EU MDR sets out the general requirements on clinical investigations with medical devices in Chapter VI and Annexes XIV and XV. Focusing on Spain, the Ministry of Health is currently finalizing the details of the new royal decree on medical devices that will replace the previous regulation. This new royal decree introduces modifications with the aim of making possible the application of the EU MDR and developing those aspects that the latter leaves to the development of national legislation (Spanish MDR).

In order to comply with the provisions of the EU MDR and the (coming) Spanish MDR, AEMPS has recently renewed the application procedure for the authorization of clinical investigations with medical devices in Spain. Accordingly, the AEMPS has published a set of practical instructions for sponsors of clinical investigations clarifying the various types of clinical investigations together with the applicable regulatory requirements and the procedure to apply for the authorization from the AEMPS, including the documents and information that must accompany the application. The instructions will be updated in the light of experience gained and guidelines published at EU level.

Clinical investigations and applicable regulatory requirements

Application for authorization of clinical investigations

The application for authorization of clinical investigations consists of different phases, including initiation, validation, evaluation, modification and final report. Leaving aside more formal issues, interactions with the AEMPS and deadlines, it is worth highlighting the following:

• The authorization is requested in writing by the sponsor, accompanied by the documents described in Chapter II of Annex XV to the MDR and proof of payment of the fee. Until the EU database on medical devices (EUDAMED) is available, the set of documents is submitted through the General Electronic Registry of the General State Administration addressed to the AEMPS.

• Given the short deadlines for evaluation and issuance of the decision authorizing or denying the application, it is highly advisable recommended that the Ethics Committee evaluates the clinical investigation in time. It is even recommended to submit the application for authorization with the favorable opinion of the Ethics Committee already issued or at an advanced stage of receiving it.

• Any substantial modification in the authorized conditions for a clinical investigation, understood as that could have a substantial impact on the safety, health or rights of the subjects, or on the soundness or reliability of the clinical data generated by the investigation, requires the prior favorable opinion of the Ethics Committee and the authorization of the AEMPS (e.g., extensions of clinical investigations already authorized to new sites). If the modification refers exclusively to specific documents that must be evaluated only by the Ethics Committee or only by the AEMPS, only the favorable opinion of the former or the authorization of the latter would be required.

• In terms of termination, temporary suspension or early termination, the sponsor has a series of reporting obligations to the AEMPS within certain deadlines. In addition, when the duration of the clinical investigation exceeds one year, the sponsor is required to submit an annual report on the progress of the clinical investigation to the AEMPS.

Other requirements at national level

Among other national requirements highlighted by the AEMPS (e.g., manufacturing, importation, ethical postulates, documentation filing or safety notifications), certain language and insurance coverage requirements will apply:

• Regarding language requirements, the new Spanish MDR will require that certain documents are submitted at least in Spanish. In order to facilitate and promote investigation in Spain, and provided that the Ethics Committee has no objection, the clinical investigation plan and the investigator’s manual could be accepted in English. However, the AEMPS may request their translation, as well as that of any other document in the dossier. The instructions for use and labeling, the summary of the clinical investigation plan, the patient information and informed consent form, and the request for authorization or notification must be submitted in Spanish.

• As concerns insurance coverage, in clinical investigations with medical devices non-CE-marked or CE-marked to evaluate an intended purpose other than that covered by their marking, there should be coverage mechanisms in the form of insurance, guarantee or a similar arrangement.

Next steps

We routinely advise clients on these, and other, complex challenges in the medical device industry. For more details on clinical investigations in Spain and the new instructions issued by the AEMPS.