Challenge of a
CLINICAL AFFAIRS under MDR
Medical devices must be safe and perform well. To prove this, a clinical evaluation is required. The European Medical Device Regulation (MDR) 2017/745, like the still valid EU Medical Device Directive (93/42/EEC, MDD), requires that all medical device manufacturers to conduct a clinical evaluation and post-market clinical follow-up (PMCF) for all their devices, regardless of risk class. The clinical evaluation is an essential part of the conformity assessment procedure for CE marking and must be performed before the approval and the placing on the market.
What is a Clinical Evaluation
A clinical evaluation is a systematic and planned process by which clinical data of the medical device are generated, compiled, analyzed and finally evaluated. The result of the clinical evaluation is the Clinical Evaluation Report (CER), with which the manufacturer demonstrates the conformity of the medical device with the general safety and performance requirements according to Annex I of the MDR. The Clinical Evaluation Report (CER) is an important part of the technical documentation of the medical device as well as an integral part of a manufacturer’s quality management system (MDR Article 10 (3), (9f)). It must be actively updated on a regular basis using data from post-market surveillance of the medical device and from the post-market clinical follow-up (PMCF). Clinical evaluation is thus an ongoing process during the entire life cycle of the medical device.
Purpose of the clinical evaluation
The purpose of the clinical evaluation is to demonstrate safety and performance, including the clinical benefits, when the medical device is used as intended. In addition, the clinical evaluation can be used to identify unrecognized risks or hazards and to reassess risks. Using up to date clinical data, manufacturers shall reassess the acceptability of risks.
The Clinical evaluation objectives include:
As part of the clinical evaluation, alternative products, procedures and technologies that can be used instead of the treatment under evaluation, are assessed and documented. The clinical evaluation must ensure that the product under evaluation is not inferior to the possible alternatives. The state of the art must be described and evaluated in the clinical evaluation. Clinical benefits, safety, and performance should be taken into consideration when evaluating the state of the art. Medical device manufacturers must consider the state of the art when developing and manufacturing their products. According to the ISO 14971 standard, “state of the art” is defined as: ” Developed stage of technical capability at a given time as regards products, processes and services, based on the relevant consolidated findings of science, technology, and experience. The state of the art embodies what is currently and generally accepted as good practice in technology and medicine. The state of the art does not necessarily imply the most technologically advanced solution. The state of the art described here is sometimes referred to as the “generally acknowledged state of the art”. “
Clinical evaluation data
The clinical evaluation is based on clinical data obtained during the use of the medical device. These can come from the following sources:
According to MDR, Article 2 (48), clinical data are data on safety and performance obtained in the context of the use of a device. For the literature search of the clinical evaluation, the MEDDEV 2.7/1 Revision 4 is the most important guideline, also under the MDR. The literature search should consider the “state of the art,” the medical device being evaluated, and any existing equivalent products. The clinical evaluation must be thorough and objective and should consider favorable as well as unfavorable data.
In addition to clinical data, manufacturers must also consider preclinical data for their clinical evaluation. This includes, for example, results from the following tests: Biocompatibility testing, Electrical and mechanical safety according to IEC 60601-1, Electromagnetic compatibility according to IEC 60601-1-2, Usability testing, Software testing, Animal testing, Simulations, Laboratory testing, Durability and stability testing.
A waiver of clinical data is possible according to MDR Article 61 “Clinical Evaluation” Section 10, for absolutely non-critical products (stand-alone software, oral spatulas, dental drills, etc.) and must be justified by the manufacturer based on risk management. This justification takes into account the specific interactions between the device and the human body, the intended clinical performance, and the manufacturer’s claims. In this case, the manufacturer must justify in the technical documentation, according to Annex II of the MDR, why they considerit appropriate to demonstrate compliance with the general safety and performance requirements based solely on the results of non-clinical test methods, including performance evaluation, technical testing and pre-clinical evaluation.
Clinical evaluation according to the
"equivalence route" principle
So far, clinical data from potential equivalence products could be considered in the clinical evaluation. The MDR, as well as the requirements of MEDDEV 2.7/1 Revision 4 and the MDCG (Medical Device Coordination Group) guideline “MDCG 2020-5 (Guidance on Clinical Evaluation – Equivalence)” restrict this possibility by strengthening the requirements.
In the future, the clinical evaluation may only be based on clinical data for an equivalent product if the similarity (equivalence) between the similar product and the product in question is robustly demonstrated in the clinical evaluation. There must be no clinically meaningful difference in the safety and clinical performance of the products. The assessment of similarity must take into account clinical, biological, and technical characteristics and requires adequate scientific justification….
The three characteristics of equivalence must all be cumulatively fulfilled and substantiated in accordance with the requirements of the MDR in order to be allowed to be included in the clinical evaluation process of the device under evaluation. Equivalence can only be demonstrated on the basis of a single medical device. Manufacturers may use data from multiple equivalence products if each is equivalent in all three characteristics (technical, biological, clinical) and the evidence of equivalence is based on valid scientific data (clinical data from literature, preclinical data from technical documentation, etc.).
