Let's Combinate - Drugs + Devices with Subhi Saadeh

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 next: https://youtu.be/uG_Ea__-Pjc

Want a second set of eyes on your combination product quality system? Book a quick call: https://calendly.com/letscombinate/quick-chat

Sources

21 CFR Part 4 (eCFR): https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-4

FDA Guidance, CGMP Requirements for Combination Products: https://www.fda.gov/media/90425/download

Chapters

0:00 Intro

0:50 21 CFR Part 4 Subpart A vs. Subpart B

2:00 Full compliance vs. the streamlined approach

2:39 21 CFR 4.1: Scope (single-entity and co-packaged)

3:52 21 CFR 4.2 and 4.3: Definitions and which CGMPs apply

4:37 21 CFR 4.4: How to comply with CGMPs for combination products

5:38 Drug-based system: ISO 13485 and QMSR provisions to add

7:58 Device-based system: 21 CFR 211 provisions to add

11:24 Medical gas and 4.4(c)–(e): separate facilities

12:10 Wrap-up

About me

I'm Subhi Saadeh. I help companies make drug and device quality systems work together. I'm a consultant, auditor, and trainer focused on combination products, an ISO 13485 Lead Auditor, and an ASQ CQA and CQE. I've worked on prefilled syringes, autoinjectors, IV bags, cartridges, and vial-based systems, from clinical through commercial.

🌐 https://letscombinate.com

📅 https://calendly.com/letscombinate/quick-chat

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

✉️ [email protected]

#CombinationProducts #21CFRPart4 #QMSR

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 reading.

The episode also features an excerpt from Subhi’s conversation with Eric Pittman, a former FDA investigator who spent a decade as editor-in-chief of FDA’s Investigations Operations Manual.

IN THIS EPISODE

• What replaced QSIT and where to find it

• Why Part III is a useful starting point for industry

• How FDA reorganized inspection coverage into six QMS areas

• How product risks and risk management documentation help guide record selection

• What’s coming in the QMSR inspection readiness series

TIMESTAMPS

00:00 QSIT is gone: What changed with QMSR

00:50 The new FDA inspection program

01:39 The four-part inspection readiness series

02:47 Eric Pittman: Where industry should start

04:14 Will FDA publish a new QSIT guide?

05:06 Comparing the old and new inspection approaches

05:47 Four major subsystems to six QMS areas

06:57 Inspection models and record selection

07:37 Risk, controls, and inspection evidence

08:08 What’s next in the series

THE SERIES

1. QSIT to QMSR: Understanding the new inspection program

2. Inspection models, coverage, and record selection

3. The six QMS areas and how they connect

4. Inspection readiness: Preparing people, processes, and records, with lessons from early QMSR warning letters

RESOURCES

FDA Compliance Program 7382.850 — Inspection of Medical Device Manufacturers

Part III begins on page 20. Attachment A details the QMS areas, elements, and requirements.

https://www.fda.gov/media/80195/download

FDA Investigations Operations Manual — Chapter 5

https://www.fda.gov/media/166533/download

FDA QMSR Frequently Asked Questions

https://www.fda.gov/medical-devices/quality-management-system-regulation-qmsr/quality-management-system-regulation-frequently-asked-questions

ABOUT SUBHI SAADEH

Subhi Saadeh is the Founder and Principal of Let’s Combinate, a consultant, auditor, and trainer specializing in drug-device combination products, medical devices, and pharmaceutical quality systems. His experience spans quality, R&D, and commercialization, with a focus on design controls, supplier quality, inspection readiness, and translating regulatory expectations into practical execution.

Subhi is an ISO 13485 Lead Auditor and an ASQ Certified Quality Auditor and Certified Quality Engineer.

CONNECT WITH SUBHI

Consulting, audits, and training:

https://letscombinate.com

LinkedIn:

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

Schedule a quick chat:

https://calendly.com/letscombinate/quick-chat

Email:

[email protected]

