Launching a new medical device in the market always need a Clinical Evaluation Report to submit to the EU Market as per the European Union’s Medical Device Regulation (MDR) introduced in May 2017. Based on the device’s risk category, the Clinical Evaluation Report can be simple or quite extensive. CER is a major portion of the technical file even though it is a stand-alone document and is required for all medical devices regardless of classification. The more at the stake, a more detailed significant report is mandatory for a device. Manufacturers will need to generate and provide more in-depth clinical data to prove safety and performance claims including tighter equivalency standards. In-spite of number of resources required to complete the medical device CER, the structure of a CER will always be same. Many companies face difficulty in understanding the MDR regulations section which defines the medical device clinical evaluation report requirements. In the present content below, you can see the answers to many questions that are revolving gin your mind before starting anew CER for the medical device to enter into EU market. With the pertinent details provided here, you also can plan ahead and commit accurate enough resources for efficient completion.
Six Needy Things to Mind for CER
A composite analysis of pre and post market surveillance to verify safety, and performance of a medical device must be embedded in clinical evaluation report, which in-turn must back the medical device to get an approval and sale in European market. The CER should include, a clinical evaluation which is an ongoing structured procedure to collect, appraise, and analyze clinical data related to safety and performance of that specific device. Need to assess if the available clinical data is enough to confirm compliance with appropriate essential requirements for safety and performance, when using the device as per the manufacturer’s instructions. A five distinct stage procedure (Stage 0, 1, 2, 3 and 4)need to be followed to perform clinical evaluation for medical device manufacturer.
Stage 0: Scope and plan
At this stage, design a plan to perform clinical evaluation, find the scope of medical device and clinical evaluation report.
Stage 1: Identification of pertinent data
Once the scope is defined, identify the existing pre and post market clinical data which was documented from clinical trials, data generated from risk analysis, preexisting literature, and clinical experience.
Stage 2: Appraisal of pertinent data
Evaluate and appraise each data set that shall be used for scientific validity, and for clinical evaluation relevance, which will add weight to the final report.
Stage 3: Analysis of clinical data
Data analysis should contain Benefit/ Risk Profile, Residual Risks, and Uncertainties/Unanswered Questions. As a part of medical device’s Essential Requirements/General Safety and Performance Requirements – safety and performance of it must be determined at this stage. This provides strength to overall evidence.
Stage 4: Finalize the Report
Clinical evaluation should be prepared strongly with the clinical evidence for conformity assessment. With a thorough summary of the data analysis report, medical device can be approved for trading in the EU market.
All the medical device manufacturers must submit this CER in EU market for approvals from regulatory bodies. Similarly, if the device wants to release in other country markets; respective local reporting requirements should be submitted as per their guidelines. For instance, if to release in USA, premarket approval (PMA) annual reports of that particular medical device has to be submitted to the US FDA. If any information regarding medical device has an important bearing on the benefit-risk assessment, that may indicate a need for labelling changes regarding contraindications, warnings, precautions or instructions for use etc. These needs should be communicated by the manufacturer to the local regulatory bodies in accordance with local reporting requirements. Every medical device manufacturer must satisfy the Quality Management System (QMS) guidelines by implementing and maintaining surveillance programs which mainly focuses on safety, clinical performance and/or effectiveness of the device.
CER: To start with..!
What important information has to pen down in the CER and the steps to follow?
CER document is the report with a proper clinical investigation in accordance with the local regulations without any risk to the user and to get approvals from regulatory bodies. The lead role of a medical devices CER is to collect, assimilate and present the data objectively as discussed in CEP. No matter the type of the device that is going to launch, the architecture of an effective CER is with six indications as per the MEDDEV 2.7/1 Rev. 4/EU MDR. These sections information will come from many sources like manufacturers, quality specialists for complaint data, librarians, safety specialists and scientists. Below are the detailed six proposed table of contents for a robust CER.
1. Summary of an overall CER
Though the summary is the first section to read; yet this is the section to be written at the end. It should give succinct overview of clinical condition and state of the art; brief details of the subject device and its indication; conclusions of the evaluation pre-clinical studies, pre-market clinical investigations, risk management, post market surveillance ,and published literature; risk-benefit profile conclusion. Summary often can be closed in two pages length by concluding the aforementioned clinical investigations.
2. Scope of the clinical evaluation
The scope defines the objectives of the CER, guidelines &standards to follow, references that were chosen to report in CER evaluation. Objectives are to support device conformity with safety and performance Essential Requirements as per the EU MDD 2007/47/EC, which is to be superseded by the Medical Devices Regulations’ (MDRs’) General Safety and Performance Requirements. Scope should also state whether the CER is in support of initial CE-marking, or a CE mark renewal, or is at the request of the Notified Body(NB). The documents & additional documents required for CERs, CE marked or new devices and equivalence with another device are being claimed are listed here
Before CE Marking: Equivalence data if claimed.
All CERs: Device description, design features, intended purpose, warnings, contraindications as per IFU, risk management documents, current knowledge/state of the art, data sources like in-house reports and, published literature.
