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

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

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What if you could predict formulation failures before ever touching a pipette? Computational approaches are revolutionizing biologics development, replacing trial-and-error experimentation with predictive intelligence that catches stability issues early and accelerates your path from candidate selection to clinic.

In this episode, David Brühlmann welcomes Giuseppe Licari, Principal Scientist in Computational Structural Biology at Merck KGaA. A chemist by training, Giuseppe transitioned from wet lab experimentation to the predictive power of in silico modeling. Today, he operates at the intersection of computational biology and CMC development, using digital tools to screen candidates for developability, predict formulation challenges, and de-risk development programs before committing resources to the lab.

Discover how computational methods are transforming the way biotech companies approach developability assessment and formulation strategy:

• Why maximizing shelf life isn’t always necessary in early development phases (02:56)
• The critical role of communication between computational and bench scientists (06:46)
• Core properties to assess for developability, including hydrophobicity, aggregation, charge, and immunogenicity (11:06)
• How accurate are in silico predictions, and where do they add the most value? (13:23)
• The limitations and strengths of machine learning and physics-based models in predicting protein behavior (15:19)
• The differences between developability, formulation development, and formulatability, and the value of early cross-functional collaboration (17:17)
• When to use platform formulations and when tailored approaches are needed for complex molecules (19:25)
• The advantages of using computational methods at any stage, especially for de-risking strategies (20:13)

Listen in for practical strategies for integrating in silico predictions into your developability and CMC workflows, catching stability issues before the lab, and making smarter development decisions that save time, material, and money.

Connect with Giuseppe Licari:

LinkedIn: www.linkedin.com/in/giuseppe-licari

Next step:

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What happens when cell therapy innovation meets real patient urgency? In this conversation, the barriers between scientist and patient all but vanish, bringing clarity—and a new sense of mission—to some of the biggest problems facing advanced therapy manufacturing and delivery.

Meet Jesús Zurdo, a biotech leader whose three decades of experience in innovation took on a whole new perspective when he became a leukemia patient himself. Seamlessly straddling the worlds of industry and patient care, Jesús Zurdo brings a refreshingly honest, systems-level view to cell therapies, manufacturing bottlenecks, and the realities of getting therapies from the lab to bedside.

Topics discussed:

• Experiences and lessons from stem cell registries and point-of-care manufacturing models (03:15)
• Challenges and potential of autologous and allogeneic cell therapies, including scalability and accessibility (06:08)
• The promise and limitations of in vivo cell therapy, delivery risks and patient safety (07:06)
• Reflections on current trends in manufacturing automation, delivery platforms, and the risk of overengineering (09:49)
• Barriers to wider adoption of advanced cell therapies, including hospital infrastructure and economic constraints (13:31)
• The case for earlier lines of treatment with new modalities and value in learning from actual patient experiences (14:30)
• The importance of integrating voices of patients, clinicians, and developers when solving complex problems (17:31)
• Why urgency and remembering our future roles as patients should guide therapy development (18:51)

Ready for bioprocessing to serve patients, yours included? For more insights and hands-on support, please subscribe so you never miss the next perspective-shifting episode.

Connect with Jesús Zurdo:

LinkedIn: https://www.linkedin.com/in/jesuszurdo

Email: [email protected]

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Real progress in cell and gene therapy shouldn’t be measured solely by scientific innovation, but by whether those innovations actually reach the patients who need them most.

In this episode, David Brühlmann sits down with Jesús Zurdo, a scientist who’s spent three decades engineering life-changing biotechnologies, but whose outlook on the field shifted dramatically after becoming a leukemia patient himself.

With experience on both sides of the system, Jesús Zurdo brings a rare, unfiltered perspective to the persistent gap between scientific promise and real-world patient access.

