Let's Combinate - Drugs + Devices

ICH Q13 explains how pharmaceutical companies can apply batch definition, traceability, control strategy, validation, release, and lifecycle management to continuous manufacturing of drug substances and drug products.Learn more:https://www.letscombinate.comSchedule a call:https://calendly.com/letscombinate/let-s-combinate-intro-sessionIn this episode, Subhi Saadeh explains ICH Q13 and the key concepts behind continuous manufacturing in pharmaceutical manufacturing.The core question behind ICH Q13 is simple:How do you apply traditional quality concepts like batch definition, traceability, control strategy, validation, release, and lifecycle management when the manufacturing process does not stop?This episode covers the major Q13 concepts, including the difference between batch and continuous manufacturing, how batches can be defined in continuous manufacturing, the three continuous manufacturing models described in the guideline, residence time distribution (RTD), disturbance handling, control strategy, validation, release, and lifecycle management.Subhi also discusses why batches still matter in continuous manufacturing. Even when a process operates as a continuous flow, batches remain essential for traceability, investigations, trending, stability programs, release decisions, and recalls.Key topics covered:• What ICH Q13 is and why it matters• Batch manufacturing versus continuous manufacturing• Why manufacturers still need batch definitions• Time-based, mass-based, and campaign-based batch definitions• The three continuous manufacturing models described in ICH Q13• Residence Time Distribution (RTD)• Why RTD matters for traceability and investigations• Disturbance impact assessment and material disposition• Control strategy considerations for startup, steady-state operation, and disturbances• The role of Process Analytical Technology (PAT)• Disturbance management using magnitude, duration, and frequency• Validation considerations for continuous manufacturing• Release strategies supported by process understanding and monitoring• Lifecycle management and risk-based change controlTimestamps:00:00 ICH Q13 Overview00:48 Why Batches Matter01:21 Batch vs. Continuous Manufacturing01:59 Defining Batches02:48 Three Continuous Manufacturing Models03:54 Residence Time Distribution (RTD)06:05 Control Strategy Basics07:19 Disturbance Handling08:19 Validation, Release, and Lifecycle Management10:16 Wrap-Up and Next StepsSource referenced in this episode:ICH Q13: Continuous Manufacturing of Drug Substances and Drug ProductsFinal version adopted 16 November 2022https://database.ich.org/sites/default/files/ICH_Q13_Step4_Guideline_2022_1116.pdfReferences to ICH Q13 guideline and are included for educational commentary and discussion.Questions or feedback?📧 [subhi@letscombinate.com](mailto:subhi@letscombinate.com)🌐 https://www.letscombinate.comSubhi Saadeh is the Founder and Principal at Let’s Combinate, where he helps teams develop and control drug-device combination products by aligning quality systems, development, manufacturing, and regulatory expectations across drug and device domains. He is a consultant, auditor, trainer, and speaker with experience across Pfizer, Gilead Sciences, and Baxter, supporting the development and launch of vaccines, biologics, generics, medical devices, and drug-device combination products.

In this episode, Subhi breaks down Q11 by focusing on three key sections: how the drug substance process is developed, where that process begins, and how it is controlled.He places Q11 in context with Q7 for API GMP, Q8 for pharmaceutical development, Q9 for quality risk management, and Q10 for the pharmaceutical quality system. The episode covers Section 3 on manufacturing process development, Section 5 on starting materials, and Section 6 on control strategy beyond release testing.In the next episode, Subhi will cover ICH Q12.Timestamps00:00 ICH Q11 overview00:47 Drug substance basics01:14 Where Q11 fits in the ICH Quality framework02:15 Section 3: Manufacturing process development03:26 Linking drug substance quality to drug product quality04:25 Section 5: Starting materials05:41 Section 6: Control strategy06:11 Wrap-up and next episodeSubhi Saadeh is the Founder and Principal at Let’s Combinate, where he helps teams develop and control drug-device combination products by aligning quality systems, development, and regulatory expectations across drug and device domains. He is a consultant, auditor, trainer, and speaker with experience across Pfizer, Gilead, and Baxter, supporting the development and launch of combination products across vaccines, biologics, and generics.

