210 - How AI Is Rewriting GMP: Smarter CAPA, PAT, DOE, and Continuous Yield
As AI becomes more integrated into pharmaceutical manufacturing, the question is not just how fast we can adopt it, but how safely. In this episode, Ben Locwin and Subhi Saadeh discuss the intersection of AI, GMP, and Quality 4.0, exploring both the promise and the challenges of applying intelligent systems in regulated environments.Key topics covered:- Current applications of AI in GMP, including CAPA and deviation management- The role of validation and why algorithmic opacity poses regulatory challenges- How Process Analytical Technology (PAT) enables real-time release decisions- The importance of Design of Experiments (DOE) for process optimizationContinuous manufacturing and how yield can signal process performanceChapters00:00 Introduction to AI in Pharma00:40 Current Applications of AI in GMP02:32 Challenges and Validation in AI03:22 Process Analytical Technology (PAT)09:50 Design of Experiments (DOE) in Pharma13:27 Continuous Manufacturing Explained15:40 Yield Calculation in Manufacturing22:12 Conclusion and Contact InformationBen Locwin is a Healthcare Executive, MMA fighter, Jiu Jtisu pro and Quality and Regulatory SME working in medical devices, pharma and other regulated industries.Subhi Saadeh is a Quality Professional and host of Let's Combinate. With a background in Quality, Manufacturing Operations and R&D he's worked in Large Medical Device/Pharma organizations to support the development and launch of Hardware Devices, Disposable Devices, and Combination Products for Vaccines, Generics, and Biologics. Subhi serves currently as the International Committee Chair for the Combination Products Coalition(CPC) and as a member of ASTM Committee E55 and also served as a committee member on AAMI's Combination Products Committee.For questions, inquiries or suggestions please reach out at letscombinate.com or on the show's LinkedIn Page.
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209 - ALCOA++ EXPLAINED | What Everyone Gets Wrong About Data Integrity with Monika Andraos
In this episode, I talk with Monika Andraos of Dunamis Compliance about how organizations can navigate group think and approach data integrity the right way. We cover risk culture, CSV vs. data integrity, ALCOA++, data governance, and practical tips for newcomers. Key topics include: • Encouraging diverse perspectives to combat group think • Why data integrity is broader than CSV • The pyramid structure: data integrity at the top, CSV & validation as elements • ALCOA++ and traceability in real-world systems • Practical CSV and validation workflows • Common audit pitfalls and how to strengthen governance⏱ Timestamps00:00 – Intro: Group Think & Risk Appetite00:41 – Data Integrity in Consulting01:41 – Encouraging Diverse Perspectives02:37 – CSV vs Data Integrity03:13 – The Role of Data Stewards03:54 – The Pyramid: Data Integrity, CSV & Validation04:45 – ALCOA++ and Core Data Integrity Elements13:59 – Real Examples: CSV & Validation Workflows17:40 – Common Audit Pitfalls & Data Governance22:50 – Advice for Newcomers + Wrap-UpMonika is the Principal at Dunamis Compliance. She has over a decade of experience in formulating and executing strategies for data integrity and data governance assessments and remediation, risk management and computerized system validation within the pharmaceutical sector. She has worked within Quality, Technical Operations, Automation and Regulatory Affairs to execute and deliver compliant system solutions in regulated GXP environments.
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208 - How Drugs Are Designed, Targets, Phenotypes, and Structure Based Design
In this episode, Jesse Gordon-Blake, PhD, delves into the intricacies of medicinal chemistry, particularly focusing on drug discovery for ALS (amyotrophic lateral sclerosis). Jesse explains the process of discovering molecules that modulate biological pathways, the difference between structure-based and phenotype-based drug design, and the role computational methods play in drug development. The conversation also explores the challenges of crossing the blood-brain barrier, the importance of validating target response, and the complexities of progressing from a theoretical compound to preclinical studies. Additionally, Jesse touches on the significance of target product profiles, CNS drug design characteristics, and the iterative nature of medicinal chemistry. He concludes by discussing his current projects at Cortex, including fundraising strategies and timelines for drug development.00:00 Introduction to Medicinal Chemistry00:37 Drug Discovery Approaches02:01 Computational Methods in Medicinal Chemistry03:21 Challenges in ALS Drug Discovery04:23 Blood-Brain Barrier and Drug Design05:29 Key Properties for CNS Drug Design08:58 Day-to-Day in Drug Discovery09:45 Early Stage Drug Development12:28 Validating Drug Targets16:15 From Theory to Animal Testing22:46 Funding and Timeline Considerations25:45 Regulatory and Manufacturing Considerations28:32 Conclusion and Contact InformationDr. Jesse Gordon-Blake is an independent biotechnology and drug discovery consultant with expertise in medicinal chemistry and neurotherapeutics. He has led efforts in small molecule and peptide therapeutic development, AI-enabled drug discovery, and biotech startup formation, and currently serves as the CSO of Cortexa Therapeutics. He earned his PhD in Medicinal Chemistry from the University of Illinois at Chicago, focusing on developing innovative small-molecule enzyme modulators for Alzheimer’s disease.https://www.linkedin.com/in/jesse-gordon-blake-phd-52a26274/https://www.cortexatherapeutics.com/Subhi Saadeh is a Quality Professional and host of Let's Combinate. With a background in Quality, Manufacturing Operations and R&D he's worked in Large Medical Device/Pharma organizations to support the development and launch of Hardware Devices, Disposable Devices, and Combination Products for Vaccines, Generics, and Biologics. Subhi serves currently as the International Committee Chair for the Combination Products Coalition(CPC) and as a member of ASTM Committee E55 and also served as a committee member on AAMI's Combination Products Committee.For questions, inquiries or suggestions please reach out at letscombinate.com or on the show's LinkedIn Page.
