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

• 208: Cryogenic Infrared Ion Spectroscopy: From Mass Spec Limitations to Molecular Precision with Tom Rizzo - Part 2

  What if you could analyze every metabolite, glycan variant, and unknown impurity in your bioprocess sample—not just the targets you're looking for, but everything that's actually there? Cryogenic infrared ion spectroscopy combined (CIRIS) with AI-powered analysis transforms untargeted screening from aspiration to reality.This episode moves from fundamental principles to practical applications. While Part 1 established how CIRIS overcomes mass spectrometry's structural limitations, Part 2 reveals what becomes possible when you can definitively identify complex mixtures: better mAb characterization, earlier disease detection, and process decisions based on complete data rather than educated guesses.Professor Tom Rizzo returns to discuss Isospec Analytics' path from laboratory innovation to commercial service platform. His transition from academic leadership at EPFL to biotech entrepreneurship offers insights for any scientist considering whether breakthrough research deserves a startup—and what that journey actually requires.For bioprocess scientists drowning in unidentified peaks, struggling with glycan heterogeneity, or making critical manufacturing decisions with incomplete analytical data, this conversation demonstrates how next-generation analytics powered by quantum chemistry and machine learning can illuminate what's been hidden in your samples all along.Episode Highlights:Why targeted metabolomics creates a "streetlight effect"—and how untargeted CIRIS analysis reveals the complete molecular landscape (00:00)Isomer-specific glycan characterization for mAbs: distinguishing structural variants that impact efficacy and immunogenicity (03:17)Advanced disease detection and biomarker discovery: identifying diagnostic signatures in complex biological matrices (05:21)AI meets quantum chemistry: automated spectral library building and machine learning algorithms that accelerate molecule identification from hours to seconds (06:05)From data generation to decision-making: how comprehensive analytics and AI transform bioprocess development workflows (09:23)Isospec's commercial roadmap: service platform for comprehensive sample analysis and projected timeline for benchtop instrumentation (10:09)Academic to entrepreneur: Tom Rizzo's perspective on leaving tenure for a startup, with practical advice for scientists evaluating the leap (12:05)Personal motivation behind early diagnostics: cancer and leukemia experiences that drive Isospec's clinical applications (14:11)Technical deep dive: messenger tagging methodology and achieving single-ion infrared detection sensitivity (15:41)The transformative capability: adding a structural dimension to mass spec data that eliminates ambiguity in complex mixture analysis (17:55)Mass spectrometry tells you what masses are present. Cryogenic infrared ion spectroscopy tells you what molecules they actually are. When coupled with AI-powered analysis, this combination enables truly comprehensive characterization—from process impurity identification to critical quality attribute assessment to early disease biomarker discovery.If you're making bioprocess decisions with incomplete analytical information, managing glycan complexity in biologics development, or exploring how emerging analytical technologies could solve your toughest characterization challenges, this episode provides both the technical foundation and the commercial pathway forward.🧬 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

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• 207: Cryogenic Infrared Ion Spectroscopy: From Mass Spec Limitations to Molecular Precision with Tom Rizzo - Part 1