his episode looks at where Q10 fits in the broader quality landscape, including its roots in ISO 9001, ISO 9004, and ISO 13485, while making the key distinction that Q10 is not a certifiable ISO-style standard. Instead, Q10 is designed to augment regional GMPs and provide a lifecycle model for managing pharmaceutical quality.Using the Annex 2 PQS diagram, Subhi walks through how Q10 applies across pharmaceutical development, technology transfer, commercial manufacturing, and product discontinuation. The episode discusses phase-appropriate GMP expectations, why Q10 does not replace GMP, and how management responsibility spans the full lifecycle, including outsourced activities and purchased materials.The episode also covers the four core PQS elements: process performance and product quality monitoring, CAPA, change management, and management review. These elements are presented as operational loops that help maintain control and drive improvement. Subhi also highlights the two key enablers of the model: knowledge management, connected to ICH Q8, and quality risk management, connected to ICH Q9.The episode closes with Section 4 of Q10, which focuses on continual improvement of the PQS itself, including management review inputs, external changes, resourcing, documentation, and communication.00:00 Welcome and Series Setup00:14 Why ICH Q10 Matters01:21 Lifecycle and Phase-Appropriate GMP02:23 GMP Foundation and the PQS Model02:58 Management Responsibility03:31 Core PQS Elements04:26 Enablers: Knowledge Management and QRM04:40 Guideline Walkthrough: Sections 1 to 306:37 Continual Improvement of the PQS07:45 Wrap Up and Next EpisodeSubhi Saadeh is the Founder and Principal at Let’s Combinate, where he helps teams develop and control drug-device combination products by aligning quality systems, development, and regulatory expectations across drug and device domains. He is a consultant, auditor, trainer, and speaker with experience across companies including Pfizer, Gilead, and Baxter, supporting the development and launch of combination products across vaccines, biologics, and generics, including leading and supporting combination product transformations across large organizations.

This episode continues the ICH Quality Series with an overview of ICH Q8 (Pharmaceutical Development), focusing on what it is, how it’s structured, and how to think about it in practice.ICH Q8 defines the suggested contents for CTD Section 3.2.P.2 and aims to harmonize how pharmaceutical development is presented in regulatory submissions. It primarily applies to drug product development and later-stage submissions, where a full understanding of the product and process is expected.The guideline is structured in three parts: the core sections, which outline development elements such as formulation, manufacturing, and container closure; the annexes, which introduce key Quality by Design concepts including QTPP, CQAs, risk assessment, design space, and control strategy; and a final section that explains how this information is organized across the CTD.The episode walks through the relationship between TPP and QTPP, defines critical quality attributes, explains how design space is established through prior knowledge, risk assessment, and experimental work such as design of experiments, and outlines how a control strategy is built across materials, process controls, monitoring, and testing.High Level QBD(4 min): https://www.youtube.com/watch?v=orlPpfQvb5kQBD vs. Design Controls: https://www.youtube.com/watch?v=W_LSD0kKQ3400:00 Introduction to ICH Q800:42 Related QbD Videos01:12 Structure of ICH Q802:28 Objective and Scope04:49 Annexes and QbD Concepts05:20 Quality Target Product Profile06:33 Critical Quality Attributes07:09 Design Space and DoE09:17 Control Strategy10:06 Submission and Wrap-UpSubhi Saadeh is the Founder and Principal at Let’s ComBinate, where he helps teams develop and control drug-device combination products by aligning quality systems, development, and regulatory expectations across drug and device domains.A consultant, auditor, and trainer, Subhi has worked across companies including Baxter, Pfizer, and Gilead, supporting the development, manufacturing, and launch of medical devices and combination products for vaccines, generics, and biologics.

