Let's Combinate - Drugs + Devices with Subhi Saadeh

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.

Timestamps

00:00 Welcome and Guest Introduction

00:53 ICH Q2 vs MSA Mindset Shift

04:37 Surrogate Standards for Mechanical Testing

11:12 Platform Methods and ISO 11040

15:14 ISO vs USP Verification Debate

20:06 Outsourcing Analytical Testing Strategy

24:07 Choosing the Right Test Lab

26:20 Sponsor Oversight of Contract Labs

30:09 Wrap Up

About Jen Riter

Jen 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 Saadeh

Subhi 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.

Continuing the ICH Q series with ICH Q5. This episode explains why Q5 exists, how to read it, and what it means for combination products. Q5 addresses quality challenges unique to biologics made in living systems where products cannot be fully characterized by physical and chemical testing alone and show inherent variability. It harmonizes expectations for viral safety, cell substrate controls including master and working cell banks, stability, and comparability after manufacturing changes. For combination products, Q5 mainly applies to the biologic drug constituent through stability and change impact rather than device requirements.

00:00 Intro to ICH Q5

00:25 Meet the Host

00:32 Why Biologics Need Q5

00:56 Key Risks Explained

02:11 What Q5 Covers

02:40 Scope and Structure

03:19 Q5 A to E Breakdown

04:19 How to Read Q5

05:05 Q5 for Combination Products

05:59 Wrap Up and Next Episode

Subhi 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.

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.

Timestamps

00:00 Welcome and Guest Intro

00:53 The Hairiest CAPA Case

03:02 Human Error Root Cause

04:58 Common CAPA Misconceptions

06:11 Why Root Cause Fails

12:16 When to Open CAPA

17:26 CAPA Inputs and Triggers

19:28 One Process or Two

22:28 How to Investigate Properly

25:09 Tools for Root Cause

26:20 Problem Statement Basics

27:48 Wrap Up and Where to Find

Georg 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, Subhi Saadeh sits down with Elaine (Yi Ling Tan), Creator and Principal Consultant at MedTech Chopsticks, to break down China medical device market access and regulatory compliance under the NMPA.

The conversation explores why Western companies often underestimate China’s regulatory expectations — particularly when assuming EU or U.S. approvals, ISO standards, or FDA clearances will translate directly. Elaine explains how China requires demonstration of safety and effectiveness against applicable local standards primarily GB (national standards) and YY (medical device industry standards) including both mandatory and recommended variants (e.g., GB vs GB/T, YY vs YY/T).

The episode dives into China’s local type testing model and the role of Product Technical Requirements (PTRs) in defining test methods, parameters, accessories, and applicable standards for registration.

Elaine also outlines how China’s quality system expectations align to China Medical Device GMP rather than ISO 13485 including major GMP updates taking effect in November 2026 and discusses implications for foreign manufacturers.

Additional discussion topics include China agents and authorized representatives, clinical evaluation expectations, post-market reporting requirements, and how China’s device classification system can influence regulatory strategy.

⏱️ Timestamps

00:00 Welcome + Meet Elaine (MedTech Chopsticks)

00:38 Why China Is Different: Local Standards vs EU/US Assumptions

03:35 GB & YY Standards Explained (National vs Industry Standards)

05:07 Local Type Testing & PTRs: Building China Product Technical Requirements

06:52 China GMP Updates: Key Differences vs ISO 13485

12:42 China Agent vs EU Authorized Rep: Roles & Responsibilities

15:19 Choosing Local Test Labs: NMPA-Designated Testing Considerations

18:42 Planning Early: Standards Gaps, Clinical Evaluation & PMS Risks

24:43 China Certification & Device Classification Changes (Class I/II/III)

28:38 Where to Find Elaine + Closing

Subhi 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 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-guidelines

ICH Q4B Annex 3(R1) – Tests for Particulate Contamination (Subvisible Particles): https://database.ich.org/sites/default/files/Q4B%20Annex%203%28R1%29%20Guideline.pdf

Timestamps

00:00 Introduction to the ICHQ Series

00:03 What Pharmacopeial Harmonization Means

00:42 Why ICH Q4 Exists

01:55 ICH Q4 Framework and Structure

02:54 Understanding Q4A, Q4B, and the Annexes

03:59 Practical Examples (Particulates, Disintegration)

08:05 Conclusion and Next Steps

Subhi 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 breaks down ICH Q3, the family of guidelines that define how impurities are identified, evaluated, and controlled in drug substances and drug products.

