secure your spot at https://stan.store/SmartBiotech/p/dont-let-cmc-kill-your-funding-roundSupport the show

In this episode, host David Brühlmann is joined by Alois Jungbauer, Professor Emeritus at BOKU University, Vienna, and Scientific Advisor at BioChromatographix International. With over 40 years in bioprocess engineering and more than 400 published papers, Jungbauer offers a unique perspective on how downstream processing and purification technologies have evolved and where they’re headed next.Alois shares his unconventional journey into the world of biotech, starting from humble beginnings on an Austrian farm, and discusses key turning points that have shaped the industry. Together, they explore the latest challenges triggered by high cell culture titers, new therapeutic modalities, and the drive for automation and process integration in manufacturing.In this episode:Why the gap between upstream and downstream processes remains a core bottleneck (03:27)How rigid and convective chromatography materials changed throughput and efficiency (06:56)The shift in purification strategies with skyrocketing titers in cell culture (08:43)Automation and integrated biomanufacturing: their role in making processes more robust and continuous (10:20)Misconceptions around resin costs in full-scale versus clinical-scale manufacturing (12:10)What automation and process monitoring mean for real-time release and factory scheduling (14:05)The resurgence and application of displacement chromatography for gene therapy vectors (15:49)Whether you’re deep into process development or just curious about the next wave in biotech manufacturing, Alois Jungbauer’s insights offer valuable context for the road ahead.Connect with Alois Jungbauer:LinkedIn: www.linkedin.com/in/alois-jungbauer-14984811Website : www.biochromatographix.comNext step:Book a 20-minute call to help you get started on any questions you may have about bioprocessing analytics: https://bruehlmann-consulting.com/callPreparing for your IND? We’re building a CMC Dashboard in Excel to help biotech founders track tasks, timelines, and risks in one place. Join the waitlist for early access at https://scale-your-impact.notion.site/27dd9c6ba679804b80a7ce439d56c91a?pvs=105🧬 Stop second-guessing your CMC strategy. Get an investor-ready CMC roadmap in 2 weeks, before mistakes cost you $2M+ and 18 months of delays. Secure your spot at https://stan.store/SmartBiotech/p/dont-let-cmc-kill-your-funding-roundSupport the show

What if the future of affordable, life-changing cell and gene therapies comes down to one critical yet often overlooked factor: manufacturing efficiency?In advanced therapy medicinal products (ATMPs), groundbreaking science abounds, but the path to the clinic is still strewn with bottlenecks, especially when it comes to cost, complexity, and safety. While the promise is enormous, most therapies remain out of reach for many patients due to high cost of goods and logistical hurdles. What can actually break down these barriers and democratize access?In this episode, David Brühlmann welcomes Lucas Chan, celebrated Fellow of the Royal Society of Biology, advisor to Singapore's Ministry of Health, and a true pioneer in viral vector manufacturing. In Singapore, he founded CellVec Pte Ltd – APAC’s first regulatory accredited Viral Vector specialist CDMO.Lucas's leadership spans founding ventures in emerging markets to championing game-changing innovations in gene transfer, always with an eye toward efficiency, safety, and accessibility. Having returned “back to the bench” in collaboration with the National University of Singapore while launching his consultancy, Lucas brings both visionary perspective and hands-on experience to one of biotech’s toughest challenges.Here are three reasons why you need to listen to this episode:Efficiency is Everything: Lucas dissects how complex processes and outdated manufacturing paradigms are driving up the cost of cell and gene therapies and shares real-world advances, from transitioning viral vector production to stable producer cell lines to the emergence of non-viral gene transfer modalities, that are poised to rewrite the rulebook on scalability and affordability.Leadership Amid Complexity: Learn from Lucas’s top leadership advice drawn from his CSO and CDMO tenure: inspire teams by connecting every task to the larger mission. In a multidisciplinary, high-stakes environment, alignment and motivation aren’t just nice, they’re essential for innovation.Entrepreneurship and Community: Thinking of turning your biotech expertise into a startup? Lucas underscores the value of learning from others’ journeys, collaboration, and the insight that “it takes a village” when translating advanced therapies from bench to bedside, especially in emerging markets with unique affordability challenges.Want to transform your approach to cell and gene therapy manufacturing or just need inspiration to push your biotech project to the next level?Tune into this episode for practical insights, candid leadership lessons, and a renewed sense of what’s possible when we challenge the status quo together.Connect with Lucas Chan:LinkedIn: www.linkedin.com/in/lucaschangtNext step:Book a 20-minute call to help you get started on any questions you may have about bioprocessing analytics: https://bruehlmann-consulting.com/callPreparing for your IND? We’re building a CMC Dashboard in Excel to help biotech founders track tasks, timelines, and risks in one place. Join the waitlist for early access at https://scale-your-impact.notion.site/27dd9c6ba679804b80a7ce439d56c91a?pvs=105🧬 Stop second-guessing your CMC strategy. Get an investor-ready CMC roadmap in 2 weeks, before mistakes cost you $2M+ and 18 months of delays. Secure your spot at https://stan.store/SmartBiotech/p/dont-let-cmc-kill-your-funding-roundSupport the show

