The European Medicines Agency (EMA), which looks after the pharmaceutical sector in the market operating under European Union’s, has started to issue guidelines and explanations on Medical Devices Regulation (MDR) compliance related issues for the medical device and drug combination products having components of drug and medical device units and thus manufacturers should be aware of that.
As per the EMA website, the agency issued draft guidelines in June 2019 covering quality and regulatory requirements for combination medicinal products for public consultation which incorporate device components, or drug-medical device combination products. The guidelines precisely talk about Article 117 of the MDR, which will result in new compliance obligations for manufacturers of medical drug-device combination products. EMA intends to finalize the draft guideline before the regulation is in full effect on 26 May 2020.
Demystifying Requirements on Combination Products
There are two types of medical device combinations with drugs:
Integral Combination Products: The medicinal item and medical device constitute a unitary integrated medical product for instance patches for transdermal drug supply, pre-filled pens and syringes, and pre-filled inhalers etc.
Co-packaged Combination Products: The medicinal product and the device are distinct units contained in the same parcel for instance tablet delivery system with pain managing controllers, and reusable pen for insulin cartridges etc.
EMA and Notified Body roles under MDR Article 117
In the beginning of 2019, EMA issued a Question and Answer document for manufacturers and makers of drug-device combination products that will have to comply MDR Article 117 regulatory requirements subsequent year. EMA identifies that Article 117 of the Regulation needs Notified Body participation for European market approval of a medicinal product that integrates an essential medical device, or drug-device combination product.
As per the EMA, the Q/A sessions, it reflected that it will apply to medicinal products that form an integral product with a medical device, where the primary action is related to the medicinal product i.e. those devices that fall under second subparagraph of Article 1(8) and where a medical device is utilized to manage a medicinal product, i.e. it falls under second subparagraph of Article 1(9) of the MDR.
Some major issues resolved by the EMA Q&A incorporates:
For compliant medicinal drug-device combination products, marketing approval dossiers should incorporate results of conformity assessment or CE Mark allotted by Notified Bodies for device parts. For medical device parts; devoid of CE Marking, manufacturers will have to provide views from Notified Bodies concerning conformity of those parts against MDR requirements.
So as to fall under MDR Article 117 requirements, a medical product’s device and medicinal parts must constitute a “Unitary integral product;” the product must be envisioned for utilization merely in the drug-device combination; and the product must not be designed for reuse.
For new applicants of combination products looking for marketing approval, a CE Mark or the Declaration of Conformity will be needed for the medical device component of a drug-device combination product, which will support to identify whether the device part meets MDR requirements provided in Annexure I of the Regulation. Or else, applicants must offer related views from Notified Bodies proving conformity to MR Annexure I rules.
Drug-device combination products presently approved for marketing in the European Union or those whose applications will be provided before the May 26, 2020 MDR enforcement date will not be impacted by MDR Article 117 requirements, according to the EMA explanation in Q/A. But such products may become focus of MDR Article 117 requirements if manufacturers incorporate considerable changes to, substitute or add medical device parts to their products.
Documentation
The EMA draft guideline encompasses the documentation anticipated for drug-device combinations (DDCs) in the quality section of the dossier for approval of marketing application. DDCs coming under the scope of this second draft guideline by the EMA are devices that are integral to the medicinal product, co-packaged with the medicinal product or identified in the medicinal product information and purchased separately.
The guideline also explicates the integral DDCs and non-integral DDCs, with details on what the various components should incorporate, and explains how approval of marketing application for an integral DDC should incorporate proof of the compliance of the device part with the pertinent General Safety and Performance Requirements (GSPRs). A non-integral drug-device combination should be CE marked according to MDR.
General Considerations for Submitting Data, Scientific Advice, and Platform Technology
A new format or template for the incorporation of notified body view or opinion on the compliance of a device to the associated GSPRs stated under MDR is given in the draft guideline too. EMA hopes that these guidelines will increase transparency and information consistency during submissions to regulatory authorities, improving work productivity, and elevating the safety of patients in the long run. The EMA has put forth these guidelines for a three months public consultation, with the objective of releasing a finalized version of the new draft guideline before the application of the MDR’s 26 May 2020.
Preparing for the Combination Products in EU
If you company is dealing with any of the given types of device drug combination products, you should think seriously how the new MDR is going to influence it by regulatory enforcement. Therefore, understanding the EMA guidelines are important. We also understand that the companies cannot afford to navigate the extended text of guidelines and regulations. TS Q & E can offer suitable consultancy on the changes which should be tailored in your product documentation, and for submission to the regulatory bodies.
