Clinical Evaluation Under MDR Article 61: What the File Needs

Every medical device placed on the Union market under the MDR carries a clinical evaluation in its technical documentation, class I included. The obligation is set by Article 61, the method by Part A of Annex XIV, and the output is a clinical evaluation report that a notified body, a competent authority or an authorised representative can ask to see. This article walks through what Article 61 requires, what the plan and the report must contain, when equivalence can carry the evidence, and where the evaluation of a lower-class device usually falls short.

What Article 61 requires

The first paragraph of Article 61 ties the clinical evaluation directly to the general safety and performance requirements:

"Confirmation of conformity with relevant general safety and performance requirements set out in Annex I under the normal conditions of the intended use of the device, and the evaluation of the undesirable side-effects and of the acceptability of the benefit-risk- ratio referred to in Sections 1 and 8 of Annex I, shall be based on clinical data providing sufficient clinical evidence, including where applicable relevant data as referred to in Annex III."

The same paragraph puts the judgement about how much evidence is enough on the manufacturer, and requires it to be justified:

"The manufacturer shall specify and justify the level of clinical evidence necessary to demonstrate conformity with the relevant general safety and performance requirements. That level of clinical evidence shall be appropriate in view of the characteristics of the device and its intended purpose."

Two definitions in Article 2 fix the vocabulary. Clinical evaluation is defined in Article 2(44) as "a systematic and planned process to continuously generate, collect, analyse and assess the clinical data pertaining to a device in order to verify the safety and performance, including clinical benefits, of the device when used as intended by the manufacturer;". Clinical evidence, in Article 2(51), means "clinical data and clinical evaluation results pertaining to a device of a sufficient amount and quality to allow a qualified assessment of whether the device is safe and achieves the intended clinical benefit(s), when used as intended by the manufacturer;". The word "continuously" in the first definition matters: a clinical evaluation is a process that runs for the life of the device, not a report written once before CE marking.

The three sources a clinical evaluation draws on

Article 61(3) sets the method. A clinical evaluation "shall follow a defined and methodologically sound procedure based on the following:" a critical evaluation of the relevant scientific literature, a critical evaluation of the results of all available clinical investigations, and "(c) a consideration of currently available alternative treatment options for that purpose, if any."

Literature about a different device counts only under two conditions, both written into point (a): equivalence has to be demonstrated in accordance with Section 3 of Annex XIV, and "the data adequately demonstrate compliance with the relevant general safety and performance requirements;". A reference list of papers on similar products, without an equivalence demonstration, does not meet either condition.

Point (c) is the one most often missing from class I files. The benefit-risk conclusion has to be read against what else is available to treat or manage the same condition. A compression bandage, an orthosis or a wound dressing competes with other devices and with non-device treatments, and the evaluation should say why the benefit-risk ratio of this device is acceptable in that context.

The clinical evaluation plan

Annex XIV Part A, Section 1(a) lists what the plan must contain at a minimum. It opens with "an identification of the general safety and performance requirements that require support from relevant clinical data;" and continues with the intended purpose, the target groups with indications and contra-indications, the intended clinical benefits with "relevant and specified clinical outcome parameters;", the methods for examining clinical safety, the parameters for judging the benefit-risk ratio against the state of the art, and a clinical development plan that runs through to post-market clinical follow-up.

The remaining points of Section 1 describe the work itself. The manufacturer must "(b) identify available clinical data relevant to the device and its intended purpose and any gaps in clinical evidence through a systematic scientific literature review;", appraise the data for suitability, generate new data through clinical investigations where needed, and "(e) analyse all relevant clinical data in order to reach conclusions about the safety and clinical performance of the device including its clinical benefits."

Section 2 sets the standard for the whole exercise: "The clinical evaluation shall be thorough and objective, and take into account both favourable and unfavourable data. Its depth and extent shall be proportionate and appropriate to the nature, classification, intended purpose and risks of the device in question, as well as to the manufacturer's claims in respect of the device." Proportionate does not mean optional. A class I device can have a short evaluation, but it cannot have none, and every claim made in the labelling or on the website has to be covered by it.

Equivalence: when another device's data can be used

Section 3 of Annex XIV allows a clinical evaluation to rely on data from an equivalent device, and sets three sets of characteristics that must be compared: technical, biological and clinical. The test for all three is the same:

"The characteristics listed in the first paragraph shall be similar to the extent that there would be no clinically significant difference in the safety and clinical performance of the device. Considerations of equivalence shall be based on proper scientific justification."