Viral vectors are the backbone of cutting-edge cell and gene therapies, delivering life-altering treatments to patients with genetic diseases. But making these biological delivery vehicles is a high-wire act: unpredictable, complex, and fraught with hurdles that traditional biologics manufacturers have never faced.While the world races toward next-generation therapies, the challenge of producing viral vectors at clinical and commercial scale threatens to leave patients waiting on the sidelines.Our guest on the Smart Biotech Scientist Podcast is Lucas Chan, a molecular and cell biologist with over two decades of hands-on experience in cell and gene therapy development. From his formative research at Imperial College London, where he pioneered novel viral vector cell lines, to building the UK’s first GMP clinical viral vector core and later founding CellVec Pte Ltd Asia Pacific CDMO in Singapore, Lucas is the go-to architect for manufacturing viral vectors where infrastructure barely exists.Along the way, he’s faced and overcome challenges few others could imagine.Here are three reasons this episode is a must-listen:Viral Vectors Demystified: Lucas breaks down a common misconception: viral vectors aren’t malignant viruses, but genetically disarmed delivery vehicles that can’t revert or replicate, making them safe tools for gene therapy.Manufacturing Mayhem Made Manageable: Unlike monoclonal antibodies and other biologics, viral vectors (and other cell and gene therapies) are made in living cells, leading to a level of process unpredictability and complexity where “everything, everywhere, all at once” applies. Success hinges on scientific acumen and attention to even the smallest detail, from raw materials to equipment parameters, to ensure patient safety and product quality.Pioneering in Uncharted Territory: Moving from London to Singapore, Lucas faced not just technical but regulatory and logistical challenges to founding Asia-Pacific’s first CDMO dedicated to viral vectors. His advice: engage regulators early, leverage local biomanufacturing strengths, and build multidisciplinary teams to transfer and scale bioprocess know-how.Curious how viral vector manufacturing can be reimagined to unlock the full promise of cell and gene therapies? Listen to this episode and gain unique insights into the science, strategy, and sheer determination needed to bring advanced therapies out of the lab and into the clinic.Connect with Lucas Chan:LinkedIn: www.linkedin.com/in/lucaschangtNext step:Book a 20-minute call to help you get started on any questions you may have about bioprocessing analytics: https://bruehlmann-consulting.com/callPreparing for your IND? We’re building a CMC Dashboard in Excel to help biotech founders track tasks, timelines, and risks in one place. Join the waitlist for early access at https://scale-your-impact.notion.site/27dd9c6ba679804b80a7ce439d56c91a?pvs=105🧬 Stop second-guessing your CMC strategy. Get an investor-ready CMC roadmap in 2 weeks, before mistakes cost you $2M+ and 18 months of delays. Secure your spot at https://stan.store/SmartBiotech/p/dont-let-cmc-kill-your-funding-roundSupport the show

Andreas Castan, a seasoned expert in bioprocessing at Cytiva, explores the nuances of continuous manufacturing. He challenges the notion that continuous processes automatically deliver productivity gains, revealing that operational complexities and media costs can offset savings. Regulatory hurdles remain despite FDA backing, stressing the need for strong QA measures. Andreas emphasizes strategic timing for adopting continuous methods and warns against blindly embracing technology. He advocates for tailored solutions, focusing on robustness and understanding production bottlenecks.

