10 Important Tips When Writing a Clinical Evaluation Report (CER) for Medical Devices

writing clinical evaluation reports, CERs, clinical reports, scientists sanctuary

A clinical evaluation report (CER) is a vital document that combines both pre-market and post-market clinical data of a medical device. The CER should provide essential information on the safety, performance, and clinical benefit and is a requirement for medical device manufacturers to show they meet regulatory compliance and that their devices are safe and effective for use by patients. Writing a CER can be a complex task but following these 10 important tips can help ensure that the report is comprehensive, accurate, and meets all the necessary requirements.

1. Define a CER protocol and scope

A CER should have a clearly defined scope. This should include addressing the intended use of the device, clinical indications and the patient population. This information will help ensure that the CER is focused and relevant. The Medical Device Coordination Group (MDCG) published a Clinical Evaluation Assessment Report Template (MDCG 2020-13) in July 2020. This template is meant to aid medical device manufacturers when constructing their CER and aid Notified Bodies when assessing the conclusions. It’s also important to remember that the template presents the minimum content that is required for a CER. Additional guidance documentation as well the regulation will help construct a more thorough report.

2. Conduct a thorough literature review

The literature review forms one of the critical components of the CER and should be conducted using a systematic approach. The review should include all relevant clinical studies, published articles, and other relevant data sources. Literature databases such as PubMed, Embase and ClinicalTrial.gov should be used (although don’t limit your search to these only). As a rule of thumb, try to use at least three different literature databases that cover data from various territories.

3. Understand the regulatory requirements

It’s important to understand the regulatory requirements for the medical device in question and in relation to the target market / territory in which it is being sold. Ideally your CER should go hand in hand with additional documentation that identifies and addresses the safety and performance requirements which show that the device is safe for use and performs as intended. For Europe, this would be your GSPR document.

4. Ensure you conduct a thorough, systematic evaluation of the clinical data

The clinical data should be evaluated using a robust and transparent methodology. Data should be analyzed, synthesized, and presented in a clear and concise manner. The best way to determine an appropriate analysis method would be to use the guidance documents that have been made available to you. This includes the MEDDEV and MDCG guidelines as well as the use of any international / harmonized standards.

5. Consider all available data objectively

When evaluating the clinical data, it is important to consider all available data sources in an objective way. This includes data from post-market surveillance, post market clinical follow ups, adverse event reports, literature searches, risk analyses and clinical studies. A CER should identify and address all safety and performance issues associated with the medical device including potential risks and hazards, as well as any complications that have been reported. All relevant data should be evaluated and included so as to present a complete picture around safety and performance.

6. Demonstrate equivalence

Equivalence is an important part of showing that your device is safe and performs as intended. To show equivalence, manufacturers are required to compare their medical device to another pre-existing device that has similarity and which has already been CE-marked. Similarity can be shown by comparing critical characteristics such as chemical, biological and technical parameters.

7. Ensure the report is well-structured

The CER should be well-structured with clear headings and subheadings. This will help readers navigate the report easily and find the information they need quickly and easily. Use clear and concise language. Any technical terms and complicated scientific concepts should be explained so as to avoid any questions later on. The report should be written in a style that is easy to understand for anyone reading it – this could be a clinical expert to a distributor to an end user.

8. Use visual aids to enhance understanding

Visual aids are extremely important when writing a CER as it helps enhance the understanding of complex data and clinical concepts. These visual aids can include tables, graphs and diagrams. Ensure they are appropriate and support the text.

9. Ensure the report is up-to-date

The CER should be kept up to date with the latest clinical data, market trends, and regulatory requirements. This means that it should be updated periodically to present the latest snapshot of your device clinically. An update could be triggered when there are reported adverse events, changes to any warnings or contra-indications and when post-market clinical data becomes available. This will help ensure that the report remains relevant and useful over time.

10. Highlight the benefit to risk data of your device

One of the recent requirements for medical devices is to compile a benefit-risk report which highlights quantifiable acceptance criteria around safety and performance of the device in question. This requires detail around specifying criteria used to determine acceptability of the benefit-risk ratio which in turn supports the conclusion that the device is safe, performs as intended and should be placed on the market. Ideally this data should also be highlighted in the CER and the manufacturer should show that there are more benefits than risks associated with the device.