If there is no equivalence, the manufacturer may not use the clinical data of the other product to demonstrate safety, performance, and clinical benefits.
The clinical data referenced by a manufacturer in the equivalence evaluation must provide sufficient clinical evidence (“Clinical Evidence”). According to Article 2 (51) of the MDR, “Clinical Evidence” means the clinical data and clinical evaluation results on a device that are sufficient in quantity and quality to make a qualified judgment as to whether the device is safe and achieves the intended clinical benefits when used as intended, as claimed by the manufacturer. The level of clinical evidence must be appropriate to the characteristics of the device and its intended use.
Manufacturers must also demonstrate that they have sufficient access to data on equivalent products to adequately support the claimed similarity. In the absence of data regarding some attributes, manufacturers may generate them through their own testing. Manufacturers who do not have sufficient clinical evidence from equivalence products must generate clinical data via clinical trials with their own product.
The innovations of the MDR will thus lead to an increase in time-consuming and cost-intensive pre-market clinical trials with the medical device under evaluation.
Clinical Evaluation Plan (CEP).
Clinical evaluation is a systematic and planned process for the continuous generation, collection, analysis and evaluation of clinical data on a medical device. According to Article 61 (paragraph 12) and Annex XIV Part A “Clinical Evaluation” of the MDR, manufacturers are required to prepare and update a clinical evaluation plan (CEP). This plan already defines the basic principles, such as the objectives and structure for the clinical evaluation. In the CEP, the manufacturer determines the basic safety and performance requirements to be supported with relevant clinical data. It specifies the intended purpose and intended target populations with clear indications and contraindications, and describes the intended clinical benefits to the patient with specific clinical outcome parameters.
In addition, a clinical development plan (CDP) for planning pertinent designed clinical trials, including a post-market clinical follow-up plan (PMCF plan), is a new mandatory part of the clinical evaluation plan. These changes place greater emphasis on clinical data. The Clinical Development Plan (CDP) outlines at the beginning of the development process how the manufacturer will obtain new or additional clinical data needed to address open “gap analysis” questions, through clinical trials or observational studies. Clinical trials are conducted on human subjects to evaluate the clinical performance or medical efficacy and safety of medical devices.
Clinical design ranges from exploratory studies (e.g., first-in-man studies, proof-of-concept or feasibility studies, and pilot studies) to collect initial clinical data, to confirmatory studies (e.g., pivotal clinical trials), the outcome of which is critical to subsequent marketing authorization, and post-market clinical follow-up in accordance with Part B of Annex XIV.
Post-marketing clinical follow-up studies (PMCF studies) are used, for example, to evaluate long-term safety and efficacy, to determine clinical performance, to identify rare adverse reactions, or to detect interactions with other products/drugs. When planning clinical trials, staging objectives and possible acceptance criteria should be described in accordance with the MDR. The stepwise approach to planning allows for a cautious approach, especially with new technologies, materials, or medical procedures, and thus minimizes residual or unknown risks to patients.
Class III. devices and implantable devices
For implantable devices and Class III devices, a clinical investigation is generally required in accordance with MDR clinical data collection requirements. The few exceptional cases include:
Modified products of an already approved product from the same manufacturer
The following conditions apply in accordance with MDR Article 61, Section 4:
Similar products of an already approved product of another manufacturer
In accordance with MDR Article 61, Section 5, the following terms apply in addition to the requirements of Section 4:
Thus, it is not possible to claim similarity with already approved products of another manufacturer that were placed on the market under the still valid European directives 93/42/EEC (Medical Device Directive, MDD) or 90/385/EEC (Active Implantable Medical Devices, AIMDD).
Devices that have been lawfully placed on the market or put into service in accordance with Directive 90/385/EEC or Directive 93/42/EEC
The following conditions apply in accordance with MDR Article 61, Section 6:
Certain products according to MDR Article 61, Section 6
(sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, dental or bone plates, wires, pins, clips, connectors) under the following conditions:
For products without medical purpose
(MDR Annex XVI, e.g.: Contact lenses, devices for liposuction, lipolysis or lipoplasty, devices for transcranial stimulation of the brain) can only be waived according to Article 61, Section 9, if there are sufficient reasons to rely on already existing clinical data on an analogous medical device.
MEC-ABC, your "guide" to
clinical data under MDR
We support you in generating, collecting and updating clinical data for the entire life cycle of your products. MEC-ABC acts as a guide, providing advice to help you understand and correctly apply all regulatory requirements.
Our experts will prepare for you the clinical evaluation plan (CEP) and clinical evaluation report (CER) for all classes of medical devices (Class I, IIa, IIb, III) according to the requirements of the MDR.