Let's Combinate - Drugs + Devices

In 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.

Chapters
00:00 – Intro and ICH Q14 vs. Q2
01:08 – The Analytical Target Profile (ATP)
04:16 – The Analytical Procedure Lifecycle
05:32 – Risk-Based Development and Enhanced Approaches
06:20 – Where ICH Q2 Fits: Validation
08:04 – Connecting Q14 to ICH Q12 and Lifecycle Management
09:22 – Closing the ICH Quality Series

In 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 box

If 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.

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https://calendly.com/letscombinate/let-s-combinate-intro-session

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#ICHQ14 #ICHQ2 #ICHQ12 #AnalyticalValidation #PharmaQuality #QualityByDesign #LifecycleManagement #DrugDevelopment #CombinationProducts

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 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 subhi@letscombinate.com

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.