Let's Combinate - Drugs + Devices

In 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 approval
How ICH Q12 supports more predictable lifecycle management
Reporting categories for post-approval CMC changes
Established Conditions versus supporting information
Examples of EC candidates, including CQAs, CPPs, material attributes, methods, sites, and process information
Why overcommitting or undercommitting ECs creates lifecycle risk
How PACMPs help companies plan future changes
What belongs in the PLCM document
How ICH Q12 applies to drug-device combination products
Why a strong PQS is essential for making Q12 work

Timestamps:
00:00 Introduction to ICH Q12
00:46 Why post-approval change gets difficult
02:45 Reporting categories
03:14 Established Conditions vs supporting information
04:10 EC examples: CQAs, CPPs, methods, sites, and process information
05:32 Post-Approval Change Management Protocols
06:38 PLCM document
08:08 Drug-device combination product callout
10:11 PQS and change management
10:28 Closing thoughts

Questions or feedback? Email [email protected]

Source 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.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 Pfizer, Gilead, and Baxter, supporting the development and launch of combination products across vaccines, biologics, and generics.

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.

Timestamps
00:00 ICH Q11 overview
00:47 Drug substance basics
01:14 Where Q11 fits in the ICH Quality framework
02:15 Section 3: Manufacturing process development
03:26 Linking drug substance quality to drug product quality
04:25 Section 5: Starting materials
05:41 Section 6: Control strategy
06:11 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 Pfizer, Gilead, and Baxter, supporting the development and launch of combination products across vaccines, biologics, and generics.

Six Major Auditing Strategies: Tracing, Process, Department, Element, Process-Based Management, and Discovery

Course Link: https://cqeacademy.teachable.com/p/the-cqa-master-class-course

In 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.

Timestamps
00:00 Six Audit Strategies Overview
00:22 Why Strategy Matters
01:13 Course Context and Setup
02:28 Tracing Method Explained
03:26 Process Approach Walkthrough
04:21 Department Method Deep Dive
05:26 Element Method Against Standards
06:12 Discovery Method String Pull
06:36 Pros, Cons, and Final Summary
09:53 Wrap Up and Next Session

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.

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.