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

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-26a6138

Solvias website: www.solvias.com

Email: [email protected]

Next steps:

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

Preparing 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

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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Finding an analytical CRO that's truly invested in your success, not just processing samples, makes all the difference in CMC development. In this episode, host David Brühlmann talks with Daniel Galbraith, Chief Scientific Officer at Solvias, about the essential questions and mindset that lead to breakthrough CRO partnerships.

With nearly three decades in analytical development, spanning monoclonal antibodies, biosimilars, and cell and gene therapies, Daniel reveals what separates CROs who become true partners from those who just run methods. His insights can save your program months of delays and costly missteps.

Key Topics Discussed:

• Why cell and gene therapies face unique challenges compared to the progression seen with monoclonal antibodies (03:04)
• Daniel’s career path: from entering biotech in 1996 to CSO at Solvias, and the rapid evolution of the industry (05:00)
• The analytical hurdles in characterizing cell-based products and how their inherent variability impacts development (09:46)
• Approaches to analytical method requirements for autologous cell therapies, and how data is gathered iteratively in these cases (13:02)
• The biggest obstacles to scaling up cell and gene therapies, and why innovative cell manipulation technologies are needed (16:06)
• Current trends in therapeutic modalities: why antibody-drug conjugates stand out, and whether mRNA therapies are losing momentum (18:37)
• Practical advice on choosing an analytical CRO as a strategic partner - what to look for, what questions to ask, and why enthusiasm and standardization matter (21:55)

Wondering how to streamline your own analytical strategy, or navigate the parallel universe of cell and gene therapy development? Dig into this episode for Daniel’s insider perspective. Then consider how the right analytical partnership could accelerate your path to clinic.

Connect with Daniel Galbraith:

LinkedIn: www.linkedin.com/in/daniel-galbraith-26a6138

Solvias website: www.solvias.com

Email: [email protected]

Next steps:

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

Preparing 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

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 the answer to battling antibiotic-resistant infections isn’t a new antibiotic, but harnessing viruses that have been quietly dominating bacterial populations?

Bacteriophages, viruses that target and kill bacteria, have been saving lives for a century, but their true potential is only now being unlocked by modern machine learning. The race isn’t just about discovering effective phages; it’s about deploying the right therapy, personalized to the patient, before time runs out.

On this episode, David Brühlmann welcomes José Luis Bila, Co-Founder and CEO of Precise Health. Driven by personal tragedy and an engineer’s mindset, José is shaping a future where AI-powered phage therapy isn’t a niche solution, but a scalable, accessible weapon against the superbugs that evade antibiotics. From building bioreactor capacity to navigating regulatory gray zones, José brings a rare blend of technical vision and practical urgency to a problem that affects families and health systems worldwide.

Key topics discussed:

• The challenge of evolving bacteria and phages, and the question of whether it’s possible to keep up with nature’s pace through engineering new phages in silico (00:00)
• Overview of bacteriophage production: complexity, types of bioreactors used, and comparison with chemical synthesis (02:54)
• Bioproduction logistics: using CDMOs vs. in-house hospital production and the real-world timescales for manufacturing (02:32)
• Barriers for smaller or less funded hospitals, especially in low- and middle-income countries, with thoughts on hospital infrastructure differences worldwide (04:41)
• Creative solutions for cost-effective phage production in remote and underserved regions, such as the potential for single-use or mobile bioreactors (06:01)
• Why downstream processing and ensuring product purity is a bottleneck; the need for miniaturization and economic scalability (06:40)
• Parallels and differences in downstream processing between bacteriophages and viral vectors (09:15)
• The vital role of stability and shelf life for phage therapy logistics and economic viability (09:15)
• Regulatory pathways for phage therapy in Europe and beyond, including magistral preparations, ethical approvals, and adapting to digital tools for selection (12:39)
• The future vision: routine clinic entry through matching existing phage libraries, with longer-term goals of engineering bespoke phages via AI when necessary (15:52)
• José’s perspective on building global infrastructure and making phage therapy cost-effective and universally accessible (18:08)

José Bila’s message: solutions to antimicrobial resistance are within reach. The biotech community must build accessible infrastructure, using AI and innovative systems to ensure phage therapy benefits reach every patient, everywhere.

Connect with José Luis Bila:

LinkedIn: www.linkedin.com/in/josé-luis-bila-phd-3b08a5a7

Precise Health SA: www.precisehealth.io

Interested in how scientists are fighting superbugs? Learn how phage therapy and smart bioprocess design are helping outmaneuver drug-resistant pathogens. Check out this interview with one of our previous guests!

