DDCP
— Regulatory Pathway for —
DRUG-DEVICE COMBINATION PRODUCTS
UNDER THE EU LEGAL FRAMEWORK
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EU Drug-Device Combination Products: Process Map

The EU regulatory landscape for drug-device combination products is evolving rapidly. With the new variation regulation now in place and the anticipated variation categorisation guideline expected in Q2 2025, another crucial piece of the puzzle is falling into place.

At regenold GmbH, we've been at the forefront of these changes, guiding our clients through the complex approval journey for combination products. To illustrate the procedure from start to finish, we have created a DDC process map outlining four distinct steps:

  • Step 1: Pre-Evaluation
  • Step 2: Data Creation & Documentation
  • Step 3: NBOp & Approval
  • Step 4: Maintenance

Step 1: Pre-Evaluation

Defining the Right Regulatory Path: Classifying Your Drug-Device Combination Product

The first and most crucial step in the regulatory pathway is determining the correct classification of your product—whether it qualifies as an integral drug-device combination (iDDC), a co-packaged product, or both. Ideally, this decision should be made early in development and double-checked again for accuracy, as it defines the applicable regulatory route: either the EU Medical Device Regulation (MDR 2017/745) or Directive 2001/83/EC for medicinal products.

In the section that follows, we’ll explore key aspects of this classification, including:

  • Differentiating between iDDCs and co-packaged products
  • Verifying the need for a CE mark
  • Understanding the role of Notified Bodies (NBs) in the approval process

These foundational elements are essential for a smooth and compliant development pathway.

iDDC or Co-Packaged: Determining the Right Classification

The EU regulatory framework for drug-device combination products follows a hierarchical approach, making early classification essential for compliance. Below are key distinctions:

  • Integral Drug-Device Combinations (iDDC): These are single, combined products—such as pre-filled syringes—where the drug and device are physically integrated and not reusable. Governed primarily by Directive 2001/83/EC, the device component must meet relevant MDR safety and performance requirements.
  • Co-Packaged Products: These involve a drug and a device supplied together but as separate items (e.g., a vial of insulin with a reusable injection pen). Such products fall under both the medicinal product and medical device regulations.

Note:

  • Pure medical devices (e.g., empty syringes, wound dressings) are not covered here.
  • Medical devices with an ancillary medicinal substance (e.g., a heparin-coated catheter) are also outside the scope of this section, though they represent a core area of our expertise.

Borderline cases can present challenges. The MDCG 2022-5 guidance provides clarity by outlining criteria related to physical integration, exclusive use with a specific drug, and reusability.

To support your regulatory strategy, the following decision tree offers step-by-step guidance in identifying the correct classification and regulatory pathway for your combination product.

CE Mark and Notified Body Involvement: Key Steps in the Regulatory Assessment

Once the classification of your combination product is determined, the next step is verifying the regulatory status of the medical device component—particularly its CE marking and the involvement of a Notified Body (NB).

CE Mark Verification

Start by evaluating whether the device component already holds a valid CE mark under the Medical Device Regulation (MDR). It’s essential to ensure that its intended purpose aligns with the therapeutic or medical function of the combination product.

  • CE-marked and compatible: If alignment is confirmed, proceed confidently to the next step in the regulatory pathway.
  • No CE mark or not compatible:
    - For co-packaged products, identify a suitable alternative that meets MDR requirements.
    - For iDDCs, classify the device component per MDR Annex VIII rules as it would be a standalone medical device.

Notified Body (NB) Involvement

The need for NB involvement depends on the device classification, which is determined based on factors such as the intended use, invasiveness, duration of contact, and the potential risk to users or patients—defined in detail in MDR Annex VIII.

  • Class I devices (e.g., non-sterile syringes without measurement markings) typically do not require NB review.
  • Higher-risk classes (Is, Im, IIa, IIb, III)—including sterile prefilled syringes or syringes with graduation—do require the involvement of a Notified Body seeking for Notified Body opinion (NBOp).

Understanding and fulfilling these requirements early in development ensures smoother regulatory progress and helps avoid costly delays.

Key Considerations for EU Regulatory Compliance of Drug-Device Combination Products

Successfully navigating the EU regulatory pathway for drug-device combination products requires a clear understanding of classification rules, applicable legislation, and the involvement of regulatory bodies.

Integrated vs. Co-Packaged: Choosing the Right Framework

  • Integral Drug-Device Combinations (iDDCs) require a single marketing authorization under medicinal product legislation (Directive 2001/83/EC). However, the device component must comply to the applicable general safety & performance requirements (GSPRs) of Annex I MDR 2017/745.
  • Co-packaged products, where the drug and device are supplied together but not physically integrated, are subject to dual regulatory frameworks, applying both medicinal and medical device requirements.

Device Classification: Why It Matters

The classification of the device component is critical and depends on:

  • Intended use
  • Sterility
  • Functional features (e.g., presence of graduation markings)

For example, a prefilled syringe containing a medicinal product is considered an iDDC and regulated primarily as a medicinal product. However, its device component (the syringe) must still comply with MDR. If it is sterile or includes graduations, Notified Body (NB) involvement is mandatory.

This structured approach—guided by key EU documents—ensures regulatory compliance while providing clarity on product classification and oversight.

Essential References:

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