Writing a clinical evaluation report for medical devices requires careful planning, thorough research, and attention to detail. These 10 essential tips are a start to compiling a comprehensive and accurate CER. The Medical Device Regulations and various guidance documents form an essential base from which to start when ensuring all necessary requirements for regulatory compliance are met however, despite engaging all of these documents, manufacturers can never really predict what gaps a Notified Body will pick up after review. It’s also important to treat the feedback from your Notified Body as constructive with the main goal of portraying all available information that shows the medical device in question performs as intended with the ultimate goal of putting the safety of patients first. 

How To Classify Your Medical Device Under the EU MDR 2017/745

Did you know that under the EU MDR 2017/745, you now have to reclassify your medical device… even though it was previously classified under the old Medical Device Directive (MDD 93/42/EEC)?

If you want to learn about classifying your medical device, then you’ve come to the right place! In this post we’ll be looking at the different risk classes of medical devices, how to classify your medical device under the EU MDR 2017/745 and I’ll be sharing with you a simple gap assessment tool that can help you determine what your new classification will be.

Classification of Medical Devices, EU MDR 2017/745, medical device classification

What is the MDR and how are the different risk classes defined?

In Europe, medical devices are regulated by the European Commission. The Regulation that is currently being used to regulate medical devices is the European Union Medical Device Regulation 2017/745, or as it is more commonly referred to, the EU MDR 2017/745 or simply, the MDR.

This regulation now supersedes the Medical Device Directive 93/42/EEC.

In order to obtain a CE mark for a particular medical device, a conformity assessment will need to be conducted. This is usually based on the risk class of the medical device in question.

What are the categories of medical devices?

The EU MDR has 4 main categories when it comes to medical device classification. These are Class I, IIa, IIb and III.

The duration of use and overall definition of the medical device is also important when determining the risk class.

As a start, the duration of use can be broken down into three main groups:

  • ‘Transient’ – this means normally intended for continuous use for less than 60 minutes
  • ‘Short term’ – this means normally intended for continuous use for between 60 minutes and 30 days
  • ‘Long term’ – this means normally intended for continuous use for more than 30 days

These groups of ‘duration of use’ remain the same as the previous Medical Device Directive 93/42/EEC.

Each class of medical device is ranked from the lowest risk (class I) to the highest risk (Class III) with each risk class requiring a different conformity assessment route. This means that depending on your risk class, there be a different defined set of steps that needs to be followed in order to obtain a CE mark.

Now let’s look at the classes in more detail.

Class I

Class I medical devices are known as those devices with the lowest risk. Common examples include bandages and glasses. In these cases, manufacturers can self-certify their devices without the involvement of a notified body.

Class I medical devices are then further broken down into three sub-classifications:

  • Class Is: The medical device must be presented sterile 
  • Class Im: The medical device has a measuring feature 
  • Class Ir: The medical device is a reusable surgical instrument

Class IIa medical devices

Class IIa medical devices are considered medium-risk devices. Common examples include hearing aids and catheters. Unlike Class I devices, the manufacturer must receive approval from a notified body.

Class IIb medical devices

These medical devices are considered to be medium to high-risk devices. Common examples include ventilators and insulin pens. These devices also require the involvement of a notified body to obtain their CE mark.

Class III medical devices

Class III medical devices are considered the highest risk medical devices. These devices often have more regulatory requirements associated with them before obtaining a CE mark such as having a clinical investigation plan and clinical evaluation report. Common examples of class III medical devices include pacemakers and breast implants.

How do you classify your medical device under the EU MDR 2017/745?

The MDR uses a rule-based system for classifying medical devices. These rules are defined in Annex VIII of the MDR 2017/745.

This annex includes 22 rules for classifying medical devices.

The rules are divided into four sections, and the rules of each section apply to a specific category of devices. The rules are set out as follows:

