Podcast
Let's Combinate - Drugs + Devices
Hosted by Subhi Saadeh · EN
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!
34episodes
Episodes
Newest firstAll episodes
241 - ICH Q14 Explained: Have We Been Validating Methods Backwards?
1w ago00:10:29Tap to summarizeIn this final episode of the ICH Quality series, we walk through the most important concepts in ICH Q14 and how they fit into the broader ICH quality framework.Rather than reviewing the guideline section by section, this episode focuses on the ideas that are most useful in practice: Why does ICH Q14 start with the Analytical Target Profile (ATP)? How is it different from ICH Q2? How do you develop analytical procedures using a science- and risk-based approach? And what does all of this have to do with ICH Q12 and lifecycle management?One quick note: at the time of recording, ICH Q14 remains under public comment, so some details may evolve before the final version is adopted.Chapters00:00 – Intro and ICH Q14 vs. Q201:08 – The Analytical Target Profile (ATP)04:16 – The Analytical Procedure Lifecycle05:32 – Risk-Based Development and Enhanced Approaches06:20 – Where ICH Q2 Fits: Validation08:04 – Connecting Q14 to ICH Q12 and Lifecycle Management09:22 – Closing the ICH Quality SeriesIn this episode, we cover:• Why ICH Q14 exists• The difference between ICH Q14 and ICH Q2• What an Analytical Target Profile (ATP) is• ATP examples and performance criteria• Technology selection and fit-for-purpose methods• The analytical procedure lifecycle• Risk assessments and enhanced development approaches• Multivariate experiments and DOE concepts• Analytical procedure control strategies• Validation and the role of ICH Q2• Lifecycle management of analytical procedures• The connection between ICH Q14 and ICH Q12• Why understanding matters more than simply checking a boxIf you've followed along through the ICH Quality series, one of the themes that keeps showing up is that quality isn't something you test into products at the end. Whether we're talking about Q8, Q9, Q10, Q12, or now Q14, the emphasis continues to shift toward building knowledge, understanding risk, and using that understanding throughout the lifecycle.Subhi 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, speaker, and host of the Let's Combinate podcast, with experience across companies including Pfizer, Gilead, and Baxter supporting vaccines, biologics, generics, and combination products.📅 Schedule an intro session:https://calendly.com/letscombinate/let-s-combinate-intro-session🎙️ Let's Combinate Podcast:https://www.letscombinate.com#ICHQ14 #ICHQ2 #ICHQ12 #AnalyticalValidation #PharmaQuality #QualityByDesign #LifecycleManagement #DrugDevelopment #CombinationProducts
Transcribe →240 - ICH Q13: Continuous Manufacturing, Batches, Residence Time Distribution and Control Strategy
2w ago00:11:08Tap to summarizeICH 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.
Transcribe →239 - ICH Q12: What’s Binding? Established Conditions and Post-Approval Changes
3w ago00:10:45Tap to summarizeIn this episode, Subhi breaks down ICH Q12, the guideline focused on post-approval change management and pharmaceutical product lifecycle management.The core question behind ICH Q12 is simple: once a product is approved, what is actually binding, what is supporting information, and how should future changes be managed?This episode covers the major Q12 concepts, including reporting categories, Established Conditions, supporting information, Post-Approval Change Management Protocols, the Product Lifecycle Management document, and the role of the Pharmaceutical Quality System.Subhi also discusses why Q12 matters for drug-device combination products, where lifecycle changes may involve CMC information, device constituent parts, functional performance characteristics, and the broader control strategy.Key topics covered:Why post-approval change can become difficult after approvalHow ICH Q12 supports more predictable lifecycle managementReporting categories for post-approval CMC changesEstablished Conditions versus supporting informationExamples of EC candidates, including CQAs, CPPs, material attributes, methods, sites, and process informationWhy overcommitting or undercommitting ECs creates lifecycle riskHow PACMPs help companies plan future changesWhat belongs in the PLCM documentHow ICH Q12 applies to drug-device combination productsWhy a strong PQS is essential for making Q12 workTimestamps:00:00 Introduction to ICH Q1200:46 Why post-approval change gets difficult02:45 Reporting categories03:14 Established Conditions vs supporting information04:10 EC examples: CQAs, CPPs, methods, sites, and process information05:32 Post-Approval Change Management Protocols06:38 PLCM document08:08 Drug-device combination product callout10:11 PQS and change management10:28 Closing thoughtsQuestions or feedback? Email subhi@letscombinate.comSource referenced in this episode: ICH Q12, Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management, Final version adopted 20 November 2019. Screenshots shown in this video are from the ICH Q12 guideline and are included for educational commentary. https://database.ich.org/sites/default/files/Q12_Guideline_Step4_2019_1119.pdfSubhi 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.
