Maven

Medical Devices With Ancillary Medicinal Substances

Introduction

As per EU MDR 2017/745 – Any device that, when placed on the market or put into service, incorporates, as an integral part, a substance that, if used separately, would be considered to be a medicinal product as defined in point 2 of Article 1 of Directive 2001/83/EC, including a medicinal product derived from human blood or human plasma as defined in point 10 of Article 1 of that Directive, and that has an action ancillary to that of the device, shall be assessed and authorized in accordance with this Regulation.

Examples of medical devices with ancillary medicinal substances are drug-eluting stents, catheters coated with heparin or an antibiotic agent, blood bags containing anticoagulants or preservation agents, metered dose inhalers, etc.

Applicable Regulation

Following directives are applicable for the device with ancillary medicinal substances;

Medical Devices:

Medicinal Products Directive:

  • Regulation 726/2004: Establishment of European Medicines Agency (EMA) Directive 2001/83/EC Medicinal products for human use
  • Amended Directives 2002/98/EC; 2004/24/EC and 2004/27/EC.

Documentation Requirements

Apart from general documentation requirements enclosed in the IVDR Annex II or MDR Annex II, requirements set out in the Notice to Applicants Volume 2B shall also need to be catered to.

The notified body, after receipt of technical documentation from the manufacturer, consulted the competent authority constituted for the respective member state or European Medicines Agency (EMA) for medicines falling under regulation EC 726/2004. Here, competent authority refers to the body that assesses the usefulness of the medicinal substances incorporated in the device with respect to its quality, safety and benefit/risk profile. The review is conducted in a parallel fashion by the competent authority and the notified body.

Appendix

EMA published the required documentation for consultation on the site. The required documents are as follows:

Appendix 1: Data requirement and format for application dossier

European Medicines Agency recommendation on the procedural aspects and dossier requirements for the consultation of the European Medicines Agency by a notified body on an ancillary medicinal substance or an ancillary human blood derivative incorporated in a medical device or active implantable medical device

Appendix 2: Scientific explanation for qualification

Guideline on the quality requirements for drug-device combinations

Appendix 2 discusses about the requirements of Article 117 of the EU MDR 2017/745 and the detailed requirements for Notified Body involvement in a medicinal product that incorporates a drug-device combination product. Manufacturer needs to comply with those requirements.

Additionally, marketing authorization is required for the ancillary medicinal substance as per Annex I, Section 3.2 (12) of the MPD Medicinal Products Directive 2001/83/EC which concerns documents that need to be submitted to the competent authority assessing marketing authorization applications (MAAs) for medicinal products incorporating a device as an integral part. It is necessary to submit the results of the assessment of the device part with the relevant General Safety and Performance Requirement (GSPR) set out in Annex I of EUMDR.

In cases where medicinal products are used separately and are not part of the device, and the dossier does not contain results of such a combination, notified body conformity with relevant GSPRs needs to be provided.

The list of products that are covered is mentioned in the second subparagraph of Article 1(8) and the second subparagraph of Article 1(9) of the MDR.

Stages Of Consultation

There are two stages to the consultation initial consultation and Post Consultation. The details are as follows:

Initial Consultation:

For the first consultation with the competent authority, an “initiation to submit” letter is to be provided to the competent authority before submitting an application to the competent authority. Generally, the date is six months prior to the final submission to the notified body. Once the opinion from the competent authority is received by the notified body, changes in the manufacturing process are provided to the manufacturer; this is known as initial consultation.

If the competent authority’s opinion is scientifically unfavourable in such a case, it will not provide a certificate.

Post Consultation:

After changes are made with respect to the ancillary medicinal substances manufacturing process, the notified body further consults with competent authorities to ensure the quality and safety of ancillary substances are maintained in the post-consultation stage.

Once all these requirements are fulfilled, a certification from a competent authority is issued for the device with ancillary medicine for its safety and quality. Then the Notified Body provides the conformity assessment certification to the manufacturer.



Author – Vivek Nimkar

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