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

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