Regulatory Update: Medical Devices

Impact of MDR, Article 117 medicinal products with an integral medical device

BY Stephan Buttron, Principal Regulatory Affairs Consultant, Parexel - 11.21.19

The medical devices regulation (MDR) and in-vitro diagnostics regulation (IVDR) replace the three current Directives (93/42/EEC, 98/79/EC and 90/385/EEC) for medical devices. The Regulations were published on 25 May 2017; however, they will have a three (3) year transition period to allow manufacturers, notified bodies and authorities to comply with the changes until May 26, 2020 for medical devices and 26 May 2022 for in vitro diagnostics.

Article 117 of the Medical Device Regulation 2017/745  is amending Annex I to Directive 2001/83/EC, point 12 of section 3.2), and introduces a new requirement for notified body involvement in a medicinal product with an integral medical device.

The marketing authorization dossier for a medicinal product with an integral medical device is expected to include the results of the assessment of conformity for the medical device component to the general Safety and performance requirements laid down in Annex I of the Regulation (i.e. the declaration of conformity or the relevant certificate issued by a notified body).

If the ancillary medical device is not CE marked and an EU certificate from a notified body would be required if the medical device was used separately, then the applicant must provide an opinion from a notified body on the conformity of the device part with relevant requirements of Annex I to Regulation 2017/745 as part of the marketing authorization application.

This requirement applies to medicinal products that form an integral product with a medical device, where the mode of action of the medicinal product is principal and where a medical device is used to administer a medicinal product.

Article 117 does not apply in the case of combined advanced therapy medicinal products as defined under Article 2(1)(d) of Regulation (EC) No 1394/2007.

When is my medicinal product considered to form an integral product with the administration device?

If a medical device used to administer a medicinal product is placed on the market in such a way that the device and medicinal product form a single integral product which is intended exclusively for use in the given combination and which is not reusable, that single integral product shall be governed by Directive 2001/83/EC or Regulation (EC) No 726/2004, as applicable.

The second paragraph of Article 1(9) of the MDR defines  three (3) cumulative conditions that need to be fulfilled at the moment of the placing on the market:

1.      The delivery device and the medicinal product form a single integral product;

2.      Intended exclusively for use in the given combination;

3.      and is single use only.

For medicinal products meeting all above conditions, the single integral product shall be governed by the medicinal products Directive, however, the relevant general safety and performance requirements set out in Annex I to Regulation 2017/745 shall apply as far as the safety and performance of the device part of the single integral product are concerned.

Examples of integral products which are not reusable are:

·         pre-filled syringes,

·         pre-filled pens,

·         nebulizers pre-charged with a specific medicinal product,

·         patches for transdermal drug delivery and pre-filled inhalers.

An example of a combination which is not considered an integral product is a vial containing a drug solution with an (empty) co-packaged syringe.

How will the medical devices Regulation and in particular Article 117 impact new marketing authorization applications?

Marketing authorization applications for a medicinal product with an integral medical device submitted as of 26 May 2020, must demonstrate that the device part meets all relevant safety and performance requirements of Annex I of Regulation (EU) 2017/745.

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To provide further clarity regarding Article 117, the European Medicines Agency (EMA) has issued a comprehensive guidance on the matter and expects to provide further information on aspects where EMA activities may interact with MDR and the In Vitro Diagnostic Regulation (IVDR) 2017/746.

Although there is still work in progress with regards to the process of receiving Notified Body feedback, the depth of the assessment, content and validity period as well as change notifications affecting the “expert opinion” remains still unclear.

The EMA guidance document, may be found here.

The medical devices regulation (MDR) and in-vitro diagnostics regulation (IVDR) replace the three current Directives (93/42/EEC, 98/79/EC and 90/385/EEC) for medical devices.  The Regulations were published on 25 May 2017; however, they will have a three (3) year transition period to allow manufacturers, notified bodies and authorities to comply with the changes until May 26, 2020 for medical devices and 26 May 2022 for in vitro diagnostics.

Article 117 of the Medical Device Regulation 2017/745  is amending Annex I to Directive 2001/83/EC, point 12 of section 3.2), and introduces a new requirement for notified body involvement in a medicinal product with an integral medical device.

The marketing authorization dossier for a medicinal product with an integral medical device is expected to include the results of the assessment of conformity for the medical device component to the general Safety and performance requirements laid down in Annex I of the Regulation (i.e. the declaration of conformity or the relevant certificate issued by a notified body).

If the ancillary medical device is not CE marked and an EU certificate from a notified body would be required if the medical device was used separately, then the applicant must provide an opinion from a notified body on the conformity of the device part with relevant requirements of Annex I to Regulation 2017/745 as part of the marketing authorization application.

This requirement applies to medicinal products that form an integral product with a medical device, where the mode of action of the medicinal product is principal and where a medical device is used to administer a medicinal product.

Article 117 does not apply in the case of combined advanced therapy medicinal products as defined under Article 2(1)(d) of Regulation (EC) No 1394/2007.

When is my medicinal product considered to form an integral product with the administration device?

If a medical device used to administer a medicinal product is placed on the market in such a way that the device and medicinal product form a single integral product which is intended exclusively for use in the given combination and which is not reusable, that single integral product shall be governed by Directive 2001/83/EC or Regulation (EC) No 726/2004, as applicable.

The second paragraph of Article 1(9) of the MDR defines  three (3) cumulative conditions that need to be fulfilled at the moment of the placing on the market:

  1. The delivery device and the medicinal product form a single integral product;
     
  2. Intended exclusively for use in the given combination;
     
  3. and is single use only.

For medicinal products meeting all above conditions, the single integral product shall be governed by the medicinal products Directive, however, the relevant general safety and performance requirements set out in Annex I to Regulation 2017/745 shall apply as far as the safety and performance of the device part of the single integral product are concerned.

Examples of integral products which are not reusable are:

  • pre-filled syringes,
     
  • pre-filled pens,
     
  • nebulizers pre-charged with a specific medicinal product,
     
  • patches for transdermal drug delivery and pre-filled inhalers.

An example of a combination which is not considered an integral product is a vial containing a drug solution with an (empty) co-packaged syringe.

How will the medical devices Regulation and in particular Article 117 impact new marketing authorization applications?

Marketing authorization applications for a medicinal product with an integral medical device submitted as of 26 May 2020, must demonstrate that the device part meets all relevant safety and performance requirements of Annex I of Regulation (EU) 2017/745.

 


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