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

When every batch belongs to a single patient, a single centralized facility cannot serve the world. In Part 2, Chantale Bernatchez moves from process development into the broader consequences of that reality: the manufacturing model built around clinical proximity, the global alliance bringing TIL production to regions with no current access, and the next-generation engineered approaches redefining what these therapies can do.
Chantale Bernatchez is Head of Process Development at CTMC, a joint venture between Resilience and MD Anderson Cancer Center. If you missed Part 1, she explained how specific activation changes recovered a failing TIL process from 50% to 95% success in heavily pre-treated patients.
Topics discussed:
How close collaboration with MD Anderson accelerates clinical development and regulatory readiness (03:08)
CTMC’s approach to process development and adapting to innovative technologies (05:15)
The value of partnership-based models versus traditional CDMO-driven approaches (06:24)
Global technology transfer: building alliances to expand access to cell therapies, with a case study in Brazil (07:35)
Key barriers and solutions for cell therapy manufacturing in new regions (09:41)
Practical advice for scientists starting in GMP manufacturing and process development (10:46)
Future directions in CAR T and TIL, including logic-gated CARs, engineered TILs, and in vivo therapies (12:24)
The importance of continued innovation and collaboration to expand global patient access (17:39)
Smart insight:
The choice of manufacturing partner in cell therapy is not a logistics decision. It is a process development decision. CTMC's collaboration-based model exists because many early-stage developers arrive without a process robust enough to hand over. For scientists in small or mid-sized companies, engaging that kind of partnership too late, or on purely transactional terms, is one of the most avoidable risks in early clinical development.
If you’re interested in exploring further the concepts we touched on, such as cell therapy manufacturing, process control, and scaling living therapies—take a look at these related discussions:
Episodes 125 - 126: How to Enhance Cell Engineering Using Mechanical Intracellular Delivery with Armon Sharei
Episodes 109 - 110: Spinning Like Earth: Designing Low-Shear Bioreactors for Better Cell Culture with Olivier Detournay
Episodes 105 - 106: From Proteins to Cell Therapy: Why ATMPs Aren’t Just Complex Biologics with Oliver Kraemer
Connect with Chantale Bernatchez:
LinkedIn: www.linkedin.com/in/chantale-bernatchez-22b09511
CTMC website: www.ctmc.com
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The most underappreciated parameter in cell therapy process development is not your bioreactor, your media, or your activation protocol. It is the patient. Chantale Bernatchez has spent 20 years learning that lesson the hard way, watching the same manufacturing process succeed brilliantly with one donor and fail completely with the next. In this episode, she explains why starting material variability is the defining challenge of cell therapy manufacturing, and what it actually takes to build a process robust enough to survive it.
Chantale Bernatchez is Head of Process Development at CTMC, a joint venture between Resilience and MD Anderson Cancer Center. She holds a PhD in immunology and has spent two decades advancing T cell therapy from early research programs at MD Anderson to GMP-compliant clinical manufacturing. She holds four patents in adoptive cell therapy.
Key topics discussed:
Personal journey: from immunology PhD in Quebec to cell therapy leadership in Houston (04:25)
Evolution of TIL therapy at MD Anderson, including manufacturing innovations to overcome declining T cell yields (06:14)
The fundamental differences between traditional medicines and cell-based immunotherapies (10:01)
Unique manufacturing complexities for autologous therapies, including batch variability and process standardization (11:19)
Strategies to address decreased cell fitness in heavily pretreated patients, including changes in cell activation and culture conditions (13:57)
Key learnings from the CAR T and TIL manufacturing process: balancing process duration, cell fitness, and product yield (16:28)
Mechanistic differences between CAR T and TIL therapies and their implications for efficacy and resistance (17:58)
The limits and risks of automation in cell therapy manufacturing—balancing manual vs. automated processes (24:04)
Why moving between manufacturing platforms raises challenges in comparability and clinical outcomes (25:44)
The ongoing search for critical cell quality attributes that correlate with patient response (27:00)
In part two, Chantale goes deeper into next-generation approaches, technology transfer, and what needs to change to broadly expand patient access.
Smart insight: In cell therapy, manufacturing isn’t just a production step. It defines the therapy itself. Because each patient’s starting cells are unique, even subtle changes in the process can significantly alter clinical outcomes.