  • Rule 1– Non-invasive devices
  • Rule 2 – Non-invasive devices intended for channeling or storing
  • Rule 3 – Non-invasive devices that modify biological or chemical composition of blood, body liquids, other liquids and cells
  • Rule 4 – Non-invasive devices in contact with injured skin or mucous membrane
  • Rule 5 – Devices invasive in body orifices
  • Rule 6 – Surgically invasive devices for transient use
  • Rule 7 – Surgically invasive devices for short term use
  • Rule 8 – Surgically invasive devices for long term use and implantable
  • Rule 9 – Active therapeutic devices intended to exchange or administer energy
  • Rule 10 – Active devices for diagnosis & monitoring, emit ionizing radiation
  • Rule 11 – Software intended to provide information which is used to take decisions with diagnosis or therapeutic purposes (from class I to class III)
  • Rule 12 – Active devices intended to administer and/or remove medicinal products, body liquids or other substances
  • Rule 13 – All other active devices
  • Rule 14 – Devices incorporating a medicinal substance including human blood or plasma
  • Rule 15 – Contraception or prevention of the transmission of sexually transmitted diseases
  • Rule 16 – Specific disinfecting, cleaning and rinsing devices
  • Rule 17 – Devices specifically intended for recording of diagnostic images generated by X-ray radiation
  • Rule 18 – Devices utilizing non-viable tissues or cells of human origin or tissues of animal or derivatives

There are also four new rules:

  • Rule 19 – Devices incorporating or consisting of nanomaterial
  • Rule 20 – Invasive devices with respect to body orifices to administer medicinal products by inhalation
  • Rule 21 – Substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed
  • Rule 22 – Active therapeutic devices with an integrated or incorporated diagnostic function which significantly determines the patient management

The duration of the device’s use is used to determine which rule(s) apply within a given category. The three types of duration specified in the MDR are:

So how do you actually classify your medical device?

To classify your medical device, follow these three critical steps:

STEP 1: Determine which definition your medical device falls under according to the definitions defined in the MDR 2017/745.

STEP 2: Determine which rule applies to your medical device. If there are multiple rules that are applicable, then choose the rule with the highest risk.

STEP 3: Document the applicable rule and justification. This can be done in a simple classification document.

What if my device is a borderline medical device?

If your product is a borderline product (i.e. a mix between a drug and a device), you will need to identify the main intended use before classifying your device as either a medicine or medical device. Then follow the relevant classification rules.

To help you classify your medical device, I’ve created a simple classification gap assessment document. This document breaks down the classification rules clause by clause so you can determine if a particular definition is applicable to your device.

This way, you can easily determine how your device is defined according to the EU MDR 2017/745 and which is the applicable classification rule.

Download the free classification gap assessment here.

How to Comply with the General Safety and Performance Requirements (GSPR)

In today’s post we’re talking about the General Safety and Performance Requirements (GSPR) under the new European Medical Device Regulation (MDR 2017/745) and In Vitro Diagnostic Regulation (IVDR 2017/746). If you are a manufacturer trying to transition to the new MDR 2017/745 or IVDR 2017/746 or even just trying to get a CE mark for the very first time, then being able to show how your device complies to the new General Safety and Performance Requirements is critical.

What is the GSPR?

The GSPR stands for General Safety and Performance Requirements and forms part of Annex I of the new European Medical Device Regulations: MDR 2017/745 and In Vitro Diagnostic Regulations: IVDR 2017/746.

Manufacturers who want to sell their products in Europe with a CE mark affixed to it will have to show that their device complies with these safety and performance requirements together with being able to provide sufficient evidence that shows how device conformity is maintained. Alternatively, if there are certain clauses of the GSPR that are not applicable to the medical device in question, manufacturers will have to then justify why these clauses are not applicable with sufficient reasoning.

How is the General Safety and Performance Requirements different from the Essential Requirements?

The GSPR now replaces the old Essential Requirements which formed part of the MDD 93/42/EEC. The Essential Requirements were previously defined as those requirements that every medical device had to fulfill. These Essential Requirements were described by the old Medical Device Directives: MDD 93/42/EEC and In Vitro Diagnostic Directive: IVDD 98/79/EEC. These Directives are now repealed.

As a start, the GSPR now has 23 requirements under the MDR 2017/745 and 20 requirements under the IVDR 2017/746 which is significantly more requirements than the old Directives.

