As we all know, there are continuous updates to the existing technologies alongside the advent of new ones. Incorporating these technologies into the drug-device combination products for tracking and monitoring purposes is increasing day by day. Given the continuous technological developments and wide range of medical devices or device parts that may be used with a medicinal product, it is essential to have appropriate guidelines on what type of information should be provided in a combination product’s Regulatory submission.

The EMA recently released a guidance document describing how qualitative the dossiers (Marketing Authorization Application (MAA) or Post-authorization Application) should be presented for a medicinal product when used with a medical device or a device part. As the dossiers must be submitted following the Directive 2001/83/EC and/or Regulation (EC) 726/2004, the current guidance document focuses on the product-specific quality aspects of a medical device or device part that may have an impact on the quality, safety and efficacy of a medicinal product.

The new guidelines will come into effect from January 1, 2022. Below mentioned are some of the key points that must be considered.

Firstly, the EMA guidelines are applicable to three (03) types of combination products as described below.

1. Medicinal products, where a medical device and/or a device part in combination with a medicinal product form an integrated product that is not reusable (hereafter called integral) and where the action of the medicinal product is principal. Examples of integral products include:
   • single-use pre-filled syringes
   • single-use pre-filled pens and single-use pre-filled injectors (including auto injectors)
   • pre-assembled, non-reusable applicators for vaginal tablets
   • dry powder inhalers and pressurized metered-dose inhalers that are pre-assembled with the medicinal product and ready for use with single or multiple doses that cannot be refilled when all the doses are exhausted
2. Medicinal products are placed on the market by the Marketing Authorization Holder (MAH), where the medical device is packed together with the medicinal product (hereafter called co-packaged).
3. Medicinal products, where the product information refers to a specific medical device to be used with the medicinal product, and the medical device is obtained separately by the user of the medicinal product (hereafter called referenced).

Examples of co-packaged or referenced products include:

• oral administration devices (e.g., spoons, syringes)
• injection needles
• refillable/reusable pens and injectors, including auto injectors

The current guidance document doesn’t include the following in its scope:

• Veterinary products
• In-vitro diagnostic devices, including companion diagnostics
• System and procedure packs regulated under Article 22 of the MDR
• General groups of devices where reference is directly made, or inferred, in the product information (e.g., “using a syringe or “an infusion line,” etc.)
• Products falling under the first sub-paragraph of MDR Article 1(8)

Dossiers, Format, and Data Submission

Following the eCTD format, the relevant information on the device part should be presented in a clear and structured manner. The product information for integral medicinal products, co-packaged or referenced devices should follow the requirements of the Directive 2001/83/EC or Regulation (EC) No 726/2004 and should not include any administrative information on the device. They include:

• Module 1, Product Information
• Module 3.2.P, Drug Product (Description and composition, pharmaceutical development, Manufacturing process development, Container Closure System (CCS), Microbiological attributes, Compatibility, Controls of critical steps and intermediates, Process validation and/or evaluation and Stability)
• Module 3.2.A.2, Adventitious Agents Safety Evaluation
• Module 3.2.R, Regional Information, Medical Device

While this guidance document provides the information that should be included in an MAA or post-authorization application, the drug-device combination products’ manufacturers must stay abreast of the Regulatory requirements on time. Are you willing to market your drug-device combination products in the EU regions? Consult Freyr - proven Regulatory expert for compliance; stay informed and stay compliant.