If you’re interested in exploring further the concepts we touched on—such as cell therapy manufacturing, process control, and scaling living therapies—take a look at these related discussions:
Episodes 125 - 126: How to Enhance Cell Engineering Using Mechanical Intracellular Delivery with Armon Sharei
Episodes 109 - 110: Spinning Like Earth: Designing Low-Shear Bioreactors for Better Cell Culture with Olivier Detournay
Episodes 105 - 106: From Proteins to Cell Therapy: Why ATMPs Aren’t Just Complex Biologics with Oliver Kraemer
Connect with Chantale Bernatchez:
LinkedIn: www.linkedin.com/in/chantale-bernatchez-22b09511
CTMC website: www.ctmc.com
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Getting an NDA signed shouldn't take weeks. If your CRO needs more than 48 hours to start the paperwork, your project timeline is already moving in the wrong direction.
Ron Najafi knows what rigorous analytical work actually looks like under pressure. As founder and CEO of Emery Pharma, he led the investigation that identified NDMA as a degradation product of ranitidine — findings the FDA formally validated and that reshaped how the industry approaches nitrosamine risk assessment. In Part 2, he moves from that scientific foundation into the operational questions that determine whether a CRO partnership accelerates your program or quietly slows it down.
If you haven't heard Part 1, it covers Ron's career arc and the technical details of nitrosamine contamination in pharmaceutical development. This episode stands on its own for anyone focused on CRO selection, bioanalytical strategy, and what three decades of building analytical companies actually teaches you.
Topics discussed:
How to tell if a CRO’s workflow is robust—or just rigid (05:51)
The importance of method validation and product stability testing (07:27)
Managing expectations and trust-building in client relationships (08:29)
Entrepreneurial lessons: raising capital, team-building, and finding the right partners (10:00)
The hidden costs of public vs. private biotech ventures (12:31)
Reducing bioanalytical costs in biologics through mass spectrometry (13:23)
The future of analytical workflows and personalized medicine (14:48)
Smart insight:
In biotech, success isn’t just about the science—it’s about strategic discipline. Ron emphasizes a few hard-earned principles: raise more capital than you think you’ll need, don’t fixate on valuation, and invest in smart, creative talent. Just as important, real value is unlocked through strong partnerships and the ability to manage collaborations and acquisitions with intention.
If this topic resonates with you, here are a few related episodes on building strong CMC foundations and avoiding costly development mistakes:
Episodes 231 - 232: From IND to BLA: The Biologics CMC Decisions That Determine Regulatory Success with Henri Kornmann
Episodes 203 - 204: Mastering CRO Selection: Essential Questions for CMC Analytical Development with Daniel Galbraith
Episodes 199 - 200: Mastering Quality by Design: From Product Failures to Commercial Success in Biologics CMC Development
Episodes 189 - 190: Why Smart Biotech Founders Plan CMC First (While Competitors Burn Cash Later)
Episodes 139 - 140: Regulatory Secrets Revealed: Why Your CMC Strategy Could Make or Break Your Biotech Startup with Rivka Zaibel
Episodes 57 - 58: Crafting a Solid CMC Strategy: Key Factors and Common Pitfalls with Matthias Müllner
Episodes 23 - 24: Strategies for Success: Master CMC Development with Gene Lee
Connect with Ron Najafi:
LinkedIn: www.linkedin.com/in/ronnajafi
Emery Pharma: www.emerypharma.com
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When drug safety fails, patients and entire markets pay the price. Understanding your CMC isn't just compliance — it's the line between therapeutic promise and product recall.
Ron Najafi has lived that reality firsthand. As founder of NovaBay Pharmaceuticals and Emery Pharma, he spent decades building companies at the intersection of analytical chemistry and drug development. His investigation into nitrosamine contamination in ranitidine — which led the FDA to formally validate Emery Pharma's findings — remains one of the most consequential episodes in recent pharmaceutical quality history.
In Part 1, Ron traces the scientific and entrepreneurial path that led him there, and shares what CMC teams working in drug development need to understand about impurity risk before it becomes a regulatory crisis.