ICH Q6 Explained: Specifications, Control Strategy, and What’s Changing in Q6(R1)In this episode of Let’s ComBinate, Subhi continues the ICH Q-series with ICH Q6 and explains why specifications are central to defining and controlling drug products and drug-device combination products.He breaks down how ICH Q6 formalizes: • what to test (attributes or CQAs tied to safety and efficacy) • how to test (methods and procedures) • what is acceptable (acceptance criteria or limits)All of which come together to support the release decision.He also covers the difference between ICH Q6A (small molecules) and ICH Q6B (biologics), highlighting the increased variability in biologics and the greater reliance on characterization and process understanding.Finally, he summarizes key themes from the 2024 ICH Q6(R1) concept paper, including: • alignment of shared principles across Q6A and Q6B • expanded scope to include new modalities and combination products • linkage to ICH Q12 lifecycle management and established conditions • a shift toward more science and risk based approaches with less reliance on routine batch testing⸻Key References • ICH Q6 Guidelines (Q6A and Q6B):https://www.ich.org/page/quality-guidelines • ICH Q6(R1) Concept Paper (2024):https://www.ich.org/page/quality-guidelines (navigate to Q6 revision concept paper)⸻Timestamps00:00 Intro to ICH Q600:36 Host background01:05 Why specifications matter01:49 Q6A vs Q6B overview02:33 Purpose of ICH Q602:59 What is a specification04:27 Q6 R1 update themes05:49 Lifecycle and risk based specifications06:29 Wrap up and next stepsSubhi Saadeh is the Founder and Principal at Let’s Combinate, where he helps teams develop and control drug-device combination products by aligning quality systems, development, and regulatory expectations across drug and device domains.

This is a lesson out of my ASQ CQA course with Andy Robertson, on how to write and classify audit findings.Access the full CQA course here: https://cqeacademy.teachable.com/p/the-cqa-master-class-courseI break down key terms like finding, nonconformity, observation, and noncompliance, and explains that everything must tie back to requirements and objective evidence. The episode covers when to write a nonconformity vs an observation, common severity levels (critical, major, minor), and how to structure clear findings. I also cover how to sequence audit results and where auditors often go wrong, especially when they insert opinion or recommend solutions.Timestamps00:00 Course preview00:42 Key audit terms01:56 What makes findings reportable04:16 Severity classification06:42 Writing findings07:57 Structuring reports10:38 Auditor boundariesSubhi Saadeh is a certified ISO 13485 Lead Auditor, CQE, and CQA with experience leading audits and building quality systems across medical devices and combination products at companies like Baxter, Pfizer, and Gilead Sciences. Through Let’s ComBinate, he focuses on bridging the gap between pharma and devices through educational content, industry collaboration, and consulting.

In this episode of Let’s Combinate, Subhi Saadeh speaks with Jen Riter about analytical method validation for drug device combination products. The discussion explores how traditional drug analytical validation under ICH Q2 differs from validating functional and mechanical performance methods used for combination products. These methods often require an engineering mindset that incorporates measurement system analysis (MSA), gage R&R studies, and the use of fabricated surrogate standards when devices cannot be reused for testing.They also discuss platform test methods and how standards such as ISO 11040 and other ISO references can serve as starting points for method development. The conversation touches on the evolving alignment between ISO based device methods and pharmacopeial expectations such as USP <382>. The episode also covers make vs buy testing decisions, when to outsource specialized testing such as CCIT and extractables and leachables, and how sponsors manage oversight of contract testing laboratories.Timestamps00:00 Welcome and Guest Introduction00:53 ICH Q2 vs MSA Mindset Shift04:37 Surrogate Standards for Mechanical Testing11:12 Platform Methods and ISO 1104015:14 ISO vs USP Verification Debate20:06 Outsourcing Analytical Testing Strategy24:07 Choosing the Right Test Lab26:20 Sponsor Oversight of Contract Labs30:09 Wrap UpAbout Jen RiterJen Riter is an analytical testing and laboratory leader with nearly three decades of experience working in pharmaceutical packaging, drug delivery systems, and combination products. She has held leadership roles at West Pharmaceutical Services and Kindeva Drug Delivery, where her work has focused on analytical method development, validation, and testing strategies for drug delivery systems and injectable combination products. She is also a contributor to the Combination Products Handbook, where she authored a chapter on analytical testing and method validation for combination products.About Subhi SaadehSubhi Saadeh is the Founder and Principal of Let’s Combinate BioWorks, where he helps companies close the gaps between drug and device development, quality systems, and regulatory expectations. He is a Certified Quality Auditor and ISO 13485 Lead Auditor with leadership experience at Baxter, Pfizer, and Gilead Sciences including responsibility for management and oversight of assemble label pack sites and working with device primary, secondary and tertiary packaging suppliers. Subhi previously chaired the Combination Product Working Group for Rx-360, served as International Committee Chair for the Combination Products Coalition, and served on AAMI’s Combination Products Committee. He also hosts the Let’s Combinate podcast and is a writer and speaker on quality at the intersection of drugs and devices.