  What if you could identify every structural variant in your biologics—without ambiguity, without massive sample requirements, and without the guesswork that plagues traditional mass spectrometry? Cryogenic infrared ion spectroscopy (CIRIS) makes it possible, transforming molecular characterization from frustrating puzzle to precise science.Today's guest, Professor Tom Rizzo, bridges the gap between academic innovation and industrial application. As former Dean of the School of Basic Sciences at EPFL in Lausanne and now Chief Scientific Officer at Isospec Analytics, Tom has spent over two decades developing analytical techniques that solve problems conventional methods can't touch.His journey from a childhood fascination sparked by chemistry demonstrations at the 1964 New York World's Fair to pioneering a breakthrough technology reveals both the persistence required for true innovation and the pathway from laboratory curiosity to commercial reality. For bioprocess scientists struggling with glycan characterization, isomer identification, or any structural puzzle where mass spec alone falls short, this conversation offers both validation and solutions.Episode Highlights:The fundamental limitations of current biomolecular analysis methods and why innovation is critical (02:51)From World's Fair chemistry demos to laser spectroscopy: Tom Rizzo's path to analytical innovation (03:31)The two-decade quest to combine mass spectrometry sensitivity with laser spectroscopy precision—and the machine that finally made it work (04:26)Why Tom transitioned from academic leadership to Isospec Analytics: bringing lab techniques to production environments (09:17)CIRIS fundamentals: how cooling ions to 10 Kelvin unlocks molecular fingerprints that room-temperature methods miss (11:14)CIRIS advantages for biologics: single-ion sensitivity, isomer discrimination, and unique molecular "fingerprints" for definitive identification (14:25)Integrating CIRIS into existing bioprocess workflows: LC-MS compatibility and the path to commercial instrumentation (17:29)Hard-won lessons from translating academic breakthroughs into industrial tools (17:43)When mass spectrometry hits its limits—distinguishing isomers, characterizing glycans, identifying unknowns in complex mixtures—cryogenic infrared ion spectroscopy provides the structural resolution you need. This isn't incremental improvement; it's a fundamental expansion of what's analytically possible.If you're facing molecular identification challenges that conventional methods can't solve, or if you're curious how next-generation analytical techniques will transform bioprocess development, this episode delivers actionable insights from a scientist who's lived both the innovation and implementation journey.Connect with Tom Rizzo:LinkedIn: www.linkedin.com/in/thomas-rizzo-4a0a6314/Contact email: [email protected] Analytics website: www.isospecanalytics.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/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

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• 206: Process Economics Decoded: How to Model Biomanufacturing Costs From Clinical to Commercial Scale with Niklas Jungnelius - Part 2

  Carbon neutrality goals are everywhere in biopharma. But how do you actually measure and reduce your true environmental impact when data gaps and baseline differences make comparisons so tough?In this episode, David Brühlmann talks with Niklas Jungnelius, Cytiva’s expert in process modeling and sustainability, who’s spent years uncovering what really drives emissions and how small process tweaks can deliver big results.Niklas goes beyond the numbers, challenging assumptions and showing how sustainability becomes a strategic, data-driven advantage. From real-world cases at Cytiva, he explains why recycling plastics may not move the needle and why the real gains often lie in hotspots like cleanroom energy use and raw material choices.Here’s why this episode will make you rethink your next facility upgrade:Understanding life cycle assessment and the key damage categories in environmental sustainability, including carbon emissions, water usage, and resource depletion. (00:00)The challenge of defining carbon emissions baselines and why it’s harder, and often more expensive, to achieve deep reductions if your operations already use clean energy sources. (03:06)Why the focus on recycling single-use plastics may not be the most effective route for lowering emissions, and what truly drives carbon footprint in bioprocessing. (05:54)The impact of production scale, consumables, and obscure chemicals on the overall environmental impact and how these surprises can shift sustainability strategies. (06:20)Practical advice for scientists and engineers: How to start monitoring and modeling environmental impact in process development and manufacturing. (08:00)The importance of involving manufacturing perspectives early in process development, and choosing the right level of detail and ambition for process modeling. (08:18)There’s no one-size-fits-all in manufacturing technology—whether fed-batch, continuous, or hybrid and decisions must fit each organization’s needs, resources, and ambitions. (10:13)Industry trends that could transform the field, from intensified fed-batch production to future technologies like cell-free expression systems. (11:22)Where to connect with Niklas for further questions or collaboration. (14:03]Whether you’re an early-stage startup, a strategic advisor, or on the front lines of bioprocess development, this episode invites you to rethink your sustainability strategy and modeling approach. Check out the below links to connect with Niklas Jungnelius and additional resources.Connect with Niklas Jungnelius:LinkedIn: www.linkedin.com/in/niklas-jungneliusCytiva website: www.cytivalifesciences.com/en/usNext 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

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• 205: Process Economics Decoded: How to Model Biomanufacturing Costs From Clinical to Commercial Scale with Niklas Jungnelius - Part 1

