Combination Products

1. A product comprised of two or more regulated components (i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic) that are physically, chemically, or otherwise combined or mixed and produced as a single entity [often referred to as a “single-entity” combination product];
2. Two or more separate products packaged together in a single package or as a unit and comprised of drug and device products, device and biological products, or biological and drug products [often referred to as a “co-packaged” combination product];
3. A drug, device, or biological product packaged separately that according to its investigational plan or proposed labeling is intended for use only with an approved individually specified drug, device, or biological product where both are required to achieve the intended use, indication, or effect and where, upon approval of the proposed product, the labeling of the approved product would need to be changed (e.g., to reflect a change in intended use, dosage form, strength, route of administration, or significant change in dose) [often referred to as a “cross-labeled” combination product]; or
4. Any investigational drug, device, or biological product packaged separately that according to its proposed labeling is for use only with another individually specified investigational drug, device, or biological product where both are required to achieve the intended use, indication, or effect [another type of “cross-labeled” combination product].

Combination Products can be classified under three categories: co-packaged (constituent parts packaged and sold together), single-entry (chemically or physically combined constituent parts), or cross-labeled (constituent parts sold separately).

Co-Packaged Products (21 CFR 3.2(e)2)

• Empty syringes packaged with a drug product
• Empty injection systems packaged with a drug product
• Transfer sets
• Surgical kits containing both a drug and a device to be used with it

Single-Entity Products (21 CFR 3.2(e)(1)

• Prefilled syringes
• Prefilled auto-injectors
• Metered-dose inhalers
• Dry powder inhalers
• Nasal-spray
• Prefilled pumps
• Transdermal patch systems
• Drug pills embedded with sensors
• Contact lens coated with a drug
• Condoms with spermicide
• Dental floss with fluoride
• Antimicrobial coated catheters/sutures

Separate Products With Cross-Labeling  (21 CFR 3.2(e)(3) or (e)(4)

• Light-activated drugs/biological products labeled for use with a specific light source device

1. The intended market – Whether the product is hitting the market in the United States of America (USA) or in the European Union (EU), each market has key differences.
2. The type of combination product – there are regulatory differences for each type of combination product previously mentioned: single-entity/integral products, co-packaged products, or cross-labeled products