Here’s why this conversation will reshape the way you think about bioprocessing, scale-up, and the meaning of “patient-centric” innovation:

• The challenges of scaling up advanced therapies beyond just volume: shifting from “how much can we make” to “how many patients can we reach?” (00:21)
• Jesús Zurdo’s personal journey—from biotech innovator to patient—and how it reshaped his thinking on product design and patient needs (04:12)
• How the biotech industry often overemphasizes automation, cost of goods, and new technologies at the expense of true patient access (08:02)
• The importance of designing products and manufacturing processes with patients’ lived experience in mind—not just clinical metrics (05:43)
• Why the business model and value proposition of therapies may need to change to address the high cost and limited accessibility of new treatments (12:09)
• Lessons from point-of-care manufacturing and real-world delivery of cell therapies—speed versus perfection (09:11)
• How patient involvement in both development and long-term outcome tracking could drive better treatments and wider adoption (15:10)
• The limitations of current clinical trial endpoints and the need to integrate patient-reported outcomes and new data sources like wearables (17:10)

Real progress in biotech isn’t just about scientific breakthroughs, it’s about ensuring those advances reach the millions who need them most.

Let’s rethink our business models and deployment strategies to bridge this gap for real-world impact

Connect with Jesús Zurdo:

LinkedIn: https://www.linkedin.com/in/jesuszurdo

Email: [email protected]

Next step:

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From pandemic-speed vaccine deployment to AI-powered process control, what separates hype from real manufacturing transformation?

The biotech industry faces a fundamental challenge: how do you maintain rigorous quality standards while accelerating development timelines, personalizing therapies, and adopting transformative technologies? The answer isn't found in chasing every innovation trend, it's in understanding which changes create genuine value and when to implement them across the product lifecycle.

Irina Ramos brings a perspective earned through high-stakes execution. After leading the global technology transfer of AstraZeneca's COVID-19 vaccine, a project that compressed typical timelines while maintaining uncompromising quality standards, she's applying those lessons to the industry's next wave of challenges: phase-appropriate CMC strategy, the practical realities of AI integration, and building teams that bridge generational experience gaps in an era of rapid technological change.

This conversation cuts through the noise. Irina discusses when continuous processing actually makes strategic sense (hint: it's not always the right answer), why AI in bioprocessing requires more human expertise rather than less, and the collaborative frameworks that enabled one of the fastest vaccine rollouts in history—lessons directly applicable to your current CMC challenges.

Episode highlights:

• How the biotech community is constantly changing, and the importance of adaptability for future scientists (00:00)
• Navigating phase-appropriate CMC strategy: What to focus on in early clinical phases and which decisions set the foundation for compliance (02:36)
• Scenarios for switching from batch to continuous processing, including barriers and benefits for early-stage vs. established products (02:58)
• Lessons from leading AstraZeneca's COVID-19 vaccine technology transfer: Collaboration, rapid regulatory communication, and mission-driven teams (05:20)
• Adapting lessons from the pandemic for ongoing drug development—balancing speed and risk while maintaining quality (08:24)
• Realistic perspectives on integrating AI in bioprocessing: demystifying its applications, emphasizing human-critical oversight, and practical use cases in manufacturing (10:40)
• Key skills for scientists in a biotech world shaped by AI—why foundational understanding and strong mentorship matter (13:51)
• Bridging experience gaps: How to foster collaboration and creativity between new and established professionals in regulated environments (15:45)
• Final takeaway: Start small, remain mission-driven, and remember that one size does not fit all in continuous manufacturing (17:15)

Whether you're evaluating process platform decisions for Phase I programs, building cross-functional teams for tech transfer, or determining which digital tools deserve investment beyond the buzzword, this episode provides decision frameworks grounded in real-world execution at global scale.

Connect with Irina Ramos:

LinkedIn: www.linkedin.com/in/irinaramos

Next step:

Need fast CMC guidance? New on-demand CMC advisory → Learn more here

Book a 20-minute call to help you get started on any questions you may have about bioprocessing analytics: https://bruehlmann-consulting.com/call

Free 5-day email course, The CMC Failure Chain: the five recurring CMC mistakes that put your promising program at risk → Get it here

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The biotech industry operates under constant tension: we work with products that directly impact human lives, demanding rigorous controls and validation at every step. Yet standing still means falling behind. The question isn't whether to innovate, it's how to do it without compromising the quality and safety standards that define our industry.