Subhi explains what impurities are, why zero impurities is unrealistic in scalable manufacturing, and how ICH Q3 establishes a risk-based framework to protect patient safety and product quality. The episode walks through the structure of Q3A through Q3E, covering impurities formed during drug substance synthesis, degradation in drug products, residual solvents, elemental (metal) impurities, and extractables and leachables highlighting where drug delivery systems and combination products explicitly come into scope under Q3E.

This episode is a high-level, practical overview focused on how to read ICH Q3, how the sections fit together, and where the guideline applies and stops across the drug product lifecycle.

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Timestamps

00:00 Welcome to Let’s ComBinate

00:12 Introduction to ICH Q3

00:25 What Are Impurities and Why They Matter

00:51 Sources of Impurities and Risk-Based Control

02:11 Structure of ICH Q3 (Q3A–Q3E)

05:30 How to Read and Use ICH Q3

07:22 Q3E, Extractables & Leachables, and Drug Delivery Systems

09:21 Wrap-Up and Next Episode Preview

Subhi 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.

Timestamps

00:00 Introduction to Let’s ComBinate

00:42 Purpose and importance of ICH Q2

03:11 Scope and product coverage

06:10 Key validation characteristics

08:15 Practical application and reading ICH Q2

10:23 Conclusion and next steps

Subhi 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 and Devices, host Subhi Saadeh breaks down the 2025 draft update to the ICH Q1 guideline and explains what has actually changed and what has stayed the same.

ICH Q1 is the core stability guideline, and with the consolidation of multiple legacy guidelines into a single document, many readers have found the draft overwhelming. In this episode, Subhi steps back from line-by-line commentary and instead focuses on how to think about ICH Q1, how to read it efficiently, and how stability decisions are expected to be made.

The discussion covers why stability was one of the first topics harmonized by ICH, the fundamental stability concepts that still anchor the guideline, and how the revised structure emphasizes lifecycle management and data evaluation rather than introducing new science. Subhi also explains how ICH Q1 applies to drug-device combination products, including the role of the device as part of the container-closure system and why in-use stability often matters more than long-term storage.

This episode is part of an ongoing series walking through the ICH Q guidelines and is intended to help listeners navigate regulatory expectations with clarity and confidence.

Timestamps

00:00 Introduction

00:36 What ICH Q1 Is and Why It Exists

02:59 Core Stability Concepts in ICH Q1

04:51 What’s Changing in the 2025 Draft

05:35 How to Read ICH Q1

07:16 ICH Q1 and Drug-Device Combination Products

09:09 Closing and What’s Next

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 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 learn

What an ICH guideline is and how it differs from regulations and standards

Why guidelines still matter during inspections and enforcement

How ICH organizes its guidance into Q, S, E, and M categories

A 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 framework

The next episode begins the deep dive into the Quality Guidelines, starting with ICH Q1 on Stability.

Timestamps

00:00 Introduction to the Series

00:48 Overview of ICH Guidelines

01:36 What an ICH Guideline Is and Is Not

03:04 The Four ICH Guideline Categories

04:08 Quality Guidelines Overview

08:46 Safety Guidelines Overview

09:28 Efficacy Guidelines Overview

10:33 Multidisciplinary Guidelines Overview

11:28 Wrap-Up and Next Steps

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 Let’s Combinate: Drugs + Devices, Subhi Saadeh kicks off a new series focused on the International Council for Harmonisation (ICH) and its impact on drug and drug–device combination products.Subhi introduces what ICH is, why it was created, and how its guidelines shape global expectations for pharmaceutical quality, safety, efficacy, and lifecycle management. He walks through the historical challenges that existed before harmonization, explains how ICH guidelines are developed through the five-step process, and outlines why these standards matter—especially for teams working at the intersection of drugs and devices.The episode also sets the roadmap for the series, including upcoming deep dives into the ICH Quality guidelines (Q1–Q14) and how they apply in practice to combination products.00:00 Welcome to Let’s Combinate00:37 Why ICH Matters for Drug–Device Products02:22 What Is ICH?05:21 Evolution of ICH Guidelines10:18 The Five-Step ICH Guideline Process11:38 How This Series Will Work14:09 Wrap-Up and What’s NextSubhi Saadeh is a Quality Professional, Founder of Let's Combinate BioWorks 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.