Description
Section 3038 of the 21st Century Cures Act, enacted in December 2016 (P.L. 114-255) (“Cures Act”), substantially amended section 503(g) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 USC 353(g)), the principal section of the FD&C Act expressly addressing combination products. General themes of these amendments include enhancing clarity, predictability, efficiency, and consistency of premarket regulatory expectations for combination products, including by ensuring that Agency components and staff coordinate appropriately on premarket review of these products, and that Agency thinking is aligned in conducting these reviews. FDA is publishing this guidance as part of its efforts to implement Cures Act section 3038 and in keeping with the Agency’s long-standing commitment to transparency, efficiency, and regulatory consistency, to facilitate development of safe and effective combination products.
Scope & Applicability
Product Classes
9Products 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.
Example of a biologic-led combination product
Biological product that may be substituted for the reference product
Biological product highly similar to a reference product
Products licensed through BLA pathways under the PHS Act
Combination products where the drug is the primary constituent
Reference Listed Drug used as the basis for an ANDA submission.
Generally recommended for Enhanced Documentation; Regulatory classification mentioned for implantable sensors and HPV tests; Mentioned in the context of an in vitro nucleic acid test for CMV DNA.
Regulated under section 351(i) of the PHS Act; Virus, therapeutic serum, toxin, vaccine, or protein applicable to prevention or treatment; Alternative regulation category for products meeting device definition
Stakeholders
2Entity responsible for submitting applications under section 524B
Procedures for meetings of the committee
Regulatory Context
Attributes
5Primary Mode of Action determining the lead center
Regulatory standard for 510(k) clearance; demonstration required for 510(k) submission; regulatory standard for 510(k) clearance; Comparison of subject device parameters to predicate 510(k) submission numbers.
Determined by the sponsor for the investigational product.; investigational product(s) are stable over the period of use and only used within the current shelf life
assessing the therapeutic equivalence of a proposed generic drug-device combination product
proposed product must be bioequivalent to the RLD
Identified Hazards
Hazards
1Assessment of toxicity required in a 351(k) BLA
Related CFR Sections (4)
- 21CFR600.3§ 600.3 Definitions.
As used in this subchapter:Read full regulation →
- 21CFR314.3§ 314.3 Definitions.
(a) The definitions and interpretations contained in section 201 of the Federal Food, Drug, and Cosmetic Act apply to those terms when used in this part and part 320 of this chapter .Read full regulation →
- 21CFR814.20§ 814.20 Application.
(a) The applicant or an authorized representative shall sign the PMA. If the applicant does not reside or have a place of business within the United States, the PMA shall be countersigned by an authorized representative residing or maintaining a place of business in the United States and shall identRead full regulation →
- 21CFR814.44§ 814.44 Procedures for review of a PMA.
(a) FDA will begin substantive review of a PMA after the PMA is accepted for filing under § 814.42 . FDA may refer the PMA to a panel on its own initiative, and will do so upon request of an applicant, unless FDA determines that the application substantially duplicates information previously revieweRead full regulation →
Related Warning Letters (4)
- 2025-03-18
CGMP/Finished Pharmaceutical/Adulterated
Advanced Pharmaceutical Technology
- 2024-08-27
CGMP/Drugs/Adulterated
EyePoint Pharmaceuticals, Inc.
- 2024-08-06
CGMP/Finished Pharmaceuticals/Adulterated/Unapproved New Drug
Omega Tech Labs LLC
- 2021-06-29
Investigational Device Exemptions (IDE)/Premarket Approval Application (PMA)
Aquavit Pharmaceuticals, Inc
See Also (8)
- Questions and Answers on Biosimilar Development and the BPCI Act Guidance for Industry: Guidance for Industry (Status: Final)
- Sameness Evaluations in an ANDA — Active Ingredients (Status: Draft)
- Potency Assay Considerations for Monoclonal Antibodies and Other Therapeutic Proteins Targeting Viral Pathogens (Status: Draft)
- Nonclinical Safety Assessment of Oligonucleotide-Based Therapeutics (Status: Draft)
- Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related Considerations Guidance for Industry (Status: Final)
- Comparative Analyses and Related Comparative Use Human Factors Studies for a Drug-Device Combination Product Submitted in an ANDA: Draft Guidance for Industry (Status: Draft)
- Incorporation of Physical-Chemical Identifiers into Solid Oral Dosage Form Drug Products for Anticounterfeiting: Guidance for Industry (Status: Final)
- Nonclinical Safety Evaluation of Reformulated Drug Products and Products Intended for Administration by an Alternate Route (Status: Final)