IVDR and MDR

What are medical devices?

A medical device is an instrument, apparatus, device, machine, appliance, implant, reagent for in vitro use, software, material, or similar or related item intended by the manufacturer to be used alone or in combination for a medical purpose.  

What are IVD (in vitro diagnostic) products?

Diagnosis is the first step to effective treatment and the first protection against the spread of many diseases. In vitro diagnostics are clinical tests that analyze samples taken from the human body. They help cure, treat or prevent diseases.

These tests include laboratory-based tests, in which samples are sent to a central laboratory for analysis, point-of-care tests, which can be performed near or at the site of patient care, and tests that consumers can use at home.

Ellecom works with an experienced team dedicated to compliance and regulatory issues in the MDR market and the IVD market, and always keeps abreast of new trends and requirements in the medical device and IVD market.

The changing regulatory framework created by the implementation of the EU Medical Devices Regulation (2017/745) and the EU In Vitro Medical Devices Regulation (2017/746) is impacting how medical devices and IVDs are reclassified and, if necessary, upscaled.

Companies with knowledge and experience of regulatory issues will find it easier to ensure a smooth transition.

Over the years, Ellecom has established sustainable business relationships with various competent authorities, notified bodies, clinical laboratories and think tanks. The company is also working on a dynamic, evolving and efficient post-market surveillance system. The knowledge and network-based methodology provide Ellecom with a competitive advantage in the market and the ability to serve the price-sensitive medical device and IVD market.

Since its inception, Ellecom has worked with manufacturers specializing in the production of in vitro diagnostics and other medical devices and understands the market for these products. Ellecom, with its product and regulatory knowledge and experience, provides its customers with services related to the mandatory requirements needed to place goods on the European market for the first time, such as clinical validations, CE certifications, product registrations, etc. In addition to the legal and regulatory requirements, it also offers customized services to its customers.

In the European Union, the European Medical Device Regulation (MDR) has governed the legal framework for medical devices and their accessories since May 2017. It became fully applicable in May 2021.

The regulatory requirements of the MDR demand the documentation of the complete product life cycle of a medical device. This product life cycle begins with the manufacturer's impulse to develop a product or a product idea and ends only after the medical device has been withdrawn from the market by the manufacturer.

The MDR requires, among other things, the performance of a conformity assessment procedure and contains rules regarding the placing of medical devices on the market. Placing on the market means that the manufacturer makes the medical device available for the first time.

Furthermore, the MDR also contains the following aspects: a new classification system (classes I, IIa, IIb and III) and corresponding classification rules, increased requirements for traceability of medical devices - for this purpose the Unique Device Identification (UDI) was established. In addition, requirements for Notified Bodies were specified and rules for the evaluation of software as a medical device were established. Moreover, additional focus was placed on the various players and their responsibilities.

Since the introduction of Regulation 2017/746 on in vitro diagnostic medical devices (IVDR), a classification system has also been in place for in vitro diagnostic medical devices, which, among other things, influences the choice of conformity assessment procedure and determins the scope of the performance assessment.

The following criteria, among others, are considered in the classification: the invasiveness and presence of an energy source, the duration of use, and the intended use.

Classification also influences the placing on the market as well as post-market surveillance. Finally, the classification determines which requirements regarding surveillance and notification obligations the medical device manufacturer must comply with. To put it simply, a higher class also requires a higher monitoring effort.

Risk management for medical devices is regulated in the EN ISO 14971:2019 standard. Risk management is an elementary component of quality management. It shows how the assessment and control of risks are to be implemented throughout the entire product life cycle of a medical device. The focus here is on the testing and estimation of damage; in particular, the severity and probabilities of damage must be evaluated as correctly as possible as part of the risk assessment. 

A first sub-step of risk management is risk analysis. This in turn requires documenting the results in the risk management file. Data from clinical follow-up can be used to further fine-tune this.

As part of risk management, risk control measures must be decided upon and implemented. If a residual risk cannot be adequately reduced by risk control measures, the manufacturer must determine whether the benefit of the intended use outweighs this residual risk. Thus, the benefit-risk analysis must be reassessed in this setting.

Medical device manufacturers can use the requirements as an opportunity to respond appropriately with their products to changing requirements or framework conditions, in particular through the benefit-risk analysis and the overall residual risk assessment. It is clear that the application or use of a medical device always involves a certain risk and that certain residual risks can never be completely eliminated.

The medical device manufacturer has the responsibility to actively collect and review relevant information about the medical device during manufacturing and downstream manufacturing phases. The manufacturer must identify and take action in two distinct areas: first, with respect to the medical device itself, and second, with respect to the risk management process. Of course, the documentation in the risk management file must not be missing.

