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

✉️ subhi@letscombinate.com

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