What if process intensification could transform your bioprocessing economics without the complexity most engineers fear? Getting 3x productivity gains and 30-150% titer increases once seemed reserved for Big Pharma's endless R&D budgets, but a strategic approach to technology selection is making these results achievable for companies of any size.In this episode, David Brühlmann speaks with Andreas Castan, a bioprocess veteran with over 25 years of industry experience who provides leadership and support to Cytiva's bioprocess business. Andreas brings deep expertise from directing upstream development at Swedish Orphan Biovitrum and extensive work in expression systems, process development, scale-up, and cGMP manufacturing across multiple therapeutic modalities.Why tune in? Here's your process engineer's roadmap:Process Intensification Economics Decoded: Andreas reveals the cost-benefit reality behind continuous vs fed-batch manufacturing, including real process economic modeling data showing why the differences aren't as dramatic as you'd expect and what factors actually drive your business case.Low-Hanging Fruit That Delivers: Skip the overhyped AI solutions. Andreas shares the strategic fundamentals that work: high-producing cell line development, N-1 perfusion for rapid productivity gains, and smart bioreactor turndown strategies that eliminate process steps without adding complexity.Decision Framework for Technology Selection: Learn when continuous processing makes economic sense (and when it doesn't), how media costs impact your COGS analysis, and why understanding your bottlenecks, not following industry trends, should drive your intensification strategy.Industry Insider Strategies: Get the inside track on what AstraZeneca, Sanofi, Merck, Lonza, and Takeda are actually implementing, plus Andreas's perspective on why human expertise and mechanistic insights still outweigh AI in real-world process decisions.Ready to make smarter technology investments and achieve measurable productivity gains? This isn't theory. It's a practical guide to process intensification economics that you can apply whether you're preparing for Phase I or scaling for commercial manufacturing.Connect with Andreas Castan:LinkedIn: www.linkedin.com/in/andreas-castan-91570b1Cytiva landing page: Process intensificationOnline tool: Process intensifierNext step:Book a 20-minute call to help you get started on any questions you may have about bioprocessing analytics: https://bruehlmann-consulting.com/callPreparing for your IND? We’re building a CMC Dashboard in Excel to help biotech founders track tasks, timelines, and risks in one place. Join the waitlist for early access at https://scale-your-impact.notion.site/27dd9c6ba679804b80a7ce439d56c91a?pvs=105🧬 Stop second-guessing your CMC strategy. Get an investor-ready CMC roadmap in 2 weeks, before mistakes cost you $2M+ and 18 months of delays. Secure your spot at https://stan.store/SmartBiotech/p/dont-let-cmc-kill-your-funding-roundSupport the show

Discover why early planning for CMC is crucial for biotech founders aiming for regulatory success. Learn a proven five-step framework that can cut IND timelines significantly. Smart founders prioritize strategic partnerships over technical details, allowing them to maintain control while navigating complexity. Find out how Quality by Design transforms regulatory challenges into competitive advantages. Plus, get insights on operational tools like a Notion dashboard to streamline your CMC processes. Embrace these strategies to gain the upper hand in the biotech race!