Irina Ramos has lived this paradox throughout her career. As a downstream processing leader who's guided CMC programs from early development through global regulatory filings, she helped orchestrate the worldwide transfer of AstraZeneca's COVID-19 vaccine—a masterclass in balancing speed, scale, and uncompromising quality standards. Now, she's championing a vision that sounds almost radical: lights-out biomanufacturing facilities where continuous processes run at steady state with minimal human intervention.

In this conversation, Irina shares the unfiltered reality of building innovation cultures in conservative environments, the surprising drivers behind continuous processing adoption, and why the industry's careful nature isn't a barrier to transformation. It's the foundation for sustainable innovation.

Discussion highlights:

• Why conservatism is vital in biotech—and how to balance it with innovation (00:00)
• The vision for "lights-out" manufacturing and if bioprocess facilities could run with minimal human intervention (02:50)
• Irina Ramos's career story and the lessons her "happy accidents" teach junior scientists (03:53)
• Mindset shifts: Transitioning from scientist to innovation leader in CMC development (06:29)
• Building an innovation culture in a conservative, highly regulated industry (08:07)
• Essential mindsets for scientists to thrive and innovate in biotech environments (11:22)
• Coordination strategies for effective communication across stakeholders, departments, and geographies (13:52)
• The misconceptions of continuous manufacturing and what actually drives its adoption (17:09)
• What's hot in continuous biomanufacturing: trends, global perspectives, and how real-time analytics can change process control (21:12)
• Guiding principles for choosing between hybrid or end-to-end continuous processes (23:46)
• Practical tips on implementing control strategies and real-time monitoring in manufacturing (25:01)

If you're navigating the shift from batch to continuous processing, leading cross-functional innovation initiatives, or wondering how to advocate for new technologies without disrupting validated processes, this episode offers practical frameworks you can apply immediately.

Connect with Irina Ramos:

LinkedIn: www.linkedin.com/in/irinaramos

Next step:

Need fast CMC guidance? New on-demand CMC advisory → Learn more here

Book a 20-minute call to help you get started on any questions you may have about bioprocessing analytics: https://bruehlmann-consulting.com/call

Free 5-day email course, The CMC Failure Chain: the five recurring CMC mistakes that put your promising program at risk → Get it here

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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.

Connect with Tom Rizzo:

LinkedIn: www.linkedin.com/in/thomas-rizzo-4a0a6314/

Contact email: [email protected]

Isospec Analytics website: www.isospecanalytics.com

Free 5-day email course, The CMC Failure Chain: the five recurring CMC mistakes that put your promising program at risk → Get it here

Support the show

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]

Isospec Analytics website: www.isospecanalytics.com

Next step:

Need fast CMC guidance? New on-demand CMC advisory: Get 20 expert answers/month in 1 day + monthly strategy call. → Learn more: https://stan.store/SmartBiotech/p/ondemand-cmc-expertise-for-biotech-founders

Free 5-day email course, The CMC Failure Chain: the five recurring CMC mistakes that put your promising program at risk → Get it here

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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-jungnelius

Cytiva website: www.cytivalifesciences.com/en/us

Next step:

Need fast CMC guidance? New on-demand CMC advisory: Get 20 expert answers/month in 1 day + monthly strategy call. → Learn more: https://stan.store/SmartBiotech/p/ondemand-cmc-expertise-for-biotech-founders

Book a 20-minute call to help you get started on any questions you may have about bioprocessing analytics: https://bruehlmann-consulting.com/call

Free 5-day email course, The CMC Failure Chain: the five recurring CMC mistakes that put your promising program at risk → Get it here

Support the show

Your Manufacturing Decisions Are Costing You More Than You Think

Every 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-jungnelius

Cytiva website: www.cytivalifesciences.com/en/us

Next step:

Need fast CMC guidance? New on-demand CMC advisory: Get 20 expert answers/month in 1 day + monthly strategy call. → Learn more: https://stan.store/SmartBiotech/p/ondemand-cmc-expertise-for-biotech-founders

Book a 20-minute call to help you get started on any questions you may have about bioprocessing analytics: https://bruehlmann-consulting.com/call

Free 5-day email course, The CMC Failure Chain: the five recurring CMC mistakes that put your promising program at risk → Get it here

Support the show