Let's Combinate - Pharma + Medical Devices with Subhi Saadeh

Career growth in pharma and medical devices takes technical knowledge, leadership, and the ability to earn your team’s trust. In this episode, Subhi Saadeh shares a lesson from leading a drug-device combination product program that changed how he approached his career in quality.

Early in my career, I was excited about getting on big projects, gaining exposure, and proving what I could do. But leading a team with deeper technical expertise than I had taught me something I had to learn the hard way: it’s not about you.

I...

Combination product quality with Ben Locwin: why drug and device quality systems differ, how human factors studies are designed, what to do when a CDMO's clean audit doesn't match its performance, and how ISO 14971 risk management compares with ICH Q9.

This conversation was recorded for Ben Locwin's Life Science Shifts podcast from Reliant Life Sciences, with Subhi Saadeh as the guest. It covers where pharma and medical device thinking diverge, and what that means when one product has to satisfy both.

IN THIS EPISODE

- Why drugs and devices prove safety and effectiveness...

21 CFR Part 4 sets the CGMP requirements for combination products. If your product has a drug and a device in it, you're on the hook for both sets of regulations. In this video, I walk through Part 4 Subpart A section by section: the scope, the key definitions, which CGMPs apply, and the two ways to comply, including the streamlined approach under 4.4(b).

Updated for February 2026, when the device side moved to the QMSR and ISO 13485, plus the new medical gas provisions.

Working on your first combination product program? Watch this...

QMSR became effective on February 2, 2026. Alongside that change, FDA retired the Quality System Inspection Technique (QSIT) and began using the inspection process described in Compliance Program 7382.850.

What does that mean for industry and how should we use the new program to prepare?

In this episode of Let’s Combinate: Drugs + Devices, Subhi Saadeh introduces a four-part series on QMSR inspection readiness. We compare QSIT’s four major inspection subsystems with the new program’s six QMS areas, explore how risk informs inspection coverage, and identify where industry should start readin...

A huge part of the job is knowing how to interview people, understand how work is actually performed, and corroborate what you hear against records, observations, and other objective evidence.In this episode, I pulled one of the lessons from the auditing course Andy Robertson and I developed and walk through some of the fundamentals of audit interviewing: building rapport, asking open-ended questions, avoiding overly checklist-driven interviews, corroborating information, managing group interviews and translators, and handling some of the situations that make interviews difficult.If documents and records alone were enough to understand the quality of an organization, every...

Quality has a reputation for saying no.

Sometimes that’s exactly the right call. Other times, “no” is just the easiest answer.

In this episode, Subhi breaks down four situations where Quality should absolutely stop the train, and a few where it’s worth stepping back and asking what’s really driving the no in the first place.

Subhi covers:

when there is real patient or product risk

when the evidence doesn’t support the decision

when movin...

FDA is changing how it organizes and deploys its investigators but it isn’t simply returning to the old generalist model.

Eric Pittman spent more than 20 years at FDA, conducted approximately 800+ inspections, led the Bioresearch Monitoring Division West, and served for a decade as editor-in-chief of FDA’s Investigations Operations Manual.

In this episode, Eric explains how FDA investigators are trained to think, the difference between technical expertise and inspection skill, why investigators sometimes “phone home,” and what the transition from ORA to OII means for the agency’s inspection model.

We also discuss BI...

Acceptance sampling is one of the most commonly used and commonly misunderstood tools in quality.

In this video, I break down the fundamentals of acceptance sampling: what it is, what an AQL actually means, the difference between sampling by attributes and variables, and the risk involved when we use a sample to make an accept/reject decision about an entire lot.

We’ll also introduce Operating Characteristic (OC) curves, producer risk, and consumer risk — because acceptance sampling is probability-based and every sampling plan comes with tradeoffs.

In this episode, Subhi Saadeh sits down with Steven Kaufman, Founder of Combination Product Solutions, Inc. and fractional Chief Commercial Officer at Portal Instruments, to discuss where the drug delivery device market is headed and what it takes for new technologies to actually make it to patients.

Steven brings more than 21 years of experience across drug delivery and combination products, spanning strategy, business development, commercialization, consulting, and executive leadership.

The conversation explores what makes a drug delivery device commercially successful in 2026, why pharma companies can be hesitant to adopt...

After 250 straight weeks of publishing Let’s Combinate every Wednesday, I’m making a change.

Starting now, new episodes will go live Mondays at 5:00 AM CT.

