Placing medical devices (MD) and in vitro diagnostic medical devices (IVDs) on the market is not an easy and short path. It takes years until the initial idea finally reaches the market. At AKRN, we often support MD and IVD manufacturers with market access and ad-hoc strategies for each situation. Given our experience, we have prepared a roadmap to illustrate some common milestones that MD and IVD manufacturers should follow to CE marking and enter the EU market.
1. Define the intended purpose
Defining the intended purpose is crucial when planning the road to CE marking. The intended purpose should be a concise statement (two to three sentences) that indicates the use for which the device is intended according to the manufacturer’s information. The definition of the intended purpose will allow the device qualification (section 2) and classification (section 3). Note that the intended purpose must be consistent and present across all product documentation (technical documentation, clinical evaluation, labelling, instructions for use, promotion and sales material).
2. Device qualification and classification
Once the product’s intended purpose is defined, the following steps include its qualification and classification.
The product’s qualification consists of evaluating whether it falls under the EU Medical Device Regulation EU MDR 2017/745 (MDR) or the In vitro diagnostics medical device Regulation EU IVDR 2017/746 (IVDR), respectively. Some products may initially seem to fit the MD or IVD definition, but further assessment can conclude that they are not devices. Examples include medicinal products, personal protective equipment, or lifestyle software without a medical purpose.
By using the applicable regulations, every device is then classified according to its risk. For example, factors such as the degree of invasiveness, the part of the body affected, time in contact with the body and whether or not the device is active are considered when classifying devices. From lower to higher risk, MDs are classified into Class I, Class IIa, Class IIb and Class III, whereas IVDs are divided into Classes A to D. Note that most devices (except MDs Class I and IVDs Class A and B) require the involvement of a notified body to assess the conformity of the device with the above mention regulations.
3. Identification of applicable guidelines, GSPR and standards
Manufacturers of MDs and IVDs have some general guidelines and standards available to support them comply with the general safety and performance requirements (GSPRs) set out in Annex I of the regulations. For example, compliance with ISO 13485 ensures the presence of a solid Quality Management System as required by the MDR and IVDR.
As MDs and IVDs can range from a wide variety of technologies and therapeutic areas with very different requirements, manufacturers should ensure that harmonised standards and international guidelines applicable to the device of interest are used. It is essential to identify these standards early on in the development of the product as some may contain specifications which can impact the design of the product.
Here are some tips to follow:
- Start considering whether the Medical Device Coordination Group (MDCG) or the International Medical Device Regulator Forum (IMDRF) have issued any guidance document that may impact your medical device.
- Identify the General Safety and Performance Requirements (Annex I MDR/IVDR) that apply to your device.
- Identify the key harmonised standards (ISO: International Organization for Standardisation) you apply to your device.
4. Set a quality management system (QMS), and keep it alive!
The establishment and maintenance of a QMS is a key requirement before entering the market. The MDR and IVDR require manufacturers to develop and implement a QMS before placing the device on the market. In fact, this is one of the critical aspects that notified bodies review during the conformity assessment.
Though several parts of the QMS can be addressed in the latest phases of the product development, we recommend implementing a QMS during the design stage. It will save plenty of time for your organisation later on!
Please find more information about the QMS and its related standard, ISO 13485, in the following link.
5. “Design can be art. Design can be simple. That’s why it’s so complicated.”
The product design should be done considering the intended purpose of the device, the user needs and the design requirements. Design should be done following a plan, and there should be processes in place to ensure that both the user needs and design requirements are met (see section 7).
6. Risk assessment
Establishing, implementing, documenting and maintaining a risk management system is one of the obligations of manufacturers according to the regulations. Manufacturers must demonstrate that the device is safe, reducing all the risks associated with its use as far as possible.
Note that when eliminating/reducing the risks, manufacturers should address the following order of priority: (1) safer design; (2) addition of protection measures; and (3) informing about residual risks (warnings/precautions) and/or appropriate training.
Establishing a risk management system is not an easy task. We often see that it is not started until the design is locked, which complicates the risk elimination by safer design. Consider starting in parallel with the device design and use ISO 14971 together with its supportive guidance ISO (ISO/TR 24971) to establish a risk management system compliant with MDR and IVDR requirements.
7. Verification and validation
Once the medical device design has been completed, manufacturers need to test whether the design requirements have been met through verification activities. The device verification activities will confirm whether the design outputs match the initially planned design inputs.
Validation activities, in contrast, will assess whether the device fulfils the intended purpose and the user’s needs. Validation activities are commonly performed through usability studies, pre-clinical studies or clinical investigations. Deciding the appropriate validation tests will depend on many factors, including the type of device and the available clinical evidence for the device (provided by the clinical evaluation report, see section 8).
8. Clinical/Performance Evaluation
A clinical evaluation (performance evaluation for IVDs) is a set of ongoing activities that use scientifically sound methods for the assessment and analysis of data to verify the safety and performance of the device when used as intended by the manufacturer. The clinical/performance evaluation is part of the device validation and determines whether there is sufficient clinical evidence available to support the safety and performance of the device.
Please visit the following links to get more information about clinical and performance evaluations.
9. Clinical investigations and Performance Studies
When the clinical/performance evaluation reveals gaps in the existing clinical evidence, manufacturers may require to conduct a clinical investigation (MDs) or performance studies (IVDs) to fill the gaps.
A clinical investigation is defined as “any systematic investigation/study in/on one or more human subjects” whose main objective is to assess the safety and clinical performance of the device in question and evaluate whether the device is suitable for the purpose and the population for which is intended. In the context of IVDs, performance studies are conducted to establish or confirm the analytical or clinical performance of the device.
ISO 14155 and ISO 20916 provide helpful guidance in designing and executing clinical investigations and performance clinical investigations (IVDs).
10. Technical documentation (TD)
Preparing the TD for a device is a requisite before entering the market. The TD is a compilation of documentation listed in Annexes II and III of the MDR and IVDR to show that the device complies with the applicable General Safety and Performance Requirements (GSPR). The notified body will review the TD as part of the conformity assessment of the device.
11. European and national registries
As part of the requirements set out in the MDR and IVDR, manufacturers shall register their devices in EUDAMED, an IT system established by the MDR and IVDR as a database to improve transparency and coordination of information regarding medical devices available on the EU market. Currently, EUDAMED modules are still under development. Its use will become mandatory for all manufacturers regarding obligations and requirements related to UDI/Device and NB & Certificate modules in Q2 2025.
Meanwhile, until all EUDAMED modules are fully functional, state members rely on their national legislation to register devices and manufacturers.
12. CE marking
The CE mark is every manufacturer’s primary objective. By affixing it to a product (in this particular case, medical devices), a manufacturer declares that it meets all the applicable GSPR and can be sold throughout the EEA. CE-mark can be self-certified or provided after the successful conformity assessment by a notified body (in this case, the CE symbol will be accompanied by four digits that identify the notified body involved in the conformity assessment).
AKRN, your partner for success
AKRN, now part of NAMSA, provides a wide range of quality, regulatory and clinical services to support manufacturers obtain the CE mark for MDs and IVDs. As part of these services, AKRN offers tailor-made CE marking roadmaps, providing the essential information from sections 1 to 12 for a specific product in a detailed report and a Gantt chart including milestones, interdependencies and estimated costs.
Subject Matter Experts
Ariadna Navarro Aragall, Ph.D. Associate Director RA & QA LinkedIn
Albert Negrete Hurtado, Ph.D. Regulatory Affairs Scientist
LinkedIn
