Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Labeling of Drug-Device Combination (DDC) Products in Europe under the new Medical Device Regulation (EU) 2017/745 ***

Dr. Denise Nadine Fabian (Abschlußjahr: 2023)

Summary
Language: English
With the entry into force of the new Regulation (EU) 2017/745 (MDR) applicable for medical devices on 26 May 2021, the labeling requirements for drug-device combination (DDC) products, among other things, were affected. In this thesis, labeling requirements for DDC products, including co-packaged and integral DDCs regulated either as a medical device or medicinal product, according to the new MDR were assessed and challenges for medical device manufacturers and marketing authorization holders were highlighted and discussed.
The main labeling requirements applicable for medical devices are listed in Annex I "General safety and performance requirements" of the MDR. Compared to medicinal products, for which detailed additional guidance documents published by the European Medicines Agency (EMA) are available, hardly any additional labeling guidance is available for medical devices at the moment. The medical device coordination group (MDCG) started to publish additional guidance for several other topics related to the implementation of the new MDR, but no labeling paper is published yet. In the MDR, manufacturers are advised to consider internationally harmonized standards, e.g. ISO standards, which are often not publicly available and request the purchase of a license to be reviewed and considered. For some medical devices only an electronic instructions for use (eIFU) is required. EMA has initiated a project for implementing electronic product information (ePI) for medicinal products but up to now no such initiative includes and considers the electronic labeling of medical devices, e.g. eIFUs or ePIs. This is an additional task which should be added to the worklist of the MDCG and EMA. An initiative, starting an exchange between the two working groups for medicinal products and medical devices may also lead to an improvement of the overall quality of labeling documents considering the harmonized approach of the creation and assessment of the labeling for medical devices or DDCs.
In addition to the missing labeling guidance for DDC products, the different applicable approval and registration processes were accessed. For DDCs regulated as a medical device, a conformity assessment performed by a notified body is needed for placing the DDC on the European market. For DDCs regulated as a medicinal product, a two-step approach is applicable including a notified body opinion (NBOp) assessing the safety of the medical device part followed by a benefit-risk assessment for the medicinal product, i.e. the integral DDC, performed by EMA. Up to now, no direct interaction between the designated notified body and EMA is foreseen. Therefore, it is unclear how any comments or changes requested by EMA related to the medical device component can affect the approval process of the integral DDC or the notified body opinion.
For the future, the release of further labeling guidance for medical devices and DDCs would be desirable. First of all, this would improve the quality of the labeling documents for medical devices due to a harmonized approach. Harmonized labeling documents might ease the review process performed by notified bodies and EMA for registering and approving a DDC. At the moment, manufacturers can choose from a list of various notified bodies for performing the assessment and medical devices are very diverse so that a consistent assessment would be desirable for a smooth and fair approval of DDCs. In addition, a harmonized approach will most likely improve the safety and effectiveness of DDCs. Information will be easier to find and understand for the intended user if labeling documents are set up in a similar manner. Even though the MDR requires that the labeling should be readable and understandable, no guidance is available what this exactly means, how it is ensured by the manufacturers or assessed by the notified bodies or how it can be tested by the manufacturer prior applying for a conformity assessment. EMA started to provide some guidance for DDCs regulated as medicinal products. Nevertheless, no such guidance is accessible from the MDCG for medical devices or DDCs at the moment. Therefore, it is to be hoped that the MDCG will also consider the labeling as an important part of the medical device assessment and considers publishing further guidance documents in future. These documents could include labeling templates with additional explanations how to interpret and implement the MDR requirements comparable to the QRD templates published by EMA for medicinal products. In addition, it is desirable that EMA may consider an update of their available labeling documents to provide further guidance for DDC products increasing the focus on the medical device part.
Furthermore, it needs to be awaited if additional guidance regarding the approval of DDCs including a NBOp and EMA assessment is published, e.g. by EMA, in future. Due to the strict split of the technical assessment for the medical device part performed by the notified body and the benefit-risk assessment performed by EMA for the medicinal product part, no exchange and communication between these two assessment parties is foreseen. If this is planned to be the future process, further guidance specifying the requirements for a re-assessment by the notified body is needed in case EMA requests major changes of the labeling documents. Any change of the labeling documents can have a potential impact on the design development and therefore also the performed risk-assessment of a medical device and may potentially lead to a re-assessment. Respecting the transition period, only few DDCs might have been assessed by EMA up to now and marketing authorization holders as well as notified bodies and EMA need to gain further experience in the assessment of DDCs before a conclusion of the impact of the new MDR requirements on the overall approval process can be made. Nevertheless, a highly structured and transparent approval process as currently performed and published by EMA would be highly beneficial to be implemented for medical devices as well. Considering especially the number of different notified bodies and the potential imbalance of performed assessments due to no harmonized approach. For manufacturers, it would be also a benefit to better understand the requirements and timelines so that they can improve the planning and registration process of their medical devices.
Pages: 61
Annexes: 13, Pages: 85