Episodes 187-188: From Biology Is Messy to Designable: The Smart Bioprocessing Transformation with Carmen Jungo Rhême

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

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

Antibiotic resistance isn’t just a looming problem. It’s a global crisis. Every year, more than one million people die directly from resistant infections, and another 5 million die indirectly. Routine infections are becoming life-threatening, and healthcare systems worldwide are under pressure.

Despite decades of warnings, pharmaceutical solutions are falling behind, while “superbugs” continue to outpace new drug development. If trends continue, by 2050, antibiotic resistance could claim 10 million lives annually and cost the world $1 trillion.

Meet José Luis Bila, a chemist-turned-biotech-founder, who transformed personal tragedy into a mission to disrupt this deadly status quo. After losing both parents to antibiotic-resistant infections, José dedicated his career to the search for targeted, effective alternatives. Now, as Co-Founder and CEO of Precise Health SA, he’s building AI-powered bacteriophage therapy platforms that promise to revolutionize personalized infection treatments and outmaneuver today’s most stubborn bacteria.

Why tune into this episode? Here are three standouts from José’s story and his technical playbook:

• José's personal story: Losing both parents to antibiotic resistance and its impact on his career path. (00:00)
• Scope of the antibiotic resistance crisis: Global deaths, indirect impacts, and economic cost projections. (06:29)
• Why big pharma is pulling out of antibiotic development and why innovation may come from smaller startups. (07:29)
• Why antibiotic resistance persists: Static nature of antibiotics versus adaptable bacteria, and misuse of antibiotics. (09:45)
• Introduction to bacteriophage therapy and its specificity challenges. (11:46)
• The current slow, manual process for matching phages to infections and its limitations in urgent clinical settings. (13:08)
• How machine learning is being used at Precise Health to rapidly identify and source the right phages using genetic information. (16:58)
• The potential to reduce phage matching and delivery time from months to just days, and how smart batching and regional surveillance improve economics. (17:23)

José Luis Bila’s journey shows the power of science driven by purpose. Through persistence, he’s pioneering AI-driven phage therapy - offering precision, hope, and a potential lifeline in the fight against antibiotic-resistant infections.

Connect with José Luis Bila:

LinkedIn: www.linkedin.com/in/josé-luis-bila-phd-3b08a5a7

Precise Health SA: www.precisehealth.io

Interested in how scientists are fighting superbugs? Learn how phage therapy and smart bioprocess design are helping outmaneuver drug-resistant pathogens. Check out this interview with one of our previous guests!

Episodes 187-188: From Biology Is Messy to Designable: The Smart Bioprocessing Transformation with Carmen Jungo Rhême

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

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 process works perfectly at two-liter bench scale. Then you hit fifty liters and titer drops 20%. By two hundred liters, aggregation appears and charge variants shift. Your management team asks: "How long to fix this?" The honest answer? Three to twelve month, because you're flying blind.

In Part 2 of this Quality by Design Master Class, David Brühlmann reveals why scale-up chaos isn't inevitable. It's a solvable engineering problem. Drawing on experience leading bioprocess innovation at Merck and guiding biotech companies through CMC development, David delivers the process control framework that transforms reactive troubleshooting into predictive manufacturing.

The core truth: eighty percent of quality problems stem from twenty percent of your process variables. David shows how to identify Critical Process Parameters, implement intelligent control strategies, and leverage hybrid modeling that reduces experiments by 60-80%. With case studies from Genentech and Amgen, you'll gain the blueprint that turns QbD requirements into competitive advantage.

Part 1 taught you what to build and measure. Part 2 shows you how to control your process to consistently deliver commercial-scale quality.

Topics Discussed:

• The common pitfalls of scaling up manufacturing from bench to production, and why process control must go beyond end-product testing (02:10)
• Overview of the QbD framework: Quality Target Product Profile (QTPP), Critical Quality Attributes (CQAs), and the focus of this episode - Control Strategies for manufacturing (05:00)
• Identifying and monitoring Critical Process Parameters (CPPs) and their impact on quality, with real-world examples from Genentech’s monoclonal antibody platform (08:20)
• Structure of an effective manufacturing control strategy: Input, process, and output controls - including practical details on real-time monitoring and release testing (11:00)
• The role of hybrid modeling and machine learning in accelerating process optimization, and how this approach can dramatically reduce the experimental burden (13:30)
• Real examples of improved outcomes and efficiency through model-based control strategies, and why training and process understanding are essential for team success (16:10)
• A quick, actionable exercise biotech teams can use to map process risks and identify critical control points (16:55)

Whether you’re part of a start-up or a large biotech firm, this episode offers clear, strategic steps for implementing QbD and improving process reliability. Don’t forget to listen to Part 1 for more on QTPP and CQA, and visit www.bruehlmann-consulting.com for additional resources.