  Your Manufacturing Decisions Are Costing You More Than You ThinkEvery bioreactor decision. Every scale-up choice. Every facility investment. They're all silently writing checks your process might not be able to cash.The difference between a profitable biologics program and one that bleeds capital? Process economic modeling, the analytical framework that reveals exactly where your money goes and why.In this episode of the Smart Biotech Scientist Podcast, David Brühlmann talks with Niklas Jungnelius, Process Modeling Leader at Cytiva, who has spent 25+ years decoding the economics of biologics manufacturing for biotech companies navigating billion-dollar decisions.Niklas reveals the hidden cost drivers most teams miss, the surprising economics behind fed-batch vs. continuous processing, and why your facility choice at intermediate scale could make or break your business case.Episode Highlights:What process economic modeling is and how it differs from mechanistic modeling (06:40)Main cost drivers in biologics and biosimilars manufacturing, and their direct and indirect impacts on patient pricing (09:21)The role of manufacturing scale and productivity in driving down costs, and how facility type (stainless steel vs single-use) affects labor, flexibility, and investment (11:51)Trade-offs between single-use and stainless steel facilities at intermediate production scales (15:07)Key differences in cost and efficiency between fed-batch and fully continuous manufacturing, including productivity limitations and capital/expenditure implications (16:20)The impact of resin lifetime and under-utilization on clinical manufacturing costs (19:51)Hidden or less quantifiable costs such as facility flexibility, excess capacity, safety margins, and the importance of realistic assumptions in economic modeling (20:20)This is a grounded discussion with practical takeaways for biotech scientists seeking clarity in the complex terrain of process economics. Part two of this conversation will focus on sustainability modeling and the latest technologies reshaping bioprocessing economics.Ready to see how process modeling could transform your approach and protect your bottom line? Listen to the episode and rethink your next investment.Connect with Niklas Jungnelius:LinkedIn: www.linkedin.com/in/niklas-jungneliusCytiva website: www.cytivalifesciences.com/en/usNext 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

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• 204: Mastering CRO Selection: Essential Questions for CMC Analytical Development with Daniel Galbraith - Part 2

  Cell and gene therapies are transforming modern medicine, but their path to market is fast and complex. They often jump from small trials to global launch at record speed, putting pressure on analytics, supply chains, and partnerships. Success depends on making smart choices about what to build in-house and what to entrust to expert partners.Daniel Galbraith knows these challenges intimately. With decades of hands-on experience and as Chief Scientific Officer at Solvias, Daniel has witnessed firsthand the seismic shifts in analytical development for advanced therapies. He’s been on every side of the table: troubleshooting manufacturing snags, scaling up from a single batch to hundreds per month, and guiding companies as they choose between in-house development and relying on a CRO’s muscle.In this episode:How evolving cell and gene therapy timelines are driving the need for true CRO-drug developer partnerships (00:00)The unique challenges of scaling CMC analytics from early trials to global commercialization (02:51)Key pitfalls to avoid when outsourcing to CROs—especially around communication, scheduling, and troubleshooting (06:26)Deciding whether to build capabilities in-house or outsource to a CRO, and how to find the right balance for your team (08:41)The critical importance of strong project management for juggling relationships between developer, CRO, and CDMO (09:51)Daniel's perspective on the future of combination therapies and what the analytical landscape will demand of CROs (13:33)Practical advice for building transparent, open CRO partnerships that support your goals (15:21)Facing scale-up challenges or a first CGT launch? This conversation shares practical strategies to advance therapies efficiently.Tune in for actionable insights on CMC, outsourcing, and analytical development.Connect with Daniel Galbraith:LinkedIn: www.linkedin.com/in/daniel-galbraith-26a6138Solvias website: www.solvias.comEmail: [email protected] 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? Grab our Startup Founder CMC Dashboard in Notion to help you track tasks, timelines, and risks in one place at https://stan.store/SmartBiotech/p/discovertoind-cmc-dashboard-for-startup-founders🧬 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

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