The Clinical Evaluation Report Bringing it Together

1. The Clinical Evaluation Report: Bringing it Together If you are in Medical Device field, CER is one of the important bases of your business and with progress of time lot of new requirement and addition to old compliance status have changed. With MDR coming in picture lot of new challenges have emerged to those who are in business of medical device since long but have not kept aligned with these developments and somehow trying to manage hard way to comply as they understand which can collapse anytime if any untoward things may happen. Writing and compiling of CER in many such manufacturers are done when device is ready for market. They just consider one of the legal document formalities like other documents needed. This is not the right approach. The scenario was completely different before 1993, when importance to clinical efficacy and safety was given as focus was on manufacturing and product quality. In 1993 came new EU directive and later with many amendments MEDDEV guidelines (latest MEDDEV 2.7/1 rev4, 2016) were released. This is latest and being used as good guidance document. Later in 2017 MDR was published which brought some additional requirement. Now you understand why the CER become so important document which can impact business. If flaws are found by notified bodies, you have no other way but to comply which means delay and spend more for making it fast. Suggested approach: Now ISO as well as MDR suggests for strong quality system for medical device manufacturer. Infect, annex IX of MDR requires that manufacturer should submit a documentation as part of quality management system. This includes procedures for doing activities required which are guiding steps for building technical documents and managing various system within organisation. This will be especially useful for CER author as guideline and ready references description makes it easy to refer as latest requirement. CER is live document and its preparation should be started at the beginning of the clinical evaluation process. The guideline 2.7/1 rev 2.4 describes several stages of clinical evaluation. If we pick up exact text from guideline. The clinical evaluation is based on a comprehensive analysis of available pre- and post-market clinical data relevant to the intended purpose of the device in question, including clinical performance data and clinical safety data. There are discrete stages in performing a clinical evaluation: • Stage 0: Define the scope, plan the clinical evaluation (also referred to as scoping and the clinical evaluation plan). • Stage 1: Identify pertinent data. • Stage 2: Appraise each individual data set, in terms of its scientific validity, relevance and weighting. • Stage 3: Analyse the data, whereby conclusions are reached about. Compliance on performance and safety, Information on label and IFU, residual risks, uncertainties, whether some un-answered questions will be acceptable for CE marking or they will be addressed during PMS phase. • Stage 4: Finalise the clinical evaluation report. The clinical evaluation report summarises and draws together the evaluation of all the relevant clinical data documented or referenced in other parts of the technical documentation. The clinical evaluation report and the relevant clinical data constitute the clinical evidence for conformity assessment. This thus states that CER writing is stage 4 process but it contains all stages and hence process must be started at stage 0. Writer should start taking help of all relevant experts. All above stages are described in detail in different sections of this guideline. Data analysis by experts may uncover latest information which

2. may raise new question so scope gets widened which may need refining clinical evaluation plan. It is also recommended that each section should be sent to specific experts and drafts should then be combined in various sections. CER for medical devices is not smooth homogenous continuous document but it contains various preclinical, clinical and technical documents. Author or manufacturer must have plan for review of each document and its compilation. CER information should be such that it should be understood by an independent party which is usually regulatory authority-notified body. They would like to understand available data, analysis done, assumptions made and conclusion reached.Supporting cross references must be presented. If new device or innovative technology is involved, overview of development process is also expected. Notified bodies play significant role in approval of this report. The guideline appendix A12 also describes guideline for Notified bodies. Reviewing this guideline thus helps the team of CER and specifically Author or team leader. Common gaps found in CER: Additional details needed in MDR: Manufacturing and supplier steps, full analysis, results of testing included in technical file, description on device compatibility and/or accessories. Essential requirement checklist is to be updated to MDR (Safety and performance requirement checklist like GSPR (General safety and performance requirement) 13.1 and 13.2. IFU and labelling as per GSPR 23, GSPR 10.4 on hazardous substances like CMR substances (Carcinogenic, mutagenic or toxic to reproduction) CER must also include state of the art (SOTA) of the relevant clinical field and assessment such as unmet clinical need to be met by the device. Since MDR has brought new dimension where Notified Bodies look at the “latter in MDR” for clinical evaluation “to the latter” of MDDEV 2.7-1 rev 4. It is therefore suggested that writer should make direct references to relevant sections in CER. Another important aspect is equivalence if claimed, must be addressed properly. Such devices CER needs to review the evidence and provide the argument to justify the claimed equivalence. MDR includes more detailed discussion on equivalence apart from guideline MDDEV 2.7-1 rev 4. If any difference exists between the device and device in equivalence must be highlighted. For all such needs it is also recommended to take the help of CER consultants who can give various viewpoints on similar devices in the market. Those manufacturers who are not familiar with compilation of all sections of CER, must seek help from medical writer or CER consultants.