What Are the Combination Product Types?

By Rhizome Team

Combination products represent a critical category of medical products that combine drugs, devices, and/or biological products. Understanding the different types of combination products is essential for manufacturers to ensure proper regulatory classification, comply with applicable requirements, and navigate the appropriate FDA review pathways.

The FDA's Office of Combination Products (OCP) categorizes combination products into distinct types based on how the constituent parts are physically, chemically, or otherwise combined. Each type has specific regulatory implications and requirements that manufacturers must address during development and submission.

Here we explore the officially recognized combination product types as defined by FDA regulations and guidance, providing clarity on how products are classified and what regulatory framework applies to each category.

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what are the combination product types

Answer

Combination products are medical products that combine two or more regulated components (drug, device, and/or biological product) into a single product or system. The U.S. Food and Drug Administration (FDA) defines several types of combination products based on their structure, packaging, and intended use. These categories help determine regulatory pathways, approval processes, and postmarket obligations. The main types of combination products include:

1. Single-Entity Combination Products

  • These products integrate two or more regulated components (drug, device, or biological product) into a single entity, either physically, chemically, or otherwise.
  • Examples:
    • Prefilled syringes (drug/device).
    • Drug-eluting stents (device/drug).
    • Transdermal patches that deliver drugs (device/drug).
    • Drug-coated mesh (device/drug).
  • Sources: 34917262728.

2. Co-Packaged Combination Products

  • These consist of two or more separate products packaged together in a single package or as a unit.
  • Examples:
    • Surgical kits containing a device (e.g., bandages) and a drug (e.g., antiseptic).
    • First-aid kits with multiple components (e.g., drugs and devices).
    • A vial of a drug packaged with a syringe for administration.
  • Sources: 35920262729.

3. Cross-Labeled Combination Products

  • These involve two or more separate products that are intended to be used together, where the labeling of one product references the other. Both products are required to achieve the intended therapeutic, diagnostic, or preventive effect.
  • Examples:
    • A light-emitting device intended for use with a specific light-activated drug.
    • A drug and a device that must be used together, such as a drug requiring a specific delivery device for administration.
  • Sources: 34589142427.

4. Investigational Cross-Labeled Combination Products

  • These are investigational products that are packaged separately but are intended for use together as described in their labeling or investigational plan.
  • Examples:
    • A drug and a device that are investigational and meant to be used together to achieve the desired therapeutic effect.
  • Sources: 39.

5. Drug-Led Combination Products

  • These are combination products where the primary mode of action (PMOA) is attributed to the drug component.
  • Examples:
    • A therapeutic drug product co-packaged with a vaginal applicator (device).
    • Drug-eluting implants.
  • Sources: 202728.

6. Device-Led Combination Products

  • These are combination products where the PMOA is attributed to the device component.
  • Examples:
    • Drug-coated stents.
    • Antimicrobial-coated catheters.
  • Sources: 202728.

7. Biologic-Led Combination Products

  • These products are led by the biologic component, with the drug or device playing a secondary role.
  • Examples:
    • Prefilled biologic delivery systems (e.g., syringes or patches for biologics).
    • Cellular therapy delivery systems.
  • Sources: 172128.

8. Drug-Device-Biologic Combination Products

  • These products combine all three components—drug, device, and biologic—into a single system.
  • Examples:
    • Complex therapeutic systems integrating a drug, a biologic, and a delivery device.
  • Sources: 1728.

9. Other Combination Product Configurations

  • This category includes products that do not fit neatly into the above classifications but still involve combinations of drugs, devices, and/or biological products.
  • Examples:
    • Convenience kits that include multiple components intended to be used together (e.g., drug vials co-packaged with devices).
    • Multiconstituent products (e.g., a vial containing powder for injection packaged with a reconstitution vehicle and syringes).
  • Sources: 1202229.

Regulatory Considerations

  • Combination products are regulated under 21 CFR 3.2(e), and their classification depends on how the components are combined or intended to be used together.
  • The Primary Mode of Action (PMOA) determines which FDA center (e.g., drugs, devices, biologics) has the lead for its regulation.
  • Manufacturers are encouraged to consult the FDA or the Office of Combination Products (OCP) for guidance on regulatory pathways and premarket submissions 41718232528.

This classification system highlights the diversity of combination products and their applications in addressing therapeutic, diagnostic, and preventive needs.