Among the many daily activities performed by a medical device manufacturer, uniform compliance to the MDR for technical documentation is an especially time-consuming challenge. At Qserve Group, we are here to help analyze and identify a wide array of potential gaps across Clinical Evaluation reports, as well as technical documentation (such as Design Dossiers and Technical Files). An awareness of potential compliance gaps is an important first step towards planning a pathway to MDR compliance. As such, we would like to highlight several common gaps that are present in technical documentation being transitioned from the MDD to the MDR.
Clinical Evaluation Reports (CERs)
Chapter VI of the MDR covers the requirements concerning Clinical Evaluation and Clinical Investigations. A detailed guidance on Clinical Evaluation also exists (MEDDEV 2.7/1, Revision 4). Although MEDDEV 2.7/1 is not legally binding, most Notified Bodies require manufacturers to comply with MEDDEV 2.7/1 Revision 4 when performing clinical evaluations for medical devices.
In addition, while it is specific to the MDD, MEDDEV 2.7/1 Rev. 4 is regarded as a “stepping stone” to MDR compliance and contains many specifics which are not explicitly in the MDR at this time; however, they are extremely likely to be de facto requirements under the MDR.
Common gaps we have noticed for CERs, under the provisions of the MDR and MEDDEV 2.7/1 Rev. 4, include:
1. Lack of Clinical Evaluation Plans (CEPs) - under Annex XIV, manufacturers shall establish and update a clinical evaluation plan (CEP), including appropriate scoping of the clinical data provided, and providing criteria of how this clinical data is to be appraised. The MEDDEV 2.7/1 Rev. 4 also requires this CEP as a demonstration of the planning stage for a CER, which is often missing.
2. Establishing Equivalence – the MEDDEV 2.7/1 Rev. 3 requirements for demonstrating equivalence have been updated and are now more stringent under Revision 4, as well as the MDR. Full demonstration of clinical/biological/technical equivalence in device characteristics must be performed, taking into consideration all requirements of MEDDEV 2.7/1 Rev. 4. Some key points for manufacturers to consider.
a. If the equivalence route was previously established via comparison to a competitor device, the Notified Body will now challenge access to the competitor device’s technical documentation. Under the MDR, for a Class III/implantable device, a contract with the owner of the equivalent device or demonstration of full access to the technical documentation of the equivalent device, will be required. In most cases, this type of access to proprietary information is not available, and manufacturers will need to reconsider their equivalence route – whether by using a different route of clinical evidence altogether or using their own devices for establishing equivalence.
b. In the case that the equivalence route is performed using only the manufacturer’s own devices (or if a contract is in place between two manufacturers of the comparator devices), the criteria for biological and clinical equivalence provided in the MEDDEV 2.7/1 Rev. 4 are clear. However, the technical criteria are broader and would need to be defined on a case-by-case basis, to cover the type of device under evaluation. The manufacturer must justify the specific technical criteria chosen to justify equivalent design and critical performance specifications, for example. One way this might be done is via leveraging product specific standards. Oftentimes, ‘’substantial equivalence’’ table, as required by the FDA, is substituted into a CER, but this is not the same requirement as determining equivalence under the MDR or MEDDEV 2.7/1 Rev. 4.
c. Once the technical criteria are clear and justified, a table of the specific clinical, technical and biological criteria for the device under evaluation vs the equivalent device(s) should be given. The Notified Body will then question any differences and why they are not significant, from the point of view of clinical safety and performance requirements as established for the main device (the subject of the CER). They will ask where the specific information for the comparator devices was derived from if the same test method was used to derive this information. Additionally, in the case of a significant deviation in results, a medical professional will need to make a formal justification of the clinical significance of the deviation.
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Literature search strategies need to be fully developed per MEDDEV 2.7/1 Rev. 4, especially considering specifics such as: using PICO/MOOSE methodology in developing search terms, demonstrating Boolean logic in search strings, and including provisions to dictate how weighing of the articles is performed. Additionally, the person responsible for performing the literature searches should be listed and should have all the expertise required under MEDDEV 2.7/1 Rev. 4. A PDF copy of the literature search can be added to the CER, to show how the literature search was performed and its results, rendering the search reproducible.
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Post-Market Clinical Follow-Up (PMCF) - Every medical device (Class I and up) needs a PMCF process, per Annex XIV Part B, the output of which would need to include PMCF activities (examples given in Annex XIV Part B 6.2 a and b). Manufacturers must justify appropriately not performing a PMCF study (per Annex III). Additionally, a PMCF study is needed for Class III and implants that have relied on equivalence in order not to perform clinical investigations, under the MDR (Art 61(4)). A PMCF Evaluation Report should be created for all PMCF studies, and its information should be utilized to update the CER throughout the lifetime of the device. Many medical device manufacturers have not yet caught up with these requirements and we often find in performing such gap analyses that the PMS/PMCF plans (and hence reports) either do not exist or have major deficiencies to these new requirements.
A list of common gaps in technical documentation (Design Dossiers/Technical Files) include:
1. Additional details required under MDR, such as: additional information for manufacturing and supplier steps, full analysis and results of testing summarized in the technical file and full descriptions on device compatibility and/or accessories to the medical device.
2. The format of the Technical Files and Declarations of Conformity must be updated according to the MDR (including Annex I, II, III and IV). We offer training in 'How to write a Technical File', please keep an eye on our events calendar.
3. The Essential Requirements checklist is to be updated to MDR (Safety and Performance Requirements Checklist), with special attention to be paid to:
a. GSPR 13.1 and 13.2 respectively, regarding additional requirements for devices that may contain derivatives of animal origin.
b. Instructions for Use (IFUs) and labeling should be updated to conform to GSPR 23. Additionally, EU-UDI requirements must be incorporated in both the Technical Documentation as well as the labeling/IFU.
c. GSPR 10.4 on Hazardous Substances is especially noted, as it is now requiring extensive justification in regard to potential patient or user exposure to the/any Carcinogenic, Mutagenic or toxic to Reproduction (CMR substances) or endocrine-disruptor substances in certain devices.
As it can be seen, a variety of elements from the MDR and MEDDEV 2.7/1 Rev. 4 now require additional attention from medical device manufacturers, among many others.
Please keep an eye on our website, we will have an updated blog later on with MORE learnings from the gap analyses we do.
For any specific questions, you may have regarding your device’s compliance to the new regulations, feel free to reach out below at: 0031 (0)20 78 82 630 or send a mail to info@qservegroup.com
Adriana