Let's Combinate - Drugs + Devices with Subhi Saadeh

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.

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.

Subhi Saadeh interviews Lucas Pianegonda, founder of Grad and a plastics expert in medical technology, on how medtech companies actually choose materials—and where it goes wrong. Many teams default to “we’ve always used this” or rely on a molder’s preferred grade, but those shortcuts can drive cost, delay timelines, and create downstream regulatory risk.

Lucas breaks down a more structured, data-driven approach to material selection that balances performance, processability, regulatory compliance, cost, and sustainability. They cover how early material decisions impact total cost of goods, why late changes lead to retooling and delays, and how to think holistically across the device lifecycle.

The conversation also explores common processing methods like injection molding and extrusion, key polymer categories, and emerging regulatory risks tied to additives, PFAS, and legacy materials. Subhi and Lucas discuss how GRAS and California Prop 65 are often misunderstood in medtech, and why biocompatibility is a device-level risk assessment, not a material checkbox grounded in screening, chemical characterization, and toxicological evaluation.

⏱️ Timestamps

00:00 Welcome and Guest Intro

00:43 Why Materials Drive Cost

02:17 Common Selection Pitfalls

03:35 Data-Driven Framework

06:10 Early Choices Prevent Rework

09:17 Processing Methods Overview

10:23 Polymer Categories Explained

12:58 Regulatory Risks and PFAS

19:26 GRAS and Prop 65 Basics

23:21 Biocompatibility Early Screening

28:55 ISO 10993 Updates

30:36 What Toxicologists Do

33:41 Where to Find Lucas

34:07 Closing

Lucas Pianegonda Website: https://www.gradical.ch/

Lucas on LinkedIn: https://www.linkedin.com/in/lucas-r-pianegonda-81142b110/

Lucas on YouTube: https://www.youtube.com/channel/UChPQB4eXQz3c_U2zZXAmEuQ

ISO 10993 Overview: https://www.iso.org/standard/68936.html

California Prop 65: https://www.p65warnings.ca.gov/

GRAS Overview (FDA): https://www.fda.gov/food/generally-recognized-safe-gras

Lucas Pianegonda is a medical technology plastics expert and founder of Gradical, where he helps medtech companies make smarter material selection decisions. He specializes in a holistic approach that connects performance, manufacturability, regulatory risk, cost, and sustainability to prevent costly redesigns and delays later in development.

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.

This is a lesson out of my ASQ CQA course with Andy Robertson, on how to write and classify audit findings.

Access the full CQA course here: https://cqeacademy.teachable.com/p/the-cqa-master-class-course

I break down key terms like finding, nonconformity, observation, and noncompliance, and explains that everything must tie back to requirements and objective evidence. The episode covers when to write a nonconformity vs an observation, common severity levels (critical, major, minor), and how to structure clear findings. I also cover how to sequence audit results and where auditors often go wrong, especially when they insert opinion or recommend solutions.

Timestamps

00:00 Course preview

00:42 Key audit terms

01:56 What makes findings reportable

04:16 Severity classification

06:42 Writing findings

07:57 Structuring reports

10:38 Auditor boundaries

Subhi Saadeh is a certified ISO 13485 Lead Auditor, CQE, and CQA with experience leading audits and building quality systems across medical devices and combination products at companies like Baxter, Pfizer, and Gilead Sciences. Through Let’s ComBinate, he focuses on bridging the gap between pharma and devices through educational content, industry collaboration, and consulting.

In this episode of Let’s ComBinate, Subhi Saadeh sits down with Joseph Luminiello, CEO and Co-Founder of RCG Intel, to break down how competitive intelligence is actually used in biopharma and why most companies get it wrong.

Joe introduces a practical framework built on three pillars: data (scientific publications and congresses), signal intelligence (press releases and filings), and human intelligence, which provides the context needed to interpret what those signals actually mean. While data and AI tools are becoming more accessible, Joe explains why interpretation and real-world insight remain the true differentiators in strategic decision-making.

The conversation covers real-world applications across pharma strategy, including evaluating low-cost API suppliers, make-versus-buy decisions, competitor assessments, and forecasting. Subhi and Joe also discuss how cultural incentives and assumptions often shape forecasts more than data, and why even well-built models can miss significantly.

Timestamps

00:00 Introduction

00:51 What is competitive intelligence

02:57 Human intelligence in practice

05:37 How insights are sourced

07:59 Validating and triangulating data

12:37 Forecasting and key assumptions

18:01 Common client blind spots

20:31 Speed of change in pharma

23:56 Why context matters more than raw data

27:27 Tools, congress strategy, and wrap-up

Links

RCG Intel:

https://rcgintel.com/

Joseph Luminiello on LinkedIn:

https://www.linkedin.com/in/joeluminiello/

Joseph Luminiello is the CEO and Co-Founder of RCG Intel, a boutique competitive intelligence consultancy serving the pharmaceutical and biotech sector. With more than 40 years of experience across healthcare, biopharma, and strategic intelligence, Joe has built his career around what he calls prescience, the ability to synthesize disparate data points and anticipate how they will shape the future. Before launching RCG Intel, Joe served as CEO of multiple biopharma companies, including AVM Biotechnology and Third Coast Therapeutics, where he raised capital and advanced drug development programs. As Founder and CEO of SmartHealth Catalyzer, he built a 150-member senior executive operations team and sourced over 130 intellectual property projects from Midwest universities. Earlier in his career, he spent six years at Takeda Pharmaceuticals, where he rose to Vice President of Business Development, contributed to diligence for Takeda’s acquisition of Nycomed, and helped launch Takeda Canada as its second employee.

Subhi Saadeh is the Founder and Principal at Let’s ComBinate BioWorks. He is a Certified Quality Auditor and ISO 13485 Certified Lead Auditor with leadership experience at Baxter, Pfizer, and Gilead Sciences. Subhi has extensive experience across drug-device combination products, including supplier quality, development quality, design controls, purchasing controls, audits, and management of contract manufacturers and external partners. Through Let’s Combinate, he is focused on bridging the gap between pharma and devices by creating educational content, participating in industry groups, and providing consulting support to align development, quality, and regulatory expectations.