Transcribe →239 - ICH Q11 in 6 Minutes
May 2000:06:06Tap to summarizeIn 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.
Transcribe →238 - 6 Audit Strategies Every Auditor Should Know
May 1300:10:04Tap to summarizeSix Major Auditing Strategies: Tracing, Process, Department, Element, Process-Based Management, and DiscoveryCourse Link: https://cqeacademy.teachable.com/p/the-cqa-master-class-courseIn this episode, Subhi explains why selecting the right auditing strategy matters when auditors have limited time, limited access, and a specific audit objective. He walks through six major strategies: tracing, process approach, process-based management, department method, element method, and discovery method.The episode covers how each strategy works, where it is useful, and where it can fall short. Subhi also explains why real audits rarely rely on only one method. Strong auditors know how to combine strategies based on the audit objective, the evidence being reviewed, and what the audit trail reveals.Timestamps00:00 Six Audit Strategies Overview00:22 Why Strategy Matters01:13 Course Context and Setup02:28 Tracing Method Explained03:26 Process Approach Walkthrough04:21 Department Method Deep Dive05:26 Element Method Against Standards06:12 Discovery Method String Pull06:36 Pros, Cons, and Final Summary09:53 Wrap Up and Next SessionSubhi 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.
Transcribe →237 - ICH Q10: The Pharmaceutical Quality System
May 600:08:12Tap to summarizehis 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.
Transcribe →236: ICH Q9: Quality Risk Management (QRM) + ISO 14971 Differences
Apr 2900:12:16Tap to summarizeICH Q9 is one of the most referenced guidelines in pharma and one of the most misunderstood.In this video, I break down what Quality Risk Management (QRM) actually is, how the process works, and how it’s different from ISO 14971.We cover:What “risk” means in ICH Q9 (probability × severity)The full QRM process (initiation → assessment → control → communication → review)How to actually think through risk (not just document it)Why supply disruption is a patient riskKey differences vs ISO 14971 (planning, traceability, verification)If you work in pharma, devices, or combination products, this is foundational.TIMESTAMPS 00:00 Welcome to ICH Q900:48 What is Risk in ICH Q901:44 Scope and Core Principles03:21 Initiating QRM05:09 Risk Assessment (Hazards, Likelihood, Severity)07:27 Risk Control (Reduction and Acceptance)08:46 Risk Communication and Review10:04 ICH Q9 vs ISO 1497111:51 Wrap UpICH Q9(R1) Final Guideline: https://database.ich.org/sites/default/files/ICH_Q9-R1_Guideline_Step4_2023_0118.pdfICH Q9 Briefing Pack: https://ich.org/page/q9r1-briefing-packSubhi 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.
Transcribe →235 - ICH Q8: How Pharmaceutical Development Actually Works
Apr 2200:10:49Tap to summarizeThis 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.
Transcribe →234 - ICH Q7: The GMP Framework for API Manufacturing
Apr 1500:13:55Tap to summarizeIn this episode of Let’s Combinate, Subhi breaks down ICH Q7. Unlike topic-specific guidelines, Q7 covers the full GMP framework for API manufacturing. This episode walks through how to actually read it and what matters in practice.Covers: • Scope and where GMP begins • API starting material (core concept) • GMP scaling across the process (Table 1) • Quality unit and QMS expectations • Production and in-process controls • Validation and change control • CMOs and supply chain • Clinical trial flexibility (Section 19)Timestamps00:00 Intro00:13 What Q7 Covers01:23 Scope and GMP Start02:19 API Starting Material04:05 GMP Scaling (Table 1)05:30 Quality and QMS06:58 Production Controls08:26 Validation09:46 Change Control10:27 CMOs / Supply Chain12:11 Clinical13:12 Takeawayshttps://database.ich.org/sites/default/files/Q7%20Guideline.pdfSubhi 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.
Transcribe →233 - Most Teams Misunderstand Specifications | ICH Q6
Apr 800:06:57Tap to summarizeICH 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.
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