Ellecom supports manufacturers in developing risk management processes and integrating these processes and documents into the technical documentation.

To demonstrate that the medical device meets the essential safety and performance requirements, a clinical evaluation must be performed. The demonstration of the essential safety and performance requirements requires the specification of the safety and efficacy of the medical device as well as an acceptable benefit-risk ratio. For this purpose, the medical state of the art must be taken into account. The basis for this is the intended purpose of the medical device as stated by the manufacturer. The aim is to be able to demonstrate sufficient clinical evidence.

A number of requirements are placed on the clinical evaluation. It must: be objective, i.e., include both positive and negative outcomes; demonstrate appropriateness and proportionality to the medical device in terms of type, risk class, intended purpose, and specific characteristics; and demonstrate the requirements of the essential safety and performance requirements.

The basis for clinical evaluation is the collection, processing and use of clinical data. In doing so, the medical device manufacturer should draw from as wide a range of sources as possible. The following data sources may be considered: clinical trial(s) of the medical device; clinical trial(s) of a similar device; scientific literature; post-market clinical follow-up information.

The clinical evaluation is the basis for subsequent post-marketing clinical follow-up.

For the clinical evaluation of medical software, MDCG has issued a separate guideline (MDCG 2020-1). The general process or elements for clinical evaluation are identical to other medical devices, i.e., after a clinical evaluation plan is created, clinical data is identified, evaluated and analyzed, a clinical evaluation report is written, and updates follow through post-market clinical follow-up (PMCF). The difference lies in the demonstration of clinical, technical, and analytical performance and clinical utility.

Validation of technical performance and analytical performance is accomplished by demonstrating the ability of the medical software to accurately, reliably, and precisely produce the intended output from the input data. Evidence is provided, for example, through unit-level testing, integration testing, and system testing, or through the generation of new through the use of databases, registries, reference databases, or the use of previously collected patient data.

Validation of clinical performance is accomplished by demonstrating the ability of medical software to provide clinically relevant results in accordance with its intended purpose. By testing the medical device software under evaluation or an equivalent product in the target population and for the intended use, e.g., preclinical testing, a clinical investigation, or a clinical performance study, evidence of clinical performance can be provided.

Post Market Surveillance (PMS) is intended to increase patient safety by proactively identifying problems or incidents related to the medical device and reporting them to the competent authorities, Notified Bodies, economic operators and/or users. The performance of the medical device in the market is monitored for this purpose. For each device or family of devices, the manufacturer should define an appropriate strategy for placing the device on the market.

Risk and incident reporting requires the manufacturer to respond appropriately to reportable incidents and to communicate trends. Where necessary, the manufacturer must determine and implement preventive actions, corrective actions, and/or corrections and document them in the Periodic Safety Update Report (PSUR). For this purpose, the manufacturer must set up a system with which this monitoring can be ensured and the collected data can be evaluated effectively and appropriately.

If the manufacturer detects a serious incident, he must initiate a safety corrective action in the field. This is accompanied by an obligation to report the incident without delay. A prerequisite is that a causal relationship has been established between the incident and the medical device. Regardless of the form chosen, the manufacturer must ensure that every complaint is taken into account. The affected users must be informed of the measures taken by the manufacturer as part of the field safety corrective action through what is known as a field safety instruction. This field instruction must be worded in the same way in all EU countries and must be available in the respective national language.

In addition, the manufacturer shall prepare a risk-benefit assessment for each medical device or group of medical devices. This assessment must necessarily be updated regularly according to the collected data and information from post-market surveillance and adapted where necessary. The medical device being evaluated must not endanger the patient, the user, or third parties. The aim is that the measured risks can be assessed as acceptable, measured against the benefit to the patient.

The quality management system DIN EN ISO 13485:2016 is the QM system relevant for medical device manufacturers and is harmonized with the MDR. ISO 13485 certification is a necessary step for the manufacturer on the way to successful conformity assessment.

Obtaining ISO 13485 certification is not equivalent to meeting all MDR or IVDR requirements. Only the aspect of QM system requirements can be certified through ISO 13485 certification. Thus, ISO 13485 provides a strong basis for establishing a QM system that is compliant for medical devices or IVD products.

Often, compliance with the QM system requirements in ISO 13485 can be achieved by implementing the MDR: ISO 13485 refers to compliance with regulatory requirements, in the form of laws or regulations. For example, in section 7.5.9 of ISO 13485 on the aspect of traceability, reference is made to the fact that the traceability of the medical device must comply with the regulatory requirements. Since the assignment of the UDI is a requirement of the MDR, it is thus also automatically a requirement of ISO 13485, even if the UDI is not explicitly mentioned there.