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207 - What 99.999% Reliability Really Means
In this episode, Subhi Saadeh sits down with Alan Stevens, CAPT, to break down the concept of five nines (99.999% reliability) in medical devices. They cover where the standard came from, why FDA introduced it in their 2020 draft guidance, and what it means for life-saving products like epinephrine and naloxone injectors.Alan explains how manufacturers can demonstrate reliability through fault tree analysis, robust process controls, and challenge testing—without needing impossible sample sizes.If you work in pharma, medtech, or quality, this episode will help you understand what “five nines” really means and how to meet FDA expectations while ensuring patient safety.Chapters00:00 – What is Five Nines Reliability?Intro to 99.999% and why it matters for medical devices.00:33 – FDA Guidance & Common Misconceptions2020 draft guidance, sample size myths, and industry confusion.01:17 – How to Demonstrate ReliabilityFeasibility, practical approaches, and FDA expectations.02:31 – High-Stakes Use CasesEpinephrine, naloxone, glucagon injectors.04:00 – Fault Tree Analysis ExplainedBreaking down failures and linking to design/manufacturing.05:25 – Why FDA Chose Five NinesBalancing feasibility, safety, and ISO 14971 influences.09:02 – Verification vs. ReliabilityDesign verification testing vs. true reliability demonstration.23:16 – Key Takeaways for IndustryClosing thoughts on meeting and maintaining reliability standards.Alan Stevens CAPT is the Global Head of Complex Devices and Drug Delivery Systems at AbbVie within the RA Emerging Technologies, Devices and Combination Products team. Prior to joining AbbVie, Alan spent 20 years at the FDA/CDRH leading premarket review and policy development for drug delivery devices and combination products.Subhi Saadeh is a Quality Professional and host of Let's Combinate. With a background in Quality, Manufacturing Operations and R&D he's worked in Large Medical Device/Pharma organizations to support the development and launch of Hardware Devices, Disposable Devices, and Combination Products for Vaccines, Generics, and Biologics. Subhi serves currently as the International Committee Chair for the Combination Products Coalition(CPC) and as a member of ASTM Committee E55 and also served as a committee member on AAMI's Combination Products Committee.For questions, inquiries or suggestions please reach out at letscombinate.com or on the show's LinkedIn Page.
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23:35
206 - Will AI Decide Your Next Drug/Device Approval?
Artificial Intelligence is moving fast but how do you regulate it in industries where precision and risk management are everything?In this episode of Let’s Combinate, Subhi Saadeh sits down with Dominick Romano, founder of Drainpipe.io, to unpack the future of AI in pharma, medtech, and drug/device regulation. The conversation goes deep into how AI could reshape dossier preparation, regulatory submissions, and quality oversight — and what strategies regulators and companies need to make sure speed doesn’t come at the cost of trust.We explore:- Why pharma’s unique risk profile makes AI regulation different from other industries-How ICH guidelines and process validation can be applied to AI systems-What “combinatorial problem sets” mean for pharma and AI models-The role of AI in regulatory affairs and dossier preparation-How regulators may use AI to accelerate reviews and approvals-The balance between speed, accuracy, and zero hallucinations in regulatory contexts-The future of AI in quality control, biologics, and beyondIf you work in pharma, medtech, or drug/device combination products, this episode will give you a clear look at how AI could change your world and what needs to happen before it earns the regulator’s trust.Episode Chapters00:00 Introduction: Regulating AI in Pharma/MedTech01:01 Pharma’s Unique Risk Profile02:14 AI in Regulatory Affairs03:44 Combinatorial Problem Sets in Pharma04:24 ICH Guidelines and AI Regulation08:22 Process Validation in AI10:20 AI in Regulatory Submissions15:54 Ensuring Accuracy and Consistency17:02 Regulatory Agencies and AI18:28 Accelerating Drug Approval with AI21:36 Time Savings in Dossier Formation25:44 AI in Quality Control for Biologics27:42 Challenges in AI Integration29:25 The Future of Pharma & MedTech with AI30:40 Where to Find Dominick RomanoDominick Romano is the founder and CEO of Drainpipe.io, focused on building trustworthy AI systems for regulated industries like pharma and medtech. A graduate of Full Sail University in video game development, his career spans game design, programmatic advertising, and voice applications before moving into AI. He was named one of Technology Innovators’ Top 50 AI CEOs and has contributed to global initiatives such as the WHO/ITU AI for Health program. Today, he helps organizations explore how AI can be validated and integrated without compromising compliance or trust.Subhi Saadeh is a Quality Professional and host of Let's Combinate. With a background in Quality, Manufacturing Operations and R&D he's worked in Large Medical Device/Pharma organizations to support the development and launch of Hardware Devices, Disposable Devices, and Combination Products for Vaccines, Generics, and Biologics. Subhi serves currently as the International Committee Chair for the Combination Products Coalition(CPC) and as a member of ASTM Committee E55 and also served as a committee member on AAMI's Combination Products Committee.For questions, inquiries or suggestions please reach out at letscombinate.com or on the show's LinkedIn Page.
Hello Combi-Nation!
Our industry fee complicated sometimes. Drugs, devices, clinical trials, submissions, sterilization validation, design control, risk management, market access reimbursement, the list goes on.
My name is Subhi Saadeh. I've spent over a decade in medical device, pharma, and combination product development. My goal is mastery, so this podcast is to ask questions I have to people who may have the answers.
Whether you're background is Pharma, Device or both, I invite you to listen and together we can simplify by Combinating!
Ireland