The last sentence of Section 3 is the practical barrier for most manufacturers: "It shall be clearly demonstrated that manufacturers have sufficient levels of access to the data relating to devices with which they are claiming equivalence in order to justify their claims of equivalence." For implantable and class III devices, Article 61(5) goes further and requires a contract giving full access to the other manufacturer's technical documentation on an ongoing basis. The Commission's guidance on this point is MDCG 2020-5 on clinical evaluation and equivalence.

When clinical investigations are required

Article 61(4) makes clinical investigations the default for implantable and class III devices, with narrow exceptions for modifications of the manufacturer's own marketed device, for certain legacy devices under paragraph 6(a), and for the well-established technologies listed in paragraph 6(b): "sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips or connectors". For lower-class devices, the Regulation does not prescribe a clinical investigation, but the level of evidence still has to be sufficient under paragraph 1.

When clinical data are not the right evidence

Some devices demonstrate conformity mainly through bench testing. Article 61(10) allows that route, but only with a documented justification:

"Without prejudice to paragraph 4, where the demonstration of conformity with general safety and performance requirements based on clinical data is not deemed appropriate, adequate justification for any such exception shall be given based on the results of the manufacturer's risk management and on consideration of the specifics of the interaction between the device and the human body, the clinical performance intended and the claims of the manufacturer."

The paragraph continues that the manufacturer "shall duly substantiate in the technical documentation referred to in Annex II why it considers a demonstration of conformity with general safety and performance requirements that is based on the results of non-clinical testing methods alone, including performance evaluation, bench testing and pre-clinical evaluation, to be adequate." Article 61(10) is not a waiver of clinical evaluation. It changes the evidence, not the obligation, and the justification is itself part of the clinical evaluation.

The clinical evaluation report and keeping it current

Article 61(12) fixes where the output lives: "The clinical evaluation, its results and the clinical evidence derived from it shall be documented in a clinical evaluation report as referred to in Section 4 of Annex XIV, which, except for custom-made devices, shall be part of the technical documentation referred to in Annex II relating to the device concerned." Section 4 of Annex XIV adds that "Both favourable and unfavourable data considered in the clinical evaluation shall be included in the technical documentation."

Article 61(11) keeps the report alive: "The clinical evaluation and its documentation shall be updated throughout the life cycle of the device concerned with clinical data obtained from the implementation of the manufacturer's PMCF plan in accordance with Part B of Annex XIV and the post-market surveillance plan referred to in Article 84." For class III and implantable devices, the PMCF evaluation report and, where indicated, the summary of safety and clinical performance are updated at least annually. The link between the two documents is explained in our note on the PMCF plan and evaluation report, and the reporting cycle in our note on the PSUR under Article 86.

Where class I clinical evaluations usually fall short

• No clinical evaluation plan. A report exists, but the requirements needing clinical support, the target population and the outcome parameters were never defined, so the conclusions cannot be tested against anything.

• Literature without equivalence. Papers on products of the same type are cited, but the technical, biological and clinical characteristics were never compared under Section 3 of Annex XIV.

• Claims outside the evidence. The instructions for use or the website claim a benefit, such as faster healing or pain relief, that the clinical evaluation does not address.

• No consideration of alternatives. The benefit-risk conclusion ignores the alternative treatment options required by Article 61(3)(c).

• A report that was never updated. Complaints, post-market surveillance data and new literature since CE marking are not reflected, which contradicts Article 61(11).

• An unjustified Article 61(10) route. Bench testing is presented as sufficient without the justification based on risk management and interaction with the body that the paragraph requires.

Class I manufacturers self-declare, so no notified body reviews the clinical evaluation before the device reaches the market. The first reader may be a competent authority during market surveillance. The quality system that has to keep the evaluation current is covered in our note on the QMS class I manufacturers cannot skip, and the structure of the file in our guide to technical documentation under Annexes II and III.

What the authorised representative checks

An authorised representative does not write or approve a clinical evaluation. Its role under Article 11(3)(a) is to verify that the EU declaration of conformity and the technical documentation have been drawn up, and the clinical evaluation report is part of that documentation under Article 61(12). Under Article 11(3)(d) the representative must also be able to provide the documentation to a competent authority on request, as set out in our note on competent authority requests. A missing or outdated clinical evaluation report is therefore one of the first things a representative asks about during due diligence.

Medex acts as EU authorised representative for manufacturers outside the Union under EUDAMED SRN TR-AR-000057550. We review the technical documentation, including the clinical evaluation report, before we accept a mandate. We are not a law firm and do not provide legal advice. To start, you can request a proposal.

The IVDR follows a different model for in vitro diagnostics, based on performance evaluation under Annex XIII, covered in our note on IVDR performance evaluation.