Episode highlights:
Early academic experiences and inspirations that Ron Najafi to a science career (05:46)
Challenges and milestones in building companies like CP Lab Safety and NovaBay Pharmaceuticals (07:59)
The invention and impact of the ECO Funnel® on lab safety and environmental responsibility (12:01)
The formation of Emery Pharma following industry setbacks and lessons in adaptation (17:03)
The fundamentals of impurity risk analysis, especially nitrosamine contamination in pharmaceuticals (20:56)
The ranitidine (Zantac) NDMA discovery, its investigation, and consequences for drug regulation (23:33)
Common sources of nitrosamine and practical advice for bioprocess risk management (27:51)
Differences in impurity risk between small molecule and biologic drug processes (28:03)
The necessity and regulatory expectation of impurity and leachable/extractable analysis (30:07)
Smart insight:
One of Ron's clients conducted a superficial nitrosamine risk assessment, proceeded to manufacturing, and spent approximately $6 million producing three batches. At final FDA-required testing, NDMA came back at 11,000 nanograms per pill against an acceptable daily intake limit of 96 nanograms. The batches were unusable.
A thorough risk assessment run earlier would have cost a fraction of that. If you are developing a drug with secondary or tertiary amines in your process and have not yet conducted a formal nitrosamine risk assessment, that is the one action to take after listening to this episode.
If this topic resonates with you, here are a few related episodes on building strong CMC foundations and avoiding costly development mistakes:
Episodes 231 - 232: From IND to BLA: The Biologics CMC Decisions That Determine Regulatory Success with Henri Kornmann
Episodes 203 - 204: Mastering CRO Selection: Essential Questions for CMC Analytical Development with Daniel Galbraith
Episodes 199 - 200: Mastering Quality by Design: From Product Failures to Commercial Success in Biologics CMC Development
Episodes 189 - 190: Why Smart Biotech Founders Plan CMC First (While Competitors Burn Cash Later)
Episodes 57 - 58: Crafting a Solid CMC Strategy: Key Factors and Common Pitfalls with Matthias Müllner
Episodes 23 - 24: Strategies for Success: Master CMC Development with Gene Lee
Connect with Ron Najafi:
LinkedIn: www.linkedin.com/in/ronnajafi
Emery Pharma: www.emerypharma.com
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Shear sensitivity is the silent challenge behind many advanced biomanufacturing modalities. Orbital-shaken bioreactors—often underestimated—may be a key enabler your CMC development is missing.
Tibor Anderlei, CSO at Kühner Shaker, joined David Brühlmann on the Smart Biotech Scientist Podcast to unpack the hidden physics behind bioprocess reproducibility and next-generation shaking technology. He has seen firsthand how overlooking fundamental parameters can derail scale-up and delay development timelines. In his role, Tibor is responsible for the customer interface—spanning sales, service, support, GMP topics, troubleshooting, marketing, and applied technology—with a focus on orbital shaking technology and small-scale cultivation support.
Topics discussed:
The importance of measuring oxygen transfer rate (OTR) and carbon dioxide transfer rate (CTR) for reproducible bioprocesses—why DO is not sufficient (02:55)
Real-time process analytical technology (PAT) for small-scale bioreactors, including microtiter plates and shake flasks (06:47)
Pre-culture reproducibility: transferring at the right OTR and its impact on main cultures (07:56)
Price sensitivity and scale-up challenges in cultivated meat—implications for media and equipment selection (10:36)
Expansion of shaking technology to fields such as mixing, storage, and thawing, including applications in liquid crystal production (12:10)
Leadership lessons from competing with bigger players: how smaller companies stay innovative, agile, and close to their customers (14:20)
The significance of strong business partner relationships and trusting gut feeling in decision-making (16:32)
Key advice for smart biotech scientists: careful definition of screening conditions and the use of online measurement tools at small scale (18:09)
Accessible resources for mastering shaken bioreactor techniques, including webinars and direct contact with Tibor Anderlei (19:38)
Smart insight:
Treat small-scale shaken systems as real bioreactors and define screening conditions carefully from the start. Using online measurement tools even at early stages provides critical visibility and helps ensure that results are reproducible and scalable.
Building a robust scale-up strategy requires looking at the process from multiple angles—regulatory, digital, and operational. Listen to those previous episodes:
Episode 03 - 04: How to Master Biotech Scale-up Without Guesswork with Leonardo Sibilio
Episode 25 - 26: 9 Critical Steps for a Seamless Transition to Large-Scale Production
Episode 231-232: From IND to BLA: The Biologics CMC Decisions That Determine Regulatory Success with Henri Kornmann
Episode 233-234: Why Most Bioprocess Automation Projects Fail with Anthony Catacchio
Episode 237-238: High-Throughput Microbial Screening with Sebastian Blum
Connect with Tibor Anderlei:
LinkedIn: www.linkedin.com/in/tibor-anderlei-66342411/
Kühner Shaker website: www.kuhner.com
Shaking Technology Forum: www.shakingtechnology.com
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