FOLLOW LET’S COMBINATE

YouTube:

https://www.youtube.com/@LetsCombinate

Spotify:

https://open.spotify.com/show/71wYadhCrfLsdYTVachpD2

Apple Podcasts:

https://podcasts.apple.com/us/podcast/lets-combinate-drugs-devices/id1589285792

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 audit could be a desktop audit. People are a huge part of what makes an audit work.Full CQA Master Class:https://cqeacademy.teachable.com/p/the-cqa-master-class-courseChapters0:00 Intro1:39 Interviewing Fundamentals3:04 Conversational vs. Checklist3:49 Building Rapport4:29 Focus on the Process5:30 Open-Ended Questions5:58 Corroborating Information6:44 Group Interviews7:29 Using Translators8:20 Interview Challenges10:29 Time Management11:16 ClosingAbout SubhiSubhi Saadeh is the Founder and Principal of 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 pharma, biotech, medical devices, and combination products.Learn more about Let’s Combinate:https://letscombinate.com/Connect with Subhi on LinkedIn:https://www.linkedin.com/in/subhi-saadeh-1169aa21Need help?https://calendly.com/letscombinate/let-s-combinate-intro-session#Quality #Auditing #QualityAssurance #CQA #Pharma #MedicalDevices #CombinationProducts

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 moving forward would clearly violate requirements or SOPs

when schedule or business pressure is pushing a team to close something that isn’t actually closed

He also talks through some weaker reasons Quality says no, including:

personal preference or “this is how we’ve always done it”

uncertainty from lack of technical familiarity

applying more GMP rigor than the stage of development actually requires

If you work in quality, combination products, development, manufacturing, or technical leadership, this is a practical look at how to think about “no” in a more risk-based way.

Timestamps

00:00 Why Quality Says No

00:45 Channel Intro and Setup

02:02 No When Risk Is Real

03:06 No When Evidence Fails

05:02 No When Requirements Break

05:44 No to Schedule Pressure

07:48 Bad No From Preference

08:33 Bad No From Uncertainty

09:20 Overkill and Phase GMPs

10:08 Build Flexible Quality Culture

12:16 Wrap Up and Takeaways

Subhi Saadeh is a consultant, trainer, auditor, and the Founder and Principal of Let’s Combinate. He has spent his career across medical devices and pharmaceuticals, with experience spanning research and development, industrialization, quality systems, and combination products. Through Let’s Combinate, he helps professionals and organizations better understand and navigate the intersection of drugs, devices, quality, and regulatory requirements.

Connect with Subhi Saadeh

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

Website: http://letscombinate.com/

Book a quick chat: https://calendly.com/letscombinate/quick-chat

Email: [email protected]

Listen / Follow Let’s Combinate

YouTube: https://www.youtube.com/@LetsCombinate

Spotify: https://open.spotify.com/show/71wYadhCrfLsdYTVachpD2

Apple Podcasts: https://podcasts.apple.com/us/podcast/lets-combinate-drugs-devices/id1589285792

#Quality #CombinationProducts #Pharma #MedTech #RiskManagement #GMP #DesignControls #SupplierQuality #QualitySystems #LetsCombinate

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 BIMO inspections, the difference between inspections and investigations, the end of QSIT, and how companies can use FDA’s Investigations Operations Manual and compliance programs to prepare more effectively.

Timestamps

00:00 Introduction
00:48 FDA’s generalist and specialist inspection models
03:52 What is Bioresearch Monitoring (BIMO)?
05:03 What makes someone an effective FDA investigator?
08:39 Technical expertise versus auditing and inspection skills
11:25 What FDA investigators are actually looking for
14:07 Eric’s experience conducting 800–1,000 inspections
15:11 How investigators prepare, inspect, and write reports
19:44 Why FDA investigators sometimes “phone home”
23:35 The transition from ORA to OII
28:00 What responsibilities remain within OII?
30:31 FDA inspections versus investigations
33:05 The IOM, QSIT, and investigator discretion
38:25 How industry should use FDA compliance programs
44:13 What companies waste time preparing for
45:55 Where to find Eric

About Eric Pittman

Eric Pittman is Vice President of Quality Assurance and Regulatory Affairs at Project Farma. Before moving into industry, he spent more than 20 years at FDA across drugs, devices, foods, biologics, and bioresearch monitoring.

He served as Division Director for Bioresearch Monitoring West, was the U.S. delegate to the OECD Working Party on Good Laboratory Practice, and spent a decade as editor-in-chief of FDA’s Investigations Operations Manual. Eric is also an adjunct professor in Temple University’s QA/RA graduate program.

Connect with Eric

LinkedIn: https://www.linkedin.com/in/ericspittmanmba-fda
Project Farma: https://projectfarma.com

About Subhi Saadeh

Subhi Saadeh is a combination-product quality professional, consultant, and host of Let’s Combinate: Drugs + Devices. His work focuses on the intersection of pharmaceutical and medical-device requirements, including combination-product quality systems, design controls, supplier quality, manufacturing, inspection readiness, and regulatory strategy.

