Drug Device Combination Products

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What is a Combination Product?

A combination product can be defined as a therapeutic or diagnostic product comprising drugs, medical devices, and biological products. A combination product usually has at least two components and sometimes all three. 

The conventional drug medical device combination products include – a syringe prefilled with a drug and co-packaged products such as a first-aid kit containing bandages and pain-relieving drugs.

Examples of Combination Products

The Code of Federal Regulations (CFR) classifies drug-device combinations into three categories: 

1. Single Entity

A single-entity combination product is a mixture of two or more components that creates one entity — for instance, drug and device, device and biologic, biologic and drug, or all three.

Here are some examples of single-entity combination products: 

  • Prefilled drug delivery devices: syringes, injector pens, insulin pumps, inhalers
  • Prefilled biologic delivery devices: syringes, nasal sprays
  • Medical devices merged with medications or biologics: patches and dressings for transdermal and antimicrobial purposes.
  • Drug/biologic combinations: antibodies combined with therapeutic drugs

2. Co-packaged

A co-packaged combination product is when multiple components are brought together and packaged as a single unit or package. These types of combination products are also known as convenience kits. 

There are various examples of co-packaging: 

  • Drug or vaccine vial packaged with a syringe
  • Liquid medication with dose-dispenser
  • The surgical tray containing surgical instruments and anesthetic drugs

3. Cross-labeled 

A cross-labeled combination product is a product that contains a device, drug, or biological product which are individually packaged. This product is intended to be used with a particular approved device, drug, or biological product, as stated in its investigation plan or suggested instructions. 

Both components must be combined to achieve the desired purpose, indication, or effect. Simply put, these products are sold separately but are meant to be used in combination with each other, as indicated on their labels.

Here are two examples of cross-labeling: 

  • Photosensitizing drug and activating laser or light source
  • Biological products activated by light, labeled for specific light source use.

Combinations Products Regulatory Requirements

The FDA established the Office of Combination Products in 2002 to classify medical products in the US and assign them to an FDA center for review and regulation based on their primary mode of action (PMOA). 

The PMOA is the most important therapeutic action of the combination product and determines the lead FDA investigation center. The primary mode of action also determines the type of regulatory submission needed.

Common regulatory pathways for combination products based on the principal mode of action (PMOA) include:

  • Submit a Premarket approval application (PMA), De Novo request, or 510(k) based on the PMOA for devices. 
  • Submit a New drug application (NDA) or abbreviated new drug application (ANDA) based on the PMOA for drugs.
  • Submit a Biologic license application (BLA) based on the PMOA for biologics.

The Outlook for Combination Products in Coming Years

Combination devices and drug products are becoming increasingly popular, providing precise treatment, better drug delivery, and increased effectiveness — global drug-device combinations market to exceed $177 billion by 2024.

These products simplify drug administration, reducing mistakes and improving patient adherence. Regulatory hurdles arise due to the involvement of diverse regulatory authorities. In response, the FDA established the Office of Combination Products in 2002 to tackle these challenges. 

As technology advances and the market grows, regulatory pathways and policies must adjust accordingly.

3iConcept Combination Products Proficiency

3i Concept specializes in providing consultancy services for medical device and drug-device combination products. We assist you in navigating through new product development and remediating Design History Files (DHF).

The 3i Concept team understands design history requirements for medical devices in the US, EU, and globally. We help your team comply with regulations, improve DHF practices, and address queries from agencies.

In addition to DHF content development and management, connect with us on [email protected] to understand more on DHF support services for medical device and drug device combination product (DDCP) which includes:

FDA Design Controls Requirements:

  • Quality System Regulation, 21 CFR Part 820
  • Design Control medical devices cGMP and 21 CFR 820.30
  • Device Master Records (DMR)
  • Device History Record (DHR)

EU MDR requirements:

  • The EU’s medical device regulations (EUMDR)
  • Technical File / Design Dossier for submission
  • QMS Compliance and Technical Documentation
  • GSPR (General Safety and Performance Requirements)

Risk Management (ISO 14971) for medical devices and drug device combination products including risk analysis, FMEAs, risk evaluation, and risk controls through corrective and preventive action (CAPA) plan and design control requirements.