Subhi Saadeh sits down with Georg Digel, founder of Elevate CAPA, to break down what should trigger CAPA, and how to investigate the right way using practical tools and better problem statements.Timestamps00:00 Welcome and Guest Intro00:53 The Hairiest CAPA Case03:02 Human Error Root Cause04:58 Common CAPA Misconceptions06:11 Why Root Cause Fails12:16 When to Open CAPA17:26 CAPA Inputs and Triggers19:28 One Process or Two22:28 How to Investigate Properly25:09 Tools for Root Cause26:20 Problem Statement Basics27:48 Wrap Up and Where to FindGeorg Digel is the founder of Elevate CAPA and works with medical device quality leaders to make nonconformance and CAPA systems faster, stronger, and more audit-ready. He brings hands-on experience from early work on the production line through roles across consulting, startups, and larger organizations, with a focus on root cause and investigation quality. He also shares practical NC and CAPA breakdowns and training content with the MedTech community. LinkedIn: https://www.linkedin.com/in/georgdigel/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.

In this episode of the ICH Q series, Subhi Saadeh covers ICH Q4, which focuses on pharmacopeial harmonization. He explains why ICH Q4 exists, the problem it was created to solve, and how the ICH Q4 framework, Q4A, Q4B, and the Q4B annexes work together to determine when pharmacopeial test methods are considered interchangeable across ICH regions. The episode also explains the role of the Pharmacopoeial Discussion Group (PDG) in technical harmonization and walks through practical examples, including ICH Q4B Annex 3.ICH Guidelines (Quality): https://www.ich.org/page/quality-guidelinesICH Q4B Annex 3(R1) – Tests for Particulate Contamination (Subvisible Particles): https://database.ich.org/sites/default/files/Q4B%20Annex%203%28R1%29%20Guideline.pdfTimestamps00:00 Introduction to the ICHQ Series00:03 What Pharmacopeial Harmonization Means00:42 Why ICH Q4 Exists01:55 ICH Q4 Framework and Structure02:54 Understanding Q4A, Q4B, and the Annexes03:59 Practical Examples (Particulates, Disintegration)08:05 Conclusion and Next StepsSubhi Saadeh is the Founder and Principal at 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.

In this episode of Let’s Combinate, host Subhi Saadeh breaks down the ICH Q2 guideline with a practical focus on analytical procedure validation. The discussion covers key definitions, core validation characteristics, and how ICH Q2 applies to drug delivery systems and drug-device combination products.Subhi explains how the revised ICH Q2 guideline aligns with ICH Q14 and what that alignment means for harmonizing analytical validation expectations across regions and regulatory authorities. The episode walks through key validation characteristics including accuracy, precision, specificity, linearity, and range, and clarifies the relationship between ICH Q2 and ICH Q14. Practical guidance is also provided on how to read and apply ICH Q2 efficiently, particularly for teams working with combination products.Timestamps00:00 Introduction to Let’s ComBinate00:42 Purpose and importance of ICH Q203:11 Scope and product coverage06:10 Key validation characteristics08:15 Practical application and reading ICH Q210:23 Conclusion and next stepsSubhi Saadeh is the Founder and Principal at 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.

