Clinical investigations of medical devices with CE mark, regulatory categorisation

Clinical investigations of medical devices with CE marking, regulatory categorisation

Manufacturers, as well as physicians working in science, are occasionally faced with the question of which regulatory requirements apply to them and their scientific project or clinical study if ALL of the following assumptions apply:

• planned clinical study
• involving study participants with diseases (patients)
• CE-labelled medical device within the intended purpose
• WITHOUT additional invasive or stressful procedures.

For all these cases, consultation with the ethics committee is required before the study can be started. The responsible ethics committee is that of the principal investigator for single-centre studies and that of the head of the clinical investigation for multi-centre studies. A higher federal authority does not have to be involved in each case.

ATTENTION: The above and the following examples apply ONLY to clinical studies that are conducted as described above within the intended purpose AND without additional invasive or stressful procedures with medical devices of risk class I and IIa (low and medium risk potential). For medical devices of a higher risk class (IIb and III, high and very high risk potential), the competent authorities must be involved!

Depending on the scenario, however, different further obligations may arise for the sponsor (manufacturer, researcher, etc.) depending on whether it is

1. a clinical investigation as part of the clinical evaluation for conformity assessment purposes, triggered by the manufacturer
2. a clinical investigation without being part of the clinical evaluation for conformity assessment purposes, initiated by the manufacturer
3. a clinical investigation to answer a scientific question, initiated by scientifically active physicians, clinics or university institutions.

In cases 1 and 2, a legal representative of the sponsor in the EU is required if the sponsor is based outside the EU.

It is therefore possible that clinical investigations may be necessary for reimbursement purposes to provide evidence of added benefit (e.g. comparison with competitors or current treatment practice) without being part of the PMCF plan. This applies, for example, to proof of medical(within the meaning of Section 139 SGB) or clinical(within the meaning of Art. 62 (1) b)) benefit, because this is required, for example, by the G-BA (Federal Joint Committee) or the BfArM (Federal Institute for Drugs and Medical Devices) with a view to reimbursement by statutory health insurance funds.

The following are practical examples to illustrate this:

Case examples for scenario 1: Manufacturer-initiated investigation as part of clinical evaluation

A manufacturer of a medical device initiates a clinical investigation as part of the clinical evaluation for conformity assessment purposes. As a result, Art. 62 - 81 MDR apply, but due to the inapplicability of Art. 74 (1) sentence 1 MDR, this type of study would not be explicitly covered by the provisions of the MDR and would also not be covered by the MPDG and the study could be conducted in Germany on the basis of professional consultation by the ethics committee and without the involvement of the authority.

Example 1:

A manufacturer conducts a clinical investigation as a prospective randomised controlled trial to confirm the accuracy and reliability of a new CE-marked digital blood pressure monitor. The study participants are not subjected to any additional invasive or stressful procedures. The ethics committee consults on the study without the involvement of the authority being required.

Example 2:

A manufacturer initiates a clinical investigation to investigate the effectiveness of its CE-marked nebuliser for the administration of medication for respiratory diseases as part of a single-blind monocentric study. The trial is part of the clinical evaluation for conformity assessment according to MDR. The study is reviewed by the ethics committee, but no additional regulatory approval is required.

Example 3:

A manufacturer tests a new electronic thermometer with a CE mark as part of a multi-centre study that promises faster and more accurate temperature measurement and continuous documentation. The clinical investigation is conducted as part of the clinical evaluation for conformity assessment. The ethics committee provides professional consultation and the authority is not involved.

Case examples for scenario 2: Manufacturer-initiated investigation outside the clinical evaluation

If a manufacturer of a medical device initiates a clinical investigation without this becoming part of the clinical evaluation for conformity assessment purposes, Art. 82 MDR is relevant. As a result, however, even in Germany, the conduct of the clinical investigation would only require professional consultation by the ethics committee without the involvement of the authority.

Example 1:

A manufacturer conducts a clinical investigation to assess the additional groove and safety of a CE-marked active motion splint for rehabilitation, which is not part of the clinical evaluation for conformity assessment purposes, but as part of a trial procedure.

Example 2:

A company develops a medical app to reduce weight and positively influence metabolic syndrome and conducts a clinical investigation to assess its effectiveness in comparison with existing products. This clinical investigation is not for the purpose of conformity assessment, but to optimise the product and improve its market position. The ethics committee consults on the study and no regulatory approval is required.

Example 3:

A manufacturer of medical software for smoking cessation seeks inclusion of its CE-marked medical device in the BfArM's DiGA Directory and conducts a decentralised digital clinical study; in addition to the minimum requirements, a long-term follow-up is also conducted. This clinical investigation is not intended for conformity assessment, but for reimbursement by the health insurance funds and to achieve a better negotiating position for pricing.

Case studies Scenario 3: Physician- or hospital-initiated trial (IIT)

Example 1:

A hospital is conducting a clinical investigation to study the effectiveness of a new wound dressing in healing chronic wounds. This study is initiated by the hospital's doctors and is regarded as a scientific question. The ethics committee consults on the study without the need for official authorisation.

Example 2:

A doctor initiates a clinical investigation to examine the diagnostic accuracy of a new type of laboratory test for the early detection of cancer. The study is classified as an internal scientific question and reviewed by the ethics committee without the need for regulatory approval.

Example 3:

A university hospital conducts a clinical investigation to evaluate the effects of a new physiotherapy programme on rehabilitation after knee surgery. This study is considered a scientific question and is being consulted by the ethics committee without the need for regulatory approval.

All of these scenarios were submitted for review and discussion to representatives of the AKEK (Working Group of Medical Ethics Committees), the BMBF (Federal Ministry of Education and Research), the German Medical Technology Association (BVMEd) and the Federal Institute for Drugs and Medical Devices (BfArM).

In summary, it can be stated that for clinical investigations of CE-labelled medical devices of risk classes I and IIa in Germany that are conducted within the intended purpose and without additional invasive or burdensome procedures, consultation with the responsible ethics committee is sufficient, regardless of the initiator (manufacturer or physicians), while involvement of the higher federal authority is not required, although different further obligations may arise for the sponsor depending on the scenario.

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