EU/US Combination Product Services
News from EN MDR 2017/745
As you may or may not know, article 117 of the MDR 2017/745 directly amends the EU Directive 2001/83/EC concerning medicinal products for human use. This is particularly relevant for manufacturers of devices that administer medicinal products which are single integral, intended exclusively for use in the given combination, which are not reusable, and are therefore governed by Directive 2001/83/EC (see MDR article 1(9)). Hence, the MDR also has a significant impact on pharmaceutical, biotech and biosimilar companies which need a device-constituent part to deliver their medicinal product into the body of the patient.

The content of the underlying definitions and regulatory concept (e.g. which devices must be CE marked and which not) remains the same but article 117 (2nd paragraph) defines a major hick-up and possible time-consuming addition compared to Council Directive 93/42/EEC (#MDD):

“Where, if the dossier does not include the results of the conformity assessment referred to in the first subparagraph and where for the conformity assessment of the device, if used separately, the involvement of a notified body is required in accordance with Regulation (EU) 2017/745, the authority shall require the applicant to provide an opinion on the conformity of the device part with the relevant general safety and performance requirements (GSPR) set out in Annex I to that Regulation issued by a notified body designated in accordance with that Regulation [MDR] for the type of device in question.”

What does that mean?

Article 117 basically says that, although the device itself is regulated as a medicinal product and therefore not to be CE marked, a notified body needs to be involved to provide evidence (“opinion”) about compliance with the #GSPR.

Which products are affected?

  • All devices intended to administer a medicinal product that are considered to be “active” (i.e. source of energy other than generated by the human body or by gravity, e.g. battery-powered, spring-powered). If such a device was regulated as a medical device, it would be a class IIa or IIb product according to MDR Annex VIII, rule 12, and therefore require the involvement of a notified body.
  • All needle-based injection systems regardless if they are considered “active” or not and regardless if the needle is staked or delivered / provided separately; needle-based injections systems are (based on their intended use) considered being surgically invasive devices. Consequently, such devices are classified as class IIa or IIb devices according to MDR Annex VIII, rule 6*.

What are the take-away’s?

  • Ensure GSPR (General Safety and Performance Requirements) are met, regardless of the regulatory pathway
  • For products to be CE marked, address relevant topics of the MDR (i.e. Annex II and III) and get the products CE marked
  • For products regulated as medicinal products, evaluate classification of the device constituent part; if not class I, approach a Notified Body (sooner rather than later) to plan on obtaining an opinion regarding compliance with the GSPR

 *see also MEDDEV 2.4/1 rev. 9

Your partner in ensuring successful compliance with drug-device combination product requirements
Combination product requirements
Important differences exist for US and European requirements for drug-device combination products and drug delivery devices. Gemar helps companies understand these differences so that project milestones can be more efficiently reached.
EU regulatory and quality system requirements
Gemarmed can help you formulate effective regulatory and quality system strategies for the device components of combination products, and if requested, provide feedback and support with regard to the drug component as well.
US regulatory and quality system requirements
Gemarmed provides the support you need to understand and properly interpret US requirements and "grey" areas and anticipate FDA expectations, which is fundamental for the success of combination products destined for the US.
EU and US clinical study management
Gemarmed is uniquely qualified to be your partner managing and monitoring your clinical study sites throughout the EU and in the US. 
Gemarmed has the knowledge and experience to assist in the development of effective regulatory, clinical study, and quality system strategies, so that important project milestones can be met. Contact us either by e-mail for a confidential discussion about your project.