CE MARKED DEVICES:> Relevant changes in design, materials, IFU, newly emerged clinical concerns, PMS new data, PMS Plan, PSURs, PMCF Plan and PMCF study data if
Apart from MEDDEV 2.7/1/EU MDR suggested documents, guidance documents are
- EN ISO 14155:2020 – Clinical Investigation of Medical Devices for Human Subjects -Good Clinical Practice
- EN ISO 14971:2019 – Medical Devices –Application of Risk Management to Medical Devices
- EN ISO ISO 10993:2020 – Biological evaluation of medical devices
- EN ISO 13485:2016 – Medical devices — Quality management systems — Requirements for regulatory purposes
- EN ISO 11607:2019 – Packaging for terminally sterilized medical devices. Requirements for materials, sterile barrier systems and packaging systems
- EN ISO 11737:2018 (+A1:2021)and EN ISO 11135: 2014 (+A1:2019) – Sterilization of health care products
- EN ISO 15223-1:2021 – Medical devices — Symbols to be used with information to be supplied by the manufacturer — Part 1: General requirements
- EN ISO 20417:2021 and EN 1041:2008+A1:2013 – Information supplied by the manufacturer of medical devices
- MEDDEV 2.12/2 rev2 Post Market Clinical Follow-up – A guide for manufacturers and Notified Bodies (January 2012; to be superseded by MDR Annex XIV)
- NB Med 2.12 Rec1 – Post Marketing Surveillance (February 2000; to be superseded by MDR Annex III).
Also MEDDEV 2.1/6 or EU MDR, Annex VIII, Chapter III, section 6.3 – Quantification and Classification of Stand Alone Software (January 2012),should follow for a devise based on its type. Reference materials used in preparing the CER include the IFU, literature review, clinical investigation reports, risk management reports, PMS reports.
3. Clinical Background
This section needs heavy research with literature search, appraising the data subjecting to device, and with recent time frame .State of the Art (SOTA) role with current knowledge became very important from MEDDEV 2.1/7 rev. 4 introduction. An overview of a literature review should be provided to the authors to give an idea about SOTA of device being reviewed. This clinical framework should address the details of systematic review databases, search terms and methods, literature review selection criteria, quality control measures, results, number and types of literature research. Always the SOTA bibliography must be separated from literature review bibliography even if there is overlap among the data. Additionally, clinical background data sources description should be mentioned, this section also must discuss about the necessary standards, guidance, competitor products, and equivalent devices. This section also must focus on explaining how the device fits into SOTA medical care setting. Need to describe the condition to be treated, provide epidemiological data with the frequency of disease conditions, explain how the disease is classified and managed, justify the choice of clinical endpoints and identify potential clinical hazards. Also provide the available insights for treating the condition, delve the risks and benefits of the available treatment options, and explain who would be using the device in clinical setting. For some medical devices which are used for few minutes like dental nipper require a short clinical background and pin point description is sufficient. Whereas a device used to treat complex medical condition need a strong clinical background with critical evaluation.
4. Device under evaluation
This particular section includes medical device description for approval with appropriate details to assess compliance with Essential Requirements/General Safety and Performance Requirements. All details should be included with device photographs, diagrams, usability testing data, methods used for the CER, and data analysis. If the device is marketing based on being equivalent to another device, its functional equivalence must be validated based on technical, biological and clinical characteristics as well as pre-clinical studies, risk management, pre-market clinical investigations and post-market surveillance. Under clinical condition device must be equivalent with comparable device based on its same clinical condition, same medical indication, same intended purpose, same site in the body, similar population relevant to critical performances such as duration of use, specific clinical effects, etc. When the compliance come to technically similar, it should be satisfied in similar design, similar conditions of use, similar specifications and properties e.g. physicochemical properties, similar deployment methods, and similar principles of operation and critical performance requirements with comparable device. Biological similarity should be, the device must use similar materials or substances coming in contact with the same human tissues or body fluids and duration of time in contact. The final important segment of this section to be presented in CER is clinical literature review, which can take as much time to write with elaborated, accurate justification of the conformity assessment with regard to device and patient related risks. This section should be more emphasized on a quality assessment of the available evidence from the literature and on the scientific validity of the literature reviews itself.
This section gives a brief description about the device compliance with Essential Requirements/General Safety and Performance Requirements for patient safety and device performance claims, either therapeutic or diagnostic, with a concise technical and physical description of the device based on the clinical evidence presented. A gist of the benefit/risk profile; clinical evaluation and SOTA should be explained. This section should also focus on compliance statement such as adequacy of manufacturer information materials, intended purpose/risk reduction guidance, and device suitability for intended users. A brief note on clinical data analysis reports with the manufacturer’s safety claims, information materials, and the clinical-state-of-the-art for treating the intended condition should be stated. Also, residual risks or unanswered questions if any should be addressed. In case, if the retrieved clinical data analysis is not able to conclude or any residual risks are found, the conclusion can be given on ongoing research and safety activities.
6. Dates, references and next clinical evaluation date
This is the final section to be closed with CER that should include date of succeeding clinical evaluation, current clinical evaluation date, evaluators signed statement, manufacturers final release date, qualifications of the evaluators, and references that are included in the text in proposed format. CER updates are coordinated with the notified body audit and certification renewal process which can vary from one to five years based on the risk source of the medical device.
Importance of CER
Preparing and submitting of the CER document is not an optional part of marketing a medical device; it is the most crucial part of the CE technical file with safety and performance of device under approval. The clinical evaluation report is a key component of the CE Marking process. To market a device in European Union, clinical evaluation report is needed. EUMDR emphasizes on the importance of the CER and include general safety and performance requirements, clinical evaluation review and documentation. It is always good to have a CER as stand alone document to make the update process easy on regular basis as per the agreement with notified bodies. Efforts and length to prepare a CER vary significantly depending on the number of factors such as length and duration of the device in contact with patients, risk analysis, etc. CER will be a less complicated document if provided with strong case for equivalency in place of clinical data analysis. The most important thing to remember is – at any circumstances if fail to complete/update CER, it will put your medical device at risk, so it is mandatory to consider this critical function very seriously with all the aforementioned six detailed sections.