Article 117 Consultation Procedure: EMA Opinion for Drug-Device Combinations

You're reviewing a submission timeline for a drug-eluting stent. Someone asks: "Do we need EMA consultation before the Notified Body can issue the CE certificate?"

You pause. The device incorporates a medicinal substance where the action is ancillary to the device—but you're not sure whether that means you need to consult EMA first, or whether the Notified Body handles it independently.

Get this wrong, and your timeline extends by months. Get it right, and you can plan your pre-submission activities with confidence.

What Is the Article 117 Consultation?

Article 117 of the Medical Devices Regulation (EU) 2017/745 introduced amendments to Annex I, Section 3.2(12) of Directive 2001/83/EC. These amendments created a mandatory consultation procedure for certain drug-device combinations.

The core purpose: To ensure that when a medical device incorporates a medicinal substance with ancillary action, the EMA or a national competent authority provides a scientific opinion on the quality and safety of that substance—including its clinical benefit/risk profile.

Products That Require Article 117 Consultation

Article 117 consultation applies to devices described in MDR Articles 1(8) and 1(9), specifically:

When Is Article 117 Consultation Required?

Why this matters: Not every device with an incorporated substance requires EMA consultation. Understanding the triggers prevents unnecessary procedures—and catches requirements you might miss.

Article 117 consultation is required when a Notified Body is conducting conformity assessment for a device that incorporates an ancillary medicinal substance or human blood derivative, and the Notified Body needs an opinion on the quality and safety of that substance.

The Effective Date

Article 117 requirements apply to conformity assessment procedures initiated on or after 26 May 2021—the date the MDR came into full application.

The key trigger is whether the incorporated substance's action is ancillary to the device. If the substance's action is principal, the product is regulated as a medicinal product—not a device—and follows pharmaceutical legislation instead.

What "Ancillary" Means

A substance has ancillary action when it supports, enhances, or complements the device's primary mode of action—but the device could still function (perhaps less effectively) without it.

Post-Authorisation Changes

Article 117 consultation doesn't just apply at initial conformity assessment. It also applies post-certification if there's a major change to the incorporated substance that could impact:

• The source of the substance
• The manufacturing process
• The amount or concentration
• The method of incorporation
• Any factor affecting quality, safety, or efficacy

Procedure and Timeline: 210 Days Explained

Why this matters: The 210-day timeline doesn't run continuously. Understanding clock stops and pre-submission planning is essential for accurate project timelines.

The 210-day timeline mirrors the Centralised Procedure for medicinal products. Clock stops occur when the applicant (Notified Body) needs time to respond to questions—these periods don't count against the 210 days.

Pre-Submission Activities

EMA strongly encourages pre-submission engagement. The key elements:

Accelerated Assessment

In specific circumstances, accelerated assessment may be requested. Qualifying conditions include:

• Devices used in serious diseases (life-threatening or heavily disabling)
• Known medicinal substance or human blood derivative from a known source, where the CHMP deems the evaluation less extensive

Justification for accelerated assessment should be provided at least 10 working days before the CHMP meeting preceding the intended start of the procedure.

Documentation Requirements

Why this matters: Incomplete documentation triggers clock stops and delays. Knowing exactly what's required upfront prevents avoidable timeline extensions.

The dossier is prepared collaboratively between the device manufacturer and the Notified Body. The Notified Body takes responsibility for submission, but the manufacturer provides the underlying technical documentation.

Quality and Safety Data

The EMA assessment focuses on whether the incorporated substance meets quality and safety standards. Key areas of scrutiny include:

What Cannot Be Accepted

EMA guidance is clear on several documentation requirements:

• Partial compliance: A Notified Body opinion or compliance statement concluding on partial compliance with GSPRs cannot be accepted—full compliance is required
• Cross-references to national dossiers: It's not possible to cross-refer to the dossier of nationally authorised medicinal products
• Scope misalignment: The scope of the Notified Body opinion must align with the intended purpose of the device for the specific consultation

Roles: EMA, CHMP, and Notified Bodies

Why this matters: Understanding who does what prevents miscommunication and ensures you're coordinating with the right parties at each stage.

Post-Consultation: Managing Changes

Article 117 doesn't end with the initial opinion. Changes to the incorporated substance after CE marking require ongoing communication with EMA.

When to Consult EMA on Changes

If changes are made to an ancillary medicinal substance or blood derivative incorporated in the device, the Notified Body must:

1. Inform EMA of the proposed change
2. Consult EMA to confirm that the quality and safety of the ancillary substance are maintained
3. Receive updated scientific opinion if EMA determines the change could impact the benefit/risk profile

The Notified Body must consider any updated EMA opinion in its ongoing conformity assessment. This creates a continuous regulatory relationship, not a one-time consultation.

Changes That Trigger Consultation

Practical Guidance for Regulatory Affairs