MDR Article 117 Overview: What It Means for the Pharmaceutic

Drug-device combination products—also known as integral products—are those in which the device and the medicinal substance form a single, inseparable unit. These are regulated under MDR Article 117 when:

• The device contains a medicinal substance that, if used alone, would be regulated as a drug.
   
• The primary mode of action is achieved by the medicinal component, while the device facilitates delivery or monitoring.
   

Examples of integral products include:

• Medicinal products with embedded sensors
   
• Single-use, pre-filled syringes
   
• Drug-eluting intrauterine devices (IUDs)
   
• Pre-filled dry powder inhalers
   

Non-integral products differ in that the drug and device are not physically combined during manufacturing. These do not fall under Article 117 but still require regulatory attention.

Types of non-integral products:

• Co-packaged products – Medicinal products and devices packaged together, such as a syringe and vial in a single box.
   
• Reference products – Where the medicinal product's labeling refers to a specific device obtained separately.

Examples:

• Oral dosing cups, spoons, and syringes
   
• Refillable pens and cartridge-based injectors
   
• Nebulizers, vaporizers, and pump systems
   
• Electronic tablet dispensers
   

Some devices incorporate a medicinal substance whose effect is secondary (ancillary) to the device’s primary function. While these do involve both components, their regulatory treatment differs.

Example:

• Intrauterine devices (IUDs) that release hormones, where the primary function is mechanical but includes a medicinal benefit
   

MDR Article 117 enhances patient safety and regulatory clarity by ensuring that drug-device combination products meet robust quality and performance standards. At RAPS, we’re committed to keeping you informed and compliant as regulatory landscapes evolve.

Need help navigating Article 117? Contact us today for guidance on your product strategy and Notified Body submissions.

The Medical Devices Regulation (MDR) 2017/745 (EU) introduces more rigorous requirements for medical devices and extends its scope to include drug-device combination products, significantly impacting pharmaceutical manufacturers. When a medicinal product includes a medical device as an integral component, Article 117 becomes a critical regulatory checkpoint.

Under this framework, Article 117 amends Directive 2001/83/EC (Section 3.2, Point 12) to require the involvement of a Notified Body in assessing the medical device component’s compliance with the General Safety and Performance Requirements (GSPR) outlined in Annex I of the MDR. 

For integral drug-device combination products, a Notified Body Opinion (NBOp) is required when no EU Declaration of Conformity or CE certificate is available. This involves:

• A thorough review of the device’s technical documentation
   
• Verification of compliance with all applicable GSPRs
   

Once the assessment is complete and satisfactory, the Notified Body issues an NBOp Report, which the manufacturer includes in the Marketing Authorization Application (MAA) submitted to regulatory authorities such as the European Medicines Agency (EMA).

Our experienced consultants specialize in both pharmaceutical and medical device regulations, ensuring seamless navigation through the NBOp process. We provide end-to-end support, including:

• Determining regulatory applicability for drug-device combination (integral) products
   
• Defining the product’s intended purpose and mode of action to classify the primary and ancillary components 
• Regulatory strategy planning, tailored to your product and market goals
   
• Confirming the risk classification and relevant regulatory route
   
• Identifying applicable harmonised and non-harmonised standards
   
• Performing and documenting biological evaluations
   
• Conducting risk assessments and benefit-risk analyses
   
• Preparing clinical evaluations for the device component
   
• Reviewing usability, packaging, sterility, and transport considerations
   
• Compiling full technical documentation in line with Annex I GSPRs
   
• Assisting in Notified Body selection and application preparation
   
• Coordinating communications and responding to Notified Body feedback
   
• Managing document control and revisions throughout the NBOp lifecycle