Description
This document provides guidance to industry and FDA staff on the underlying principles to determine the type of marketing submission that may be required for postapproval changes to a combination product, as defined in 21 CFR 3.2(e), that is approved under one marketing application, i.e., a biologics license application (BLA), a new drug application (NDA), or a device premarket approval application (PMA).
Scope & Applicability
Product Classes
4Products combining drug, device, or biological constituents; Generally recommended for Enhanced Documentation; Requires 14971-based framework incorporating ICH Q9; A drug-device combination where the device constituent part detects ingestion.
Products covered under application change guidance
Specific category of biological products
Subject of comparability guidance
Stakeholders
3Entity responsible for the approved NDA or ANDA; entity responsible for risk assessment
Persons submitting drug applications using designated AMTs
applicants should request a meeting with the intercenter review team
Regulatory Context
Attributes
2criteria for determining if a prior approval submission is required
Single mode of action expected to make the greatest contribution to therapeutic effects
Related CFR Sections (5)
- 21CFR3.2§ 3.2 Definitions.
For the purpose of this part:Read full regulation →
- 21CFR3.4§ 3.4 Designated agency component.
(a) To designate the agency component with primary jurisdiction for the premarket review and regulation of a combination product, the agency shall determine the primary mode of action of the product. Where the primary mode of action is that of:Read full regulation →
- 21CFR314.70§ 314.70 Supplements and other changes to an approved NDA.
(a) Changes to an approved NDA.Read full regulation →
- 21CFR601.12§ 601.12 Changes to an approved application.
(a) General.Read full regulation →
- 21CFR814.39§ 814.39 PMA supplements.
(a) After FDA's approval of a PMA, an applicant shall submit a PMA supplement for review and approval by FDA before making a change affecting the safety or effectiveness of the device for which the applicant has an approved PMA, unless the change is of a type for which FDA, under paragraph (e) of thRead full regulation →
Related Warning Letters (10)
- 2025-11-18
Nonprescription/OTC
Save Rite Medical
- 2025-11-18
Nonprescription/OTC
Medical Mega
- 2025-11-18
Nonprescription/OTC
Shoplet
- 2025-08-12
Unapproved New Drugs/Misbranded
Confer With
- 2024-07-30
Finished Pharmaceuticals/Unapproved New Drugs
ISIS.GOLD
- 2024-05-28
Finished Pharmaceuticals/Unapproved New Drug/Misbranded
Ward Smelling Salts
- 2024-03-26
Finished Pharmaceuticals/Unapproved New Drug/Misbranded
Ammonia Sport Inc.
- 2024-03-19
Finished Pharmaceuticals/Unapproved New Drug/Misbranded
Skull Smash LLC
- 2024-03-12
Unapproved New Drugs/Misbranded
Spirochaete Research Labs, LLC aka Scitus Laboratory Products
- 2024-03-05
Finished Pharmaceuticals/Unapproved New Drug/Misbranded
Innovative Formulations, LLC dba Insane Labz
See Also (8)
- Certain Ophthalmic Products: Policy Regarding Compliance With 21 CFR Part 4 Guidance for Industry: Guidance for Industry (Status: Final)
- Submission and Resolution of Formal Disputes Regarding the Timeliness of Premarket Review of a Combination Product: Guidance for Industry and FDA Staff (Status: Final)
- Early Development Considerations for Innovative Combination Products: Guidance for Industry and FDA Staff (Status: Final)
- Cellular Therapy for Cardiac Disease: Guidance for Industry (Status: Final)
- How to Write a Request for Designation (RFD): Guidance for Industry (Status: Final)
- User Fee Waivers, Reductions, and Refunds for Drug and Biological Products (Status: Final)
- Clinical Considerations for Therapeutic Cancer Vaccines: Guidance for Industry (Status: Final)
- The Content of Investigational Device Exemption (IDE) and Premarket Approval (PMA) Applications for Artificial Pancreas Device Systems: Guidance for Industry and Food and Drug Administration Staff (Status: Final)