After years in development, the final version of the Medical Device/In Vitro Diagnostic Medical Device Regulations was published in the Official Journal of the European Union on May 5, 2017. These regulations superseded the previous Directives for the European market and will be implemented over the next few years. In our last post, we went over the broad impact of these documents on medical device development and market approval. Here, we’ll zero in on one aspect of market approval that MDR specifically emphasizes: more robust clinical evaluation processes.
What is clinical evaluation?
In the context of medical device market approval, clinical evaluation is the methodologically sound ongoing procedure to collect, appraise, and analyze clinical data pertaining to a medical device. Clinical evaluation also includes analyzing whether or not there is sufficient clinical evidence to confirm compliance with relevant essential requirements for safety and performance when using the device according to the manufacturer’s instructions for use.
What are the sources used in clinical evaluation?
Sources for clinical evaluation can include published data on an equivalent device, clinical investigations, post-marketing surveillance data, public adverse event databases (e.g., FDA’s MAUDE) for equivalent devices, and internal corrective and preventive actions.
A formal Clinical Evaluation Report (CER) is a new requirement under MDR. The CER may prove to serve as the most important tool for providing safety and performance data. This requirement may also act as a trigger for implementing an operationalized approach for device development projects that previously lacked structure.
Why is clinical evaluation required?
In addition to demonstrating a product’s value, clinical evaluation is necessary to receive CE marking, which is required to sell medical devices in the European Economic Area. The EEA is a key market that includes all Member States in the EU, as well as Iceland, Liechtenstein, Norway, Switzerland, and Turkey.
A CER is to be included in the CE technical file as part of the CE marking/conformity assessment process. CER-related services, such as document preparation, are often provided by clinical research organizations like Premier.
How does the transition to MDR affect clinical evaluation?
The impact of transitioning from Directives to Regulations on clinical evaluations is multifaceted, but clinical evaluation itself is key for planning three major processes:
Scrutiny Process
Under the new scrutiny process, authorities may choose to re-review technical documentation prior to CE approval of high-risk devices. Article 44 requires notified bodies to submit new technical review reports, which may have an impact on submission timelines.
Reclassification
Under MDR, products may be required to change their classification, which is largely based on clinical evaluation data. Currently, products are classified according to risk. In this system, medical devices range from Class I (low risk) to Class AIMD (implanted cardiac pacemakers). With the transition to MDR, in vitro diagnostic devices from a General classification (requiring no notified body approval) may be reclassified to Annex II List A (requiring both notified body approval, as well as additional audits and reviews). Notified bodies will be required to participate in evaluating all but Class A devices. Upclassifications — such as in vitro fertilization diagnostics, spinal devices, and active implantable devices being redesignated as Class III or software deemed as Class IIa “devices” — are likely to be common.
Comparative Evaluations
MDR also specifies stricter requirements for comparative evaluations. More effort will be needed to demonstrate product safety and performance. This means manufacturers and their representatives will need to produce a greater volume of data, along with a more rigorous interpretation of that data. An additional complication is that approval will need to be obtained from comparison device manufacturers to present these evaluations.
When should clinical evaluation be conducted?
Clinical evaluation is an ongoing process throughout the life cycle of a medical device. This includes its design stage, which is the time point when an operational team should be brought onboard to start planning and strategizing.
However, clinical evaluation is most critical during CE marking in the form of CERs. From there, CERs should then be updated using clinical evaluation data at one or more of these time points:
- Annually for innovative or high-risk devices or every 2 to 5 years for well-established devices not expected to carry significant risks
- As new clinical data becomes available
- Changes are made to the product’s design or intended use
Frequency of CER updates should be justified by the manufacturer. Relevant factors, such as risk, scientific developments, and design changes, should be taken into account when planning this timeline.
How should clinical evaluation be performed?
Although it may be tempting, a wait-and-see approach isn’t the answer for this transitional period. Manufacturers and clinical research organizations (CROs) need to take proactive steps now to ensure all necessary data is available for future CERs.
Clinical evaluation is cyclical and comes in five major stages:
- Stage 0: Transition strategy, plan, gap analysis — the most important step from an operational perspective
- Stage 1: Identification of pertinent data — which data is important to collect during development?
- Stage 2: Collection and analysis of clinical data — where clinical trials begin
- Stage 3: CER preparation and post-marketing surveillance/post-market clinical follow-up plans — clinical evaluation is synthesized into one document and continues with post-market data
- Stage 4: Periodic updates — the CER is updated when necessary
This cycle starts over when the manufacturer wants to make major changes to a product or market a new product similar to an existing one.
What CER-related services can a CRO provide?
Clinical evaluation is a monumental task that more and more manufacturers are turning to CROs to handle. In addition to operationalizing the trials that go into clinical evaluation and managing data produced, CROs also often compile the information generated into writing the formal CER document. Likewise, a CRO can provide quality checks of CER documents either written internally or by a different organization. Another important job CROs may take on is providing gap analysis early in development, which can serve as an important guide during project planning.
Our experts are staying informed and developing the best methods of operationalizing MDR requirements in the coming months. In the meantime, if you’d like to learn more, you can read our previous blogpost covering the basics. Don’t hesitate to contact us with questions.