Quick Contact
MDR Article 117
Attention pharmaceutical industry, this is for you. MDR Article 117 of the Medical Device Regulation has amended Directive 2001/83/EC, Section 3.2, Point 12, mandating the involvement of a Notified Body for the issuance of a “Notified Body Opinion” for drug device combination products as a single integral device. Manufactures can use the Notified Body Opinion to include it in the Market Authorization Application to the European Medicines Agency.
The above article is applicable for devices where the manufacturer’s EU declaration of conformity and the relevant EU certificate issued by a notified body are not available.
Drug Device Combination Products
For a better understanding, drug device combination products, also known as integral products, are defined as follows:
- A medical device that incorporates a drug or medicinal substance as an integral part that, if used separately, is considered a drug or medicinal product and whose substance action is principal Examples; medicinal products with embedded sensors.
- A medical device intended to administer a drug or medicinal product that constitutes a single integral product intended exclusively for use in combination and which is not reusable Examples; single-use pre-filled syringes, drug-releasing intrauterine devices, and single-use pre-filled dry powder inhalers.
Non Drug Device Combination Products
Medicinal and device components that are not physically integrated during manufacturing but are combined before human administration, so-called non-integral products, are not covered in drug-device combination products. Such types of products are detailed below.
- Co-packaged products – The medicinal product and the medical device are placed on the market and packed together into a single pack.
- Reference product – The medicinal product information (SmPC and/or package leaflet) is for a specific medical device that must be obtained separately.
A few examples of non-integral products are: cups, spoons and syringes for oral administration, refillable pens and injectors using cartridges, nebulisers, vaporisers, pumps for medicinal product delivery and electronic tablet dispensers.
- Ancillary Medical Devices – If the device incorporates a substance as an integral part that, if used separately, is considered a medicinal product, but the action of the substance is ancillary to that of the device. Examples are intrauterine device (IUD)
With the new MDR 2017/745, MDR Article 117 has brought significant impact. It now requires that the device portion of integral drug-device combination products must have an evaluation from a Notified Body to ensure compliance.
MDR Article 117 Regulatory Framework
The new Medical Devices Regulation (MDR) 2017/745 (EU) sets stringent requirements on medical device manufacturers and notified bodies and broadens the scope to include the pharmaceutical industry about pharmaceuticals with a medical device as an integral component.
To determine whether a device part complies with the pertinent GSPR of Annex I, a notified body must be involved by MDR Article 117, which amends Directive 2001/83/EC, point 12 of Section 3.2.
Notified Body Opinion Report
A Notified Body conformity assessment of drug-device combination products coming under the preview of MDR Article 117 entails an examination of the technical documentation in relation to all applicable General Safety and Performance Requirements (GSPRs) stated in Annex I of the MDR.
After the technical documentation review is completed successfully, a Notified Body will issue an Notified Body opinion Report. This opinion can subsequently be included in the drug device combination product’s Marketing Authorization Application (MAA) submitted to a drug competent body such as the European Medicines Agency (EMA).
NBOp and Role of I3CGlobal Consultants
| No. | Consultant Activities |
|---|---|
| 1 | Establish whether the product qualifies as a drug–device combination or an integral product. |
| 2 | Define the intended purpose and mode of action to identify the principal and ancillary components. |
| 3 | Develop the regulatory strategy and route plan based on pharmaceutical and medical device expertise. |
| 4 | Confirm the medical device risk classification and applicable regulation and rule number. |
| 5 | Identify applicable harmonized and non-harmonized standards. |
| 6 | Perform and support biological evaluation in line with regulatory requirements. |
| 7 | Conduct risk analysis and benefit–risk assessment for the combined product. |
| 8 | Prepare and review the clinical evaluation of the medical device. |
| 9 | Assess device usability, sterility, packaging, and transportation requirements. |
| 10 | Compile and structure documentation in accordance with General Safety and Performance Requirements (GSPR). |
| 11 | Support the manufacturer in identifying and selecting a suitable Notified Body. |
| 12 | Assist with the Notified Body application and submission. |
| 13 | Coordinate communication and respond to Notified Body queries during technical documentation review. |
| 14 | Manage document control, revisions, and updates throughout the Notified Body Opinion process. |
I3CGLOBAL offers a team of QARA experts to assist with arranging Notified Body Opinion letters, by preparing technical documentation, interacting with Notified Bodies, by correctly implementing requirements to ensure compliance with MDR Article 117.
Frequently Asked Questions
Which documents are required to be submitted to the Notified Body?
Timeline for Notified Body Opinion Letter
After providing the technical documentation in accordance with the GSPR, the Notified Body will conduct a preliminary review and accept the file. Typically, the full initial review of technical documentation takes 10 to 12 weeks. The timeline for the entire review process is determined by the compliance and objective evidence submitted against each section of the GSPR. The timeline is determined by the number of additional review rounds and questions posed by the notified body, as well as the manufacturer’s responsiveness in appropriately addressing the review points.