In this episode of Let’s Combinate: Drugs + Devices, host Subhi Saadeh continues the Combinating with ICH series by breaking down how the International Council for Harmonisation (ICH) guidelines are organized and why that structure matters for drug and drug-device combination products.Subhi walks through the four main ICH guideline families, Quality (Q), Safety (S), Efficacy (E), and Multidisciplinary (M), and explains how each fits into the broader product lifecycle. The episode places particular emphasis on the Quality guidelines, which form the backbone of pharmaceutical development, manufacturing control strategies, and lifecycle management.Rather than a deep dive into requirements, this episode is designed to orient listeners to the full ICH landscape. It helps teams understand where different guidelines apply, who typically owns them, and how they collectively shape regulatory expectations. Future episodes in the series will explore individual Quality guidelines in detail.In this episode, you will learnWhat an ICH guideline is and how it differs from regulations and standardsWhy guidelines still matter during inspections and enforcementHow ICH organizes its guidance into Q, S, E, and M categoriesA high-level overview of the Quality Guidelines (Q1 through Q14), including:Stability (Q1)Analytical validation and development (Q2 and Q14)Impurities (Q3)Quality by Design and risk management (Q8 and Q9)Pharmaceutical Quality Systems and lifecycle management (Q10 through Q12)Continuous manufacturing (Q13)How different functional teams interact with different parts of the ICH frameworkThe next episode begins the deep dive into the Quality Guidelines, starting with ICH Q1 on Stability.Timestamps00:00 Introduction to the Series00:48 Overview of ICH Guidelines01:36 What an ICH Guideline Is and Is Not03:04 The Four ICH Guideline Categories04:08 Quality Guidelines Overview08:46 Safety Guidelines Overview09:28 Efficacy Guidelines Overview10:33 Multidisciplinary Guidelines Overview11:28 Wrap-Up and Next StepsSubhi 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.

🚀 Stay ahead in combination products, pharma, and medical devices 👉 https://www.letscombinate.com🎙️ Listen to more expert discussions on regulations, drug delivery, and quality 👉 https://www.letscombinate.com/Get expert insights on FDA regulations, risk management, quality systems, and the latest trends in drug-device combination products.In this end of year episode of Let’s Combinate: Drugs + Devices, host Subhi Saadeh reflects on the past year through the lens of Managing Oneself by Peter Drucker. Using the book’s core questions around strengths, values, learning style, performance, and contribution, Subhi shares how his thinking has evolved and how those ideas continue to shape his approach to work and learning.The episode explores the idea of learning by teaching and why podcasting has become an important way for Subhi to deepen his own understanding of complex topics. He also shares a brief life and professional update, including the launch of Let’s ComBinate BioWorks and a shift in focus toward work that bridges the drug and device worlds.The conversation closes with reflections on Drucker’s ideas about the second half of a career and introduces a new upcoming podcast series focused on ICH guidelines. Subhi outlines how the series will take a high level, practical approach to ICH, emphasizing how to read and engage with the guidance rather than treating it as a checklist.Episode Timeline00:00 Introduction and episode overview00:31 Introducing the upcoming ICH series01:36 Reflections on Managing Oneself03:27 Life and professional updates06:59 Thinking about the second half of a career08:19 Closing thoughtsSubhi 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.

In this short episode of Let’s Combinate: Drugs + Devices, Subhi Saadeh breaks down ICH Q13 and what “continuous manufacturing” actually means. He compares batch vs. continuous, explains how a batch still exists in continuous manufacturing, and covers the essentials quality teams care about: RTD/traceability, control strategy, and disturbances/diversion plus a quick high-level note on validation, release, and lifecycle.Timestamps00:00 Intro01:00 Batch vs. continuous (and batch definition)03:00 Modes of continuous manufacturing (ICH Q13 examples)04:30 RTD & traceability06:00 Control strategy07:30 Disturbances & diversion09:00 Validation / release / lifecycle (high level)10:00 Wrap-upSubhi Saadeh is the Founder and Principal of Let’s Combinate BioWorks and host of the Let’s Combinate: Drugs + Devices podcast/Youtube Channel. With experience across Quality, Manufacturing Commercialization, Sustaining and R&D, Subhi has helped industrialize and launch drug delivery systems for biologics, vaccines, and generics at leading organizations such as Pfizer, Gilead, and Baxter. Subhi focuses on bridging the disconnect between drug and device development and specializes in harmonizing internal systems, aligning internal and external partners, and helping combination product teams move from siloed execution to scalable, compliant, and patient-ready solutions. He currently chairs the Rx-360 Combination Product Working Group and was the International WG Chair at the Combination Product Coalition. He has contributed to global harmonization efforts through BIO, ASTM, and AAMI. He is a certified ISO13485 Lead Auditor, CQA and CQE.For questions, inquiries, or suggestions, please reach out at letscombinate.com or on the show’s LinkedIn Page.