Think you can crack the science first and worry about CMC when you "need it"? That's exactly how promising therapies die in regulatory limbo while patients keep waiting.Your breakthrough discovery means nothing if it's trapped in CMC chaos. While you're perfecting your molecular mechanism, competitors with inferior science but superior CMC strategy are racing past you to IND filing and ultimately, to patients.In this episode, I, David Brühlmann, your usual host, expose the dangerous delusion that's quietly bankrupting biotech startups: the belief that brilliant science automatically translates to successful drug development. Drawing from years of watching founders burn through millions because they treated CMC as an afterthought, I reveal why the smartest scientific minds often make the most catastrophic business decisions.Here's the hard truth you'll confront in this episode:The $50M Misconception: Why "CMC is just manufacturing" thinking destroys companies before they ever reach Phase II. While you're debating molecular targets, smart founders are building systematic CMC advantages that compress timelines and slash costs. The FDA doesn't care how elegant your science is if you can't demonstrate consistent, scalable manufacturing.The Brutal Mathematics of Delay: Systematic CMC approach: 10-12 months to IND, 85% hit timelines. "Figure it out later" approach: 15 months or more, and a much lower success rate. Every month you delay isn't just burning cash. If your therapy could help 10,000 patients annually, that's 833 people per month who don't get treatment because of preventable delays.Three Founder Myths That Kill Programs: The misconceptions about CMC being "basically just manufacturing," bringing in experts "when we need them," and CDMOs handling "the complicated stuff." Each myth leads to the same outcome: brilliant science trapped by business incompetence.Your Four-Action Emergency Protocol: Stop hoping CMC will work out. Start implementing systematic approaches. I give you four specific actions to execute this week, not someday when you're "ready," but right now while you can still prevent the crisis that kills 40% of biotech programs.The competitive reality: While you're listening to this episode, your biggest competitor just moved closer to IND filing. Maybe they completed process validation. Maybe they locked in analytical methods. The question isn't whether CMC matters. It's whether you'll master it before your competitors do.Next step:Book a 20-minute call to help you get started on any questions you may have about bioprocessing analytics: https://bruehlmann-consulting.com/callPreparing for your IND? We’re building a CMC Dashboard in Excel to help biotech founders track tasks, timelines, and risks in one place. Join the waitlist for early access at https://scale-your-impact.notion.site/27dd9c6ba679804b80a7ce439d56c91a?pvs=105🧬 Stop second-guessing your CMC strategy. Get an investor-ready CMC roadmap in 2 weeks, before mistakes cost you $2M+ and 18 months of delays. Secure your spot at https://stan.store/SmartBiotech/p/dont-let-cmc-kill-your-funding-roundSupport the show

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?Carmen Jungo Rhême is Full Professor at the University of Applied Sciences in Fribourg (HEIA-FR) and Director of the Biofactory Competence Center (BCC). With 17 years in the pharmaceutical industry at companies like Lonza, Merck Serono, UCB Farchim, and CSL Behring, she specializes in bioprocess development, protein purification, scale-up, and technology transfer. Since joining HEIA-FR in late 2023, she has launched research projects tackling antimicrobial resistance, sustainable food production, and bioprocess digitalization.Here are three reasons why this episode is a must-listen:A Blueprint for Scalable Bioprocessing: Carmen reveals the structured, four-phase approach the BCC uses to help startups and established companies alike, from feasibility and risk assessment, to scalable process design, tailored analytics, and seamless tech transfer to GMP manufacturing.The Future-Proof Skill Set: Discover why data management, digital tool adaptability, and systems thinking are non-negotiable skills for biotech professionals in the next five years and how both newcomers and seasoned scientists can level up.Bioprocessing as Design, Not Chaos: Learn how shifting your mindset from reactive to proactive, and from “biology is messy” to “biology is designable,” can unlock robust processes, faster innovation, and truly sustainable solutions.Ready to smarten up your biotech game? Listen in as Carmen and David unpack practical, actionable strategies for mastering modern bioprocessing—no matter your starting point.Connect with Carmen Jungo Rhême:LinkedIn: www.linkedin.com/in/carmenjungoWebsite: www.heia-fr.ch/en/applied-research/bcc/Next step:Book a 20-minute call to help you get started on any questions you may have about bioprocessing analytics: https://bruehlmann-consulting.com/call🧬 Stop second-guessing your CMC strategy. Get an investor-ready CMC roadmap in 2 weeks, before mistakes cost you $2M+ and 18 months of delays. Secure your spot at https://stan.store/SmartBiotech/p/dont-let-cmc-kill-your-funding-roundSupport the show