Through Let’s Combinate, Subhi brings together regulators, industry leaders, and technical experts to make complex drug-device topics easier to understand and apply.

Connect with Subhi

LinkedIn: https://www.linkedin.com/in/subhi-saadeh-1169aa21/
YouTube: https://www.youtube.com/@LetsCombinate
Website: https://letscombinate.com

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.

This is the first video in a series on acceptance sampling. Future videos will go deeper into attribute sampling, variable sampling, and how to select and apply sampling plans in practice.

Topics Covered:

* What acceptance sampling is

* Why acceptance sampling is probability-based

* AQL — Acceptance Quality Limit

* Why AQL does not simply mean “allowable percent defective”

* Attribute vs. variable acceptance sampling

* ISO 2859-1 / ANSI-ASQ Z1.4

* ISO 3951 / ANSI-ASQ Z1.9

* Operating Characteristic (OC) curves

* Producer risk vs. consumer risk

* How overly tight or overly loose sampling plans can create problems

Chapters

00:00 Introduction

01:30 Why Acceptance Sampling Matters

01:45 Perfect World vs. Reality

02:49 What Is Acceptance Sampling?

03:53 Attributes vs. Variables

05:21 What Is AQL?

07:05 Risk & the OC Curve

09:57 Producer & Consumer Risk

12:05 Practical Takeaway

About Subhi Saadeh

Subhi Saadeh is the Founder and Principal of Let’s Combinate, an independent media, education, and consulting company focused on drug device combination products, quality systems, and quality engineering.

Subhi is a consultant, trainer, and auditor with a background spanning R&D, industrialization, commercialization, and quality across the pharmaceutical and medical device industries.

He is also the host of Let’s Combinate: Drugs + Devices where he talks with industry leaders and breaks down complex quality, regulatory, device, pharma and combination-product topics.

**Need help with consulting, training, or auditing?**

Learn more at: [https://www.letscombinate.com](https://www.letscombinate.com)

**Connect with Subhi:**

LinkedIn: [https://www.linkedin.com/in/subhi-saadeh-1169aa21](https://www.linkedin.com/in/subhi-saadeh-1169aa21)

Email: [[email protected]](mailto:[email protected])

#AQL #AcceptanceSampling #QualityEngineering #Pharma #MedicalDevices #CombinationProducts #ISO2859 #ISO3951

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 unproven technologies, and how device companies can differentiate in an increasingly crowded market. Steven also discusses the growth of larger-volume subcutaneous delivery, the tradeoffs between reusable and disposable devices, sustainability, primary container strategy, and the changing role of sales and business development in drug delivery.

Subhi and Steven also dig into oral GLP-1s and whether oral drugs could ultimately displace injectables. Steven explains why route of administration alone does not determine the better solution — efficacy, patient adherence, cost, usability, and the overall treatment experience all matter.

The episode closes with Steven looking ahead to 2035 and explaining why he believes sustainability will be one of the major forces shaping the next generation of drug delivery devices.

Timestamps

00:00 Introduction and Steven’s Drug Delivery “Bookshelf”

02:24 From Marketing to Drug Delivery Strategy

06:10 What Makes a Device Commercially Successful in 2026?

11:11 Is the Large-Volume Injection Market Getting Crowded?

14:28 The Chicken-and-Egg Problem With New Device Technologies

19:25 CDAs, Proprietary Information and Working With New Suppliers

22:31 How Do You Sell a Drug Delivery Device in 2026?

29:17 Why Drug Delivery Is Still “Sexy”

31:20 Oral Drugs, Adherence and the Mucinex Horse Pill

33:18 Reusable Devices and Human Factors

35:22 Sustainability as a Drug Delivery Market Force

39:32 Cartridge vs. Prefilled Syringe

43:57 If You Had to Bet on One Drug Delivery Trend Through 2035

46:55 IV Drugs and the Shift Toward Subcutaneous Delivery

49:15 Steven’s Book Recommendation: Make Your Bed

51:22 Where to Find Steven

Steven Kaufman Bio

Steven Kaufman is the Founder of Combination Product Solutions, Inc. and a drug delivery and combination product executive with more than 21 years of industry experience.

His career has spanned device strategy, commercialization, business development, consulting, executive leadership, and entrepreneurship. Steven has held senior roles across the drug delivery industry and today works with device companies, biotech and pharmaceutical organizations, and investors on commercialization, technology strategy, platform evaluation, and bringing new drug delivery technologies to market.