To everyone who watches, listens, shares, or has been part of the journey: thank you. This podcast has been one of the most enriching things I’ve ever done.

See you Monday.

🌐 https://letscombinate.com

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

💼 https://www.linkedin.com/in/subhi-saadeh-1169aa21

About...

PIC/S has issued its first major update to its qualification and validation recommendations in nearly 20 years. PI 006-4 replaces PI 006-3 from 2007 and brings the document much closer to how qualification and validation are approached today.

In this video, I walk through where PI 006-4 fits within the broader GMP framework, how it relates to EU Annex 15, and the sections I think are most worth paying attention to.

A few of the major themes include a much stronger emphasis on quality risk management and lifecycle thinking, more explicit...

Audits are not supposed to be gotchas, and they are not meant to evaluate one person’s work in isolation. A good audit looks at whether a system is suitable, effective, and adequate and where it may need to improve.

In this video, I share the lessons I learned as I moved from being audited and supporting audit rooms to conducting audits as a certified lead auditor:

1) Audit the system, not the person: The goal is to understand how the system operates, not to catch an individual making a mi...

What is a Quality Unit and how do Quality Assurance and Quality Control fit within it?

In this episode, I explain the practical differences between the Quality Unit, QA, and QC across pharmaceutical, medical-device, and combination-product companies. We’ll look at the Quality Unit’s major responsibilities, why QA is generally system- and process-focused, why QC is generally testing- and product-focused, and why the organizational structure varies between companies.

CHAPTERS

00:00 What is a Quality Unit?

01:18 The Quality Unit as the umbrella function

Quality is often treated like a necessary function rather than an exciting career path. But working in quality can give professionals in pharma, biotech, and MedTech a much broader understanding of how regulated businesses actually operate.

In this video, Subhi Saadeh explains three reasons everyone in the industry should consider spending time in quality:

You learn how the business works. Quality follows the product across its lifecycle from development and suppliers through manufacturing, operations, regulatory changes, and post-market activities.

You develop judgment. Quality professionals regularly make structured...

Most discussions about One QMS focus on harmonization.

But before deciding whether a single global Quality Management System is the right approach, it's worth understanding the three primary ways organizations structure a QMS.

In this episode, I compare centralized, decentralized, and federated (hybrid) Quality Management System models, including the trade-offs of each in terms of ownership, standardization, flexibility, governance, and decision-making.

We also walk through how the document hierarchy typically differs across each model—from the Quality Policy and Quality Manual to standards, SOPs, wo...

In this episode of Let’s Combinate: Drugs + Devices, Subhi Saadeh talks with Julia Anthony, founder and chief strategy officer of Solution Medical, about adrenal crisis, emergency hydrocortisone, and what it takes to build a drug-device combination product from a patient need.

Julia was born with salt-wasting congenital adrenal hyperplasia, a life-threatening form of adrenal insufficiency. Because her body cannot make cortisol, she takes cortisol replacement daily and may need an emergency hydrocortisone injection during a crisis.

The problem?

The current emergency injection can ta...

Download the free Drug vs. Device Quality comparison guide here: https://letscombinate.kit.com/216fbfc6c2

In this Let’s Combinate episode, Subhi explains why drug and device quality are not the same and highlights five key areas where they differ for combination products.

Drug quality often focuses on consistently remaking the product that was proven clinically, using critical quality attributes, specifications, analytical methods, stability, process validation, and batch release.

Device quality emphasizes design robustness and intended use through design controls and product realization, fr...

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

Finished medical devices can create a lot of surprises when they are added to combination product kits.

A needle, vial adapter, filter, or transfer device may already be sterile, cleared, qualified, and sold at massive scale.

But already on the market does not automatically mean ready for your combination product.

In this episode, I talk through the challenges of selecting finished medical devices for combination product kits and the three lifecycle...

One of the hardest parts of auditing is not knowing what to look for.It is deciding where to start. Do you trace a deviation? Walk the process? Focus on one department? Audit CAPA across the organization? Or pull on a thread that does not quite make sense?

In this video, Subhi walks through six audit strategies from the ASQ Certified Quality Auditor Body of Knowledge and explains how they apply in real-world pharma, biotech, and combination product audits.

The six strategies covered are:

1. Tracing

2...

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...

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...

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...

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.

...

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...

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...

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 (p...

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 su...

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)

Ti...

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 toget...

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...

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...

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 st...

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...

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...

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...

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 G...

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...

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 le...

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 IC...

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 di...