 For indication purposes, the Essential Requirements from the old Directives were broken down as follows:

EU MDD 93/42/EECEU IVDD 98/79/EEC
Chapter 1 – General requirements (clause 1 to 6)Chapter 1 –General requirements (clause 1 to 5)
Chapter 2 -Design and Manuf. (from clause 7 to 13)Chapter 2 -Performance, Design and Manuf. (clause 1 to 8)

Now let’s break down the GSPR:

The GSPR consists of three chapters under the MDR 2017/745 and IVDR 2017/746:

ChapterMDR 2017/745IVDR 2017/746
IGeneral requirements (Clause 1 – 9)General requirements (Clause 1 – 8)
IIRequirements Regarding Design and Manufacture (Clause 10 – 22)Requirements Regarding Performance, Design and Manufacture (Clause 9 – 19)
IIIRequirements Regarding The Information Supplied With The Device (clause 23)Requirements Regarding Information Supplied With The Device (clause 20)

From the tables above, we can see that the Essential Requirements are divided into 2 chapters with 13 items while the new Medical Device Regulations and In Vitro Diagnostic Regulations have 3 chapters with 23 items and 20 items respectively. This means that the scope of details in the safety and performance requirements have increased quite a bit.

Furthermore, several new topics are incorporated in the requirements list of the GSPR. These include (but are not limited to):

  • Requirements for devices that administer or contain drugs
  • Specific requirements for devices that contain tissues of human or animal origin
  • Requirements for disposal
  • Requirements for IT safety
  • Requirements for devices for use by lay persons
  • General requirements for labelling

What does each Chapter of the GSPR require?

Chapter 1: General Requirements

Chapter 1 of the GSPR has many similarities with the old Directives however there is now an increased focus on usability, state of the art and risk management.

Chapter I contains general requirements that are applicable to all medical devices and this includes:

  • Intended purpose, safety of patients, users and other persons
  • Reduction of risks
  • Risk management system
  • Risk control measures
  • Risks related to use error
  • Device performance shall not be adversely affected
  • Device design, manufacture, packaging
  • Risk reduction, acceptable risk-benefit ratio
  • General safety requirements for devices without an intended medical purpose as described in in annex XVI

Chapter II: Requirements Regarding Design and Manufacture

Chapter II deals with the chemical, physical and biological properties of the medical device, together with requirements for infection, microbial contamination and related sterility as well as substances, interactions with the environment and mechanical and thermal risks. These requirements include:

  • Chemical, physical and biological properties
  • Infection and microbial contamination
  • Devices incorporating a substance considered to be a medicinal product and devices that are composed of substances/substance combinations that are absorbed by or locally dispersed in the human body
  • Devices incorporating materials of biological origin
  • Construction of devices and interaction with their environment
  • Devices with a diagnostic and measuring function
  • Protection against radiation
  • Electronic programmable systems – devices that incorporate electronic programmable systems and software that are devices in themselves
  • Active devices and devices connected to them
  • Particular requirements for active implantable devices
  • Protection against mechanical and thermal risks
  • Protection against the risks posed to the patient or user by devices supplying energy or substances
  • Protection against the risks posed by medical devices intended by the manufacturer for use by lay persons

Chapter III: Label and Instructions For Use

Chapter III deals with the requirements around labelling and instructions for use.

This chapter deals with:

  • the format of the instructions for use
  • readability of information
  • how this relates with laypersons and professionals
  • requirements around UDI labeling 
  • labelling for devices that contain human or animal tissue
  • labeling of sterile packaging
  • labelling for devices that contain Carcinogenic Mutagenic and toxic to Reproduction (CMR) substances

How to Create and Complete Your GSPR Documentation

Creating the GSPR has been a difficult step for many medical device manufacturers. Having a starting point can really help.

STEP 1: The first step is to determine what your current state of compliance is. If you are an existing CE mark holder, then you will need to transition your Essential Requirements document to a General Safety and Performance Requirements format. On the other hand, if you are applying for a CE mark for the first time, you will need to create a GSPR checklist from scratch.

STEP 2: Next you will need to perform a Gap Assessment. Start by analyzing the checklist clause by clause. If a requirement is applicable to your medical device, then mark it as applicable.

STEP 3: Next assign the relevant standards and evidence. The applicable standards should be mentioned in your GSPR checklist. Any applicable evidence (such as test reports, technical file chapters, procedures) should also be referenced in specific, concrete detail.

STEP 4: The last step is to add a justification for non-applicable clauses. This is crucial because you cannot just identify a clause as being not applicable without stating a reason why, in relation to your device.

Purchase Your GSPR Checklist here.

Creating a GSPR checklist from scratch can be a nightmare because there are so many clauses to analyze, and you need to document applicable evidence for each clause.

To make the process easier, I’ve created a ready-to-edit GSPR checklist. You can purchase it here.

Buy the template here!