Steven also serves as fractional Chief Commercial Officer at Portal Instruments.

Connect with Steven

Website: Combination Product Solutions

Email: [email protected]

LinkedIn: Steven Kaufman on LinkedIn

Subhi Saadeh Bio

Subhi Saadeh is a Quality Professional and host of Let’s Combinate. With a background in Quality, Manufacturing Operations, and R&D, he has worked in large medical device and pharmaceutical organizations supporting the development and launch of hardware devices, disposable devices, and combination products for vaccines, generics, and biologics.

For questions, inquiries, consulting, or episode suggestions:

Website: Let’s Combinate

LinkedIn: Subhi Saadeh on LinkedIn

Email: [email protected]

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 Subhi Saadeh

Subhi Saadeh is a combination product quality and compliance professional, consultant, auditor, trainer, and host of Let’s Combinate: Drugs + Devices, where he explores the intersection of pharmaceutical and medical device quality.

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 expectations around statistics, sampling, variability, and process capability, a move away from treating three validation batches as a default answer, and clearer discussion of traditional validation, continuous process verification (CPV), hybrid approaches, and ongoing process verification (OPV).

The goal isn't to suggest that all of these concepts are brand new. Many have been developing across the industry for years. What is interesting is seeing how PIC/S has now pulled them together into an updated recommendation that reflects current qualification and validation thinking.

Chapters

00:00 Big Update Overview

01:02 Who PIC/S Serves

01:28 Annex 15 Relationship

02:12 Scope and Exclusions

02:39 Why Update Now

04:05 Four Key Changes

04:47 Risk and Lifecycle Shift

06:43 Statistics and Sampling

07:48 Rethinking the Three-Batch Rule

08:30 Ongoing Process Verification

09:11 Traditional, CPV and Hybrid Approaches

10:45 Key Takeaways

About Subhi

Subhi Saadeh is a quality professional, consultant, auditor, and trainer who specializes in drug-device combination products, medical devices, pharmaceutical quality systems, supplier quality, and lifecycle management. Through Let’s Combinate, he helps pharmaceutical and medical device teams bridge the gap between drug and device quality, regulatory expectations, and practical execution.

Connect With Let’s Combinate

Website:
https://www.letscombinate.com

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

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

Apple Podcasts:
https://podcasts.apple.com/us/podcast/lets-combinate-drugs-devices/id1589285792

Spotify:
https://open.spotify.com/show/71wYadhCrfLsdYTVachpD2

Documents Discussed

PIC/S PI 006-4 — Recommendations on Qualification and Validation (2026)
https://picscheme.org/docview/11277

PIC/S PI 006-3 — Validation Master Plan, IQ/OQ, Non-Sterile Process Validation & Cleaning Validation (2007)
https://picscheme.org/docview/3447

EMA / PIC/S Concept Paper — Revision of Annex 15: Qualification and Validation (2026)
https://www.ema.europa.eu/en/documents/scientific-guideline/concept-paper-revision-guidelines-good-manufacturing-practice-medicinal-products-annex-15-qualification-validation_en.pdf

PIC/S Publications Page
https://picscheme.org/en/publications

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 mistake.

2) Look for patterns, not isolated errors: One typo is different from a recurring or systemic problem, unless the individual event is critical.

3) Scope the audit before you start: The objective, criteria, time, resources, and agenda need to align before the audit begins.

4) Technical expertise is not the same as audit skill: Auditing requires its own tools, tactics, strategies, interviewing skills, and qualification.

5) Lower the temperature to get better evidence: People communicate more clearly when the auditor reduces unnecessary anxiety, although assertiveness is sometimes necessary when information is being withheld.

Chapters

00:00 Audits Aren’t Gotchas

00:38 Audit the System, Not the Person

03:16 Look for Patterns, Not Isolated Mistakes

05:27 Set a Clear Audit Scope

08:21 Auditing Is Its Own Skill and Being Technical Helps

11:11 Lower the Temperature and Be a Human

About Subhi

Subhi Saadeh is a quality professional, consultant, auditor, and trainer who specializes in drug-device combination products, medical devices, pharmaceutical quality systems, supplier quality, and lifecycle management. Through Let’s Combinate, he helps pharmaceutical and medical-device teams bridge the gap between drug and device quality, regulatory expectations, and practical execution.

Learn more:

https://letscombinate.com/

[email protected]

Connect with Subhi on LinkedIn:

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