Transitional provisions for consultations of authorities on devices incorporating a substance which may be considered a medicinal product and which has action ancillary to that of the device, as well as on devices manufactured using transmissible spongiform encephalopathy (TSE) susceptible animal tissues.
The European Commission provides a range of guidance documents to assist stakeholders in implementing the medical devices regulations.
Legally non-binding guidance documents, adopted by the medical device coordination group (MDCG) in accordance with Article 105 of Regulation 745/2017, pursue the objective of ensuring uniform application of the relevant provisions of the regulations within the EU.
On June 10th, 2020, the Medical Device Coordination Group (MDCG) released its guidance on transitional provisions for consultations of authorities on devices incorporating a substance which may be considered a medicinal product and which has action ancillary to that of the device, as well as on devices manufactured using transmissible spongiform encephalopathy (TSE) susceptible animal tissues.
What does this mean to you?
If you have a medical device that incorporates a substance which may be considered a medicinal product and which has action ancillary to that of the device, or a device manufactured using transmissible spongiform encephalopathy (TSE) susceptible animal tissues, then you will have to familiarise yourself with this guidance and take the stipulated timelines into consideration.
Different Scenarios
A manufacturer needs to consider two different scenarios to obtain CE approval for medical devices incorporating a substance which is considered a medicinal product.
1. There is the process which is to be followed for new medical devices under the MDR
In this case the manufacturer will compile the Technical Documentation and submit it to the Notified Body. The Notified body then performs an assessment regarding the usefulness of the substance as part of the medical device, taking account of the intended purpose of the device.
In addition the Notified Body will have to seek a scientific opinion from a competent authority responsible for assessment and approval of pharmaceuticals or with the European Medicines Agency (EMA). The assessment of the CA will focus on the quality and safety of the substance in the medical device, including the clinical benefit/risk profile of the incorporation of the substance into the device. This process is called “consultation procedure”.
Steps in the consultation process include: (1) consultation request by the Notified Body (NB) to the relevant CA/EMA, (2) pre submission procedure, usually including also a meeting to be attended by the NB and the manufacturer, and (3) the final submission of the dossier for review. The CA/EMA will provide an assessment report at the end of the review process, within 210 days, with their overall opinion on the quality and safety of the drug substance. In contrast to the MDD, under the MDR the NB shall not deliver the certificate if the scientific opinion is unfavorable.
It is interesting to note that in rule 14, which is applicable for combination products, the wording “liable to act on the human body” was purposefully removed from the MDR. That means that a device that incorporates even only some molecules of a medicinal substance will always fall under rule 14 regardless of the concentration of this substance. Hence many devices that previously found. an ‘escape route’, now will be classified as combination products.
2. Consultation procedure under MDR with existing certification under MDD
In order for the notified body to issue the first certificate for a given device under the MDR, a full conformity assessment covering all requirements has to be carried out even if the device has been certified under the MDD (Q&A IV.1 MDCG 2019-6). For devices containing ancillary substances, this includes the consultation of the medicinal products authority as per Article 52 (9) of the MDR.
For some devices, no change to the device, the ancillary substance and its manufacturing process since the last consultation of the medicinal products authority under the MDD/AIMDD has occurred.
Nevertheless, there may be changes in the documentation of the device due to the new requirements of the MDR, for example in clinical evaluation part, which have a bearing on the quality, safety or usefulness of the ancillary substance. There may also be changes in the assessment of the device and its documentation by the notified body under the MDR. Lastly, the medicinal products authority may have new information on the substance, leading to a modified or different opinion.
For the first consultation under the MDR, the notified body is required to submit the full documentation package to the medicinal products authority as described in dedicated guidance. The notified body is free to approach any medicinal products authority at its discretion, not necessarily the one consulted under the MDD/AIMDD.
If there were no changes to some or any of the above, the package may be accompanied by a declaration by the notified body to this effect, stating the elements that have remained identical. If there have also been no changes to the assessment of this documentation by the notified body, this may be included in the declaration. Should there be only administrative changes to the above (e.g. changes of names or addresses, changes in document layout, etc.), these should be clearly detailed in the declaration.
Since the MDR requires several changes to the labeling of the devices, it remains to be seen, if the medicinal products authorities will consider these changes “administrative changes”.
The medicinal products authority may consider the depth of its review given the extent of the changes since the previous consultation under the MDD/AIMDD. It is at the discretion of the medicinal products authority to issue its opinion in less than 210 days. If many elements concerning the substance remain identical, the medicinal products authority is (per MDCG 2020-12) highly recommended to expedite its review.
The medicinal products authority may contact the authority consulted on this device under the MDD/AIMDD, who may, at its discretion, confirm the opinion provided in the previous consultation and/or share any additional information. The final opinion for the consultation under the MDR and its issuance according to the stipulated timeline remains the responsibility of the medicinal products authority to which the notified body submitted the request under the MDR.
In summary it can be concluded that
The medicinal substance-based parts of the Technical File need to be reviewed by a Competent Authority again. From a timing perspective, legal manufacturers will have to consider the time required for the review of the Notified Body and the 210-day review time by the medicinal products authority to which the notified body submitted the request.
Therefore, an additional 7 months’ timeframe needs to be considered at minimum, before a MDR certificate for a substance-based class III medical devices, which have formerly been certified under MDD can be expected.
Even if the Notified Body decides (typically with consent of the manufacturer) to submit to the same Competent Authority, which has originally been consulted to obtain the MDD certificate, there is the risk that this authority might change its opinion on the quality and safety of the drug substance, based on new information on the substance. Choosing a different Competent Authority bears the risk that this authority might have a different view to the substance used.
Additionally, MDR offers the option to the Competent Authorities (and Notified Bodies) to re-assess combination and substance based medical devices under the State-of-the-Art and bisk/benefit aspect!
Close cooperation with the Notified Body, the choice of a medicinal products authority, which is familiar with the specific substance and has experts available for the review and a good planning of the submission project, including the extended timing to obtain an approval is paramount to receive MDR certificates for these devices as soon as possible.
Qserve has experts on combination product submissions available and is happy to support manufacturers to transfer medical devices from MDD to MDR compliance.