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

Preparing 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

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

Over 40% of biotherapeutic failures during clinical development stem from stability problems—and most trace back to protein aggregation that could have been prevented. In this episode of the Smart Biotech Scientist Podcast, David Brühlmann exposes the hidden manufacturing crisis that derails promising biologics programs and delivers the systematic Quality by Design framework that elite biotech companies use to build quality into every process step.

David brings two decades of bioprocess expertise from his time leading technology innovation at Merck and now guiding emerging biotech companies through CMC development as Managing Director of Brühlmann Consulting. Drawing on FDA and EMA regulatory guidance as well as landmark industry case studies he transforms complex QbD principles into an actionable roadmap for IND submission.

This isn't theoretical regulatory compliance. It's competitive survival. Companies implementing these QbD foundations achieve predictable manufacturing scale-up, accelerated regulatory approval, and significant cost advantages. If your team is navigating CMC development for the first time or struggling with scale-up challenges, this episode provides the blueprint to transform process uncertainty into manufacturing confidence.

What You’ll Learn in This Episode:

• The high clinical failure rate for biologics due to protein aggregation and stability problems, and one company’s costly lesson in the scale-up phase. (00:00)
• An introduction to Quality by Design (QbD)—how it differs from traditional development and why “the process is the product” in biologics. (03:09)
• The three foundational pillars of QbD, with today’s focus on product understanding and quality requirements. (05:46)
• Constructing your Quality Target Product Profile (QTPP): what to include and why starting with the patient is key. (07:05)
• A real-world QTPP example—the AMAP case study—and how it shaped formulation, packaging, and critical quality standards. (09:45)
• Defining and prioritizing Critical Quality Attributes (CQAs): measuring what truly matters for safety and efficacy. (11:50)
• Lessons from Roche/Genentech’s QbD journey: regulatory insights and the business value of robust CQA identification. (15:55)
• The “CQA Reality Check” exercise: a step-by-step method to focus your team on attributes that impact patients. (21:05)
• How early, candid dialogue with regulators and using management tools like the Notion CMC Dashboard can streamline the development roadmap and reassure investors. (23:30)

Ready to flip the odds in your favor and make QbD your competitive edge? Stream this episode to catch actionable strategies and real-world cautionary tales that could change your CMC development playbook for good.

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

Preparing 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

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 happens when the most complex molecules in biotech meet the organizational challenge of managing 300+ analytical scientists? The answer lies not just in the science, but in building systems that turn technical complexity into reliable delivery.

In Part 2 of our deep dive with Amanda Hoertz, VP of Analytical and Formulation Sciences at KBI Biopharma, we shift focus from the molecular intricacies of ADCs to the operational mastery required to scale analytical development across multiple sites. Amanda reveals how her team achieves consistency across hundreds of scientists while maintaining the agility to pivot priorities in real time when critical programs need emergency support.

This isn't just about managing people; it's about architecting systems that preserve institutional knowledge, accelerate method transfer, and deliver results when regulatory deadlines loom.

What you'll discover:

• Seamless Project Handoffs Without Knowledge Loss: How KBI's stable team assignments eliminate the costly learning curves that plague most CDMO relationships, ensuring your molecule expertise stays with your program from development through commercial manufacturing.
• Organizational Scale Without Operational Chaos: The decision tree and layered reporting structure that allows 200+ analysts at a single site to function as a coordinated force, capable of rapid reprioritization and flood-level resource deployment when programs reach critical status.
• Digital Transformation That Actually Works: Beyond the automation buzzwords, Amanda walks through the practical realities of LIMS/ELN implementation, audit-compliant systems, and machine learning databases that transform raw data into defensible, actionable insights for complex biologics.

Whether you're evaluating how analytical capabilities scale with program complexity, or seeking practical insights into leading technical teams through digital transformation, this episode delivers the operational intelligence that separates successful ADC programs from expensive failures.

Connect with Amanda Hoertz:

LinkedIn: www.linkedin.com/in/amanda-hoertz-3aba605

KBI Biopharma: www.kbibiopharma.com

KBI Portal: www.standalone.kbi.bio

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

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 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-3aba605

KBI Biopharma: www.kbibiopharma.com

KBI Portal: www.standalone.kbi.bio

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

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 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-14984811

Website : www.biochromatographix.com

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

Preparing 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

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

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-14984811

Website : www.biochromatographix.com

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

Preparing 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

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