What is the role of Expert panels?
According to articles 106 and 48(6) of the Medical Device Regulation (EU) 2017/745 (MDR) and Regulation (EU) 2017/746 on In Vitro Medical Devices (IVDR), the European Commission is required to design expert panels with the aim to:
- Give opinions and views on key documents of the technical files for certain high risk medical devices, i.e., Class III implantable devices and class IIb actives devices which are intended to administer and/or remove a medicinal product and certain in vitro diagnostic medical devices, i.e., Class D devices, where no Common Specifications are available and where it is also the first certification for that type of device, respectively falling under the Clinical Evaluation Consultation Procedure (CECP) and the Performance Evaluation Consultation Procedure (PECP).
- Provide ad hoc advice to the European Commission, the Medical Device Coordination Group (MDCG), EU Countries, notified bodies and manufacturers when deemed necessary.
In the first step, the Screening panel assesses the device in question and decides whether an opinion by an Expert panel is needed based on the following criteria:
- the novelty of the device or of the clinical procedure involved have possible major clinical or health impacts;
- valid health concerns lead to a significant adverse change in the benefit/risk profile of a relevant category or group of devices;
- significant increase in the rate of serious incidents for a relevant category or group of device.
The panel provides its assessment based on the documentation received from notified bodies and manufacturers, as well as their knowledge and experience.
Taking into account the experts’ opinion, the notified body must advise the manufacturer on possible actions, such as specific restrictions of the intended purpose, limitations on the duration of the certificate validity, specific post-market follow-up (PMCF) studies, adaption of instructions for use or the summary of safety and clinical performance (SSCP) or may impose other restrictions in its conformity assessment report (Expamed, 2021).
Decision of screening experts on a class III implantable medical device
On 11 May 2021, the screening experts provided an opinion on a class III implantable medical device (Ivory Dentin Graft™) intended to be used as a bone graft material for the repair or augmentation of bone defects in dental procedures. The reasons considered for the decision to provide an opinion can be summarized as follows:
- Indication of use: The risk-benefit profile cannot be identified due to the lack of clinical evidence.
- Device dysfunction or failure in the indication of use will create major problems for the patients. Additionally, the failure of the device will lead back to the initial clinical situation for the patients without additional problems.
- Short clinical evaluation: The clinical evaluation is based only in 4-months data. Moreover, device was only compared to similar but not equivalent devices in literature and the PMCF Plan focuses on the evaluation of the same cases analyzed in the CER for a time frame of 6 months up to 5 years.
- Clinical data only for one indication: There is no data available for the 6 indications for use, causing a high clinical impact uncertainty.
- Resorption time of 5-7 years: No evidence has been provided.
The two main criteria used to assess the case are:
- Novelty of device under assessment and possible clinical / health impact: The device is a xenogeneic bone graft material and it is considered to be new. Although, the level of novelty is assessed as “medium” because the kind of the described device, the indications for use and the described treatment for application, are not new. The only novelty in the present design concerns the origin of the hydroxyapatite. The estimated severity of the clinical and/or health impact is considered to be “moderate” because it changes according to the volume of the material used for the external sinus floor evaluation. In addition, the clinical period of 4 months is not sufficient to evaluate a device failure, causing a major uncertainty on possible health effects. The clinical data given at CEAR is applicable only to one indication for use of the device. No data is available for the other 6 indications for use, not even in the PMCF plan. Another point to take into consideration is the organic/cellular remnants contained in the xenogeneic bone materials for the application in humans, as it might induce an immune response within the recipient.
- Scientifically valid health concerns leading to significantly adverse changes in the benefit-risk profile of a specific group / category of devices and relating to
- Component(s): The preservation of organic/cellular remnants coming from the animal origin can possibly induce an immune response within the recipient. This information is only indirectly relevant as it applies also to the devices applied in the market.
- Source material(s): There are health concerns also related to the resorption behavior and novel bone formation for application of higher volumes solely of the device, specifically in the maxillary sinus (no histological proof). Particularly, inflammation / unknown host reaction during resorption or non-resorption with lack of vitality for osseointegration in this indication. The proof of comparability to other materials is lacking for the device under evaluation regarding its physico-chemical structure. This implies an unknown behavior of resorption in the indication “lateral sinus augmentation” with the application of gross volumes solely of the device.
The experts also note general health concerns in view of the short term evaluation is not adequate to certify the use of the device without problems, as a longer time period is necessary to state device failures, etc. In addition, the missing clinical evidence on the 6 indications for use causes major uncertainty. The PMCF Plan does not include these indications either (Expamed, 2021).
The ‘’Criterion 3: Significant increase of serious incidents of a specific group / category of devices relevant for the device under assessment’’ was not deemed to be an applicable criterion as no information on incidents was provided by the Secretariat.
Scientific opinion by the thematic expert panel/sub-group
On 15 June, 2021, the expert panel General & plastic surgery and dentistry provided a scientific opinion reflecting the views of the screening experts on the clinical evaluation assessment report (CEAR) of the notified body. The Summary Opinion consists of:
- Device description
- Adequacy of clinical evidence assessment by notified body:
- Sufficiency of clinical evidence
- Adequacy of benefit-risk determination
- Consistency of clinical evidence with purpose/medical indication(s)
- Consistency of clinical evidence with PMCF plan
- Overall conclusions and recommendations on clinical evaluation
The device assessed is marked as a new device, but its level of novelty is moderate, as only the source of the device is new. The Notified Body’s assessment on the clinical study is questioned because of the limited period of study of only 4 months. In addition, the functionality of newly formed tissue for implant placement cannot be demonstrated as no observation time was respected. The assessment of other claimed indications is also challenged, a major issue concerns that it is based on the analysis of similar but not equivalent materials. The PMCF plan needs to be adjusted to a longer period of time of 12 months, 2.5 years and 5 years and should be specific for each indication.
Let’s focus on Overall conclusions and recommendations from the Expert panel:
The device is a xenogeneic bone graft material based on xenogeneic dentin derived particles and it is intended to be used in surgical procedures. Its level of novelty is moderate, as only the origin of the device is new. Even though it can be considered as a valuable addition to the portfolio of devices for the claimed indications, the clinical data is not sufficient to assess the possible clinical/health impact of the device. The presented clinical data for the claimed indication “filling of extraction sockets to enhance preservation of the alveolar ridge”, is insufficient and should include at least the 4-month healing phase for the implant. The results could then be used for the clinical assessment of the claimed indications “filling of defects after root resection, apicoectomy and cystectomy” and “elevation of maxillary sinus floor”. For the other indications, data from clinical studies is missing. Additionally, literature survey is affected by the fact that the new device is not equivalent, but only similar to products already on the market. The PMCF plan needs to be further elaborated.
MDlaw will inform of any new expert panel opinions published, so follow the News section for all updates!