Let's Combinate - Drugs + Devices

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 Setup
00:14 Why ICH Q10 Matters
01:21 Lifecycle and Phase-Appropriate GMP
02:23 GMP Foundation and the PQS Model
02:58 Management Responsibility
03:31 Core PQS Elements
04:26 Enablers: Knowledge Management and QRM
04:40 Guideline Walkthrough: Sections 1 to 3
06:37 Continual Improvement of the PQS
07:45 Wrap Up and Next Episode

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, 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.

ICH 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 risk
Key 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 Q9
00:48 What is Risk in ICH Q9
01:44 Scope and Core Principles
03:21 Initiating QRM
05:09 Risk Assessment (Hazards, Likelihood, Severity)
07:27 Risk Control (Reduction and Acceptance)
08:46 Risk Communication and Review
10:04 ICH Q9 vs ISO 14971
11:51 Wrap Up

ICH Q9(R1) Final Guideline: https://database.ich.org/sites/default/files/ICH_Q9-R1_Guideline_Step4_2023_0118.pdf

ICH Q9 Briefing Pack: https://ich.org/page/q9r1-briefing-pack

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, 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=orlPpfQvb5k
QBD vs. Design Controls: https://www.youtube.com/watch?v=W_LSD0kKQ34

00:00 Introduction to ICH Q8
00:42 Related QbD Videos
01:12 Structure of ICH Q8
02:28 Objective and Scope
04:49 Annexes and QbD Concepts
05:20 Quality Target Product Profile
06:33 Critical Quality Attributes
07:09 Design Space and DoE
09:17 Control Strategy
10:06 Submission and Wrap-Up

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.

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.

In 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)

Timestamps

00:00 Intro
00:13 What Q7 Covers
01:23 Scope and GMP Start
02:19 API Starting Material
04:05 GMP Scaling (Table 1)
05:30 Quality and QMS
06:58 Production Controls
08:26 Validation
09:46 Change Control
10:27 CMOs / Supply Chain
12:11 Clinical
13:12 Takeaways

https://database.ich.org/sites/default/files/Q7%20Guideline.pdf

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, 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.

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

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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)

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Timestamps

00:00 Intro to ICH Q6
00:36 Host background
01:05 Why specifications matter
01:49 Q6A vs Q6B overview
02:33 Purpose of ICH Q6
02:59 What is a specification
04:27 Q6 R1 update themes
05:49 Lifecycle and risk based specifications
06:29 Wrap up and next steps

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.