Regulatory Pathway for Clinical investigation creates a set of clinical data that is crucial to understanding the effectiveness of a medical device.
Clinical Investigation is done for previously CE marked devices or for research medical devices. Clinical Investigation is governed by a clinical investigation plan with an objective, methodology, and record keeping.
Top 5 Steps involved in Clinical Investigation
Step 1
Appointment of a Representative- Appoint a legal representative.
Step 2
The application is made electronically via EUDAMED. A single identification number for the clinical investigation is generated. Within ten days of receiving the application, the Member State concerned shall notify the sponsor if the clinical investigation is within the scope of this Regulation and whether the application dossier is complete.
Until the EUDAMED is fully functional, contact the EU Commission authority of the individual member state for the complete set of procedures to be followed. A list of contact persons for Clinical Investigations can be found here.
Step 3
Assessment by the Member States
Conditions based on which the acceptance or refusal of Clinical investigation is mentioned in Article 71 of EU MDR.
Step 4
Proceed with Clinical investigation.
Step 5
Submission of results
Irrespective of the clinical investigation outcome, within one year of the end of the clinical investigation, the sponsor shall submit a clinical investigation report to all the Member States.
Documents required for application
The MDCG guidance document on Clinical Investigation also has the template for the list of documents required and the GSPR. Annex XV Chapter II of EU MDR also contains the complete list of documents required for submission.
The list of documents needed before the application of clinical investigation is as follows:
Application form
The application form can be accessed here.
- Name, address, and contact of the sponsor and, if applicable, name, address and contact details of its contact person or legal representative following Article 62(2) established in the Union.
- name and other details of the manufacturer
Investigator’s Brochure
Clinical Investigation Plan
Other information
- A statement by the natural or legal person responsible for the manufacture of the device under investigation that it conforms to the general safety and performance requirements.
- Where applicable, according to national law, copy of the opinion or opinions of the ethics committee or committees concerned.
- Proof of insurance cover
- Documents to obtain informed consent include the patient information sheet and the informed consent document.
- Full details of the available technical documentation, detailed risk analysis or any test reports, shall, be submitted to the competent authority reviewing an application upon request.
Modification of information in Clinical Investigation Plan
Modifications of the clinical investigation plan, investigators brochure, the subject information sheet, and other clinical investigation documentation may or may not be considered substantial modifications. The sponsor or representative must submit a notification of substantial modification following Article 75 of the EU MDR as soon as a clinical investigation is allowed to start.
It is not recommended to submit another substantial modification while the previous assessment is still ongoing. It is also essential to consider if national procedures may apply regarding modifications to clinical investigations.
Reporting Of Adverse Events
The sponsor or representative shall report, without delay, to all Member States in which the clinical investigation is being conducted. Sponsors or representatives should report the following:
- any adverse event identified as critical to the results of that clinical investigation.
- Any serious or adverse event.
- Any device deficiencies that might have led to an adverse event if appropriate action had not been taken.
- Any new findings of any event referred to in points 1-3.
Regulatory Pathway for Other Clinical Investigations (If the investigation is conducted not for conformity purpose)
Step: 01
Appoint a Legal Representative who is placed within the European Union. All communications relating to CI will be handled by the legal local representative.
Step: 02
Get an expert panel opinion from the Ethics Committee. This opinion from the Ethics Committee is valid within the entire Member State and the final opinion must not be a negative opinion.
Step:03
Fill up the Application form
Fill in the Clinical Investigation Application form
Also, attach necessary documents in the application as per the application guideline
Step: 04
Contact EU Commission
You will find the CI contact points details here
For research purpose investigations, each Member State shall define any additional requirements for such investigations, as appropriate for each Member State concerned.
Hence the Manufacturer must approach each Member state committee contact points to identify their local Investigation requirements.
Step: 05
Conducting Clinical Investigation
Clinical investigations shall be designed and conducted in such a way that the rights, safety, dignity and well-being of the subjects participating in a clinical investigation are protected and prevail over all other interests and the clinical data generated are scientifically valid, reliable and robust.
Clinical investigations shall be subject to scientific and ethical review. The ethical review shall be performed by an ethics committee in accordance with national law. Member States shall ensure that the procedures for review by ethics committees are compatible with the procedures set out in this Regulation for the assessment of the application for authorisation of a clinical investigation. At least one lay person shall participate in the ethical review.
Step: 06
Submit Clinical Investigation Report
Within 1 year of completion of the CI, the Sponsor (manufacturer) must submit the CI report to the concerned Member states.
Source of Information
EU MDR Article 82 states the Requirements for Research only Clinical Investigation (not for conformity purpose)
Article 62 (2) and (3), points (b), (c), (d), (f), (h), and (l) of Article 62(4) and Article 62(6).
FAQs
What are the obligations of a legal representative in Clinical investigations?
The obligation of a Legal representative includes:
- Submitting documents to the local authorities.
- Notification of clinical investigation.
- Reporting any adverse or serious events.
Who is responsible to report adverse events other than during Clinical investigations?
The sponsor is responsible to report adverse events only during Clinical Investigations. In case of general adverse events occurring in the field, the manufacturer is responsible.
What are the supporting documents required for applying Clinical Investigation request?
Mandatory documents:
- Cover letter
- Application form
- Investigator’s brochure
- Clinical Investigation plan
- Clinical Evaluation plan
- Synopsis
- Statement of Conformity
- Labels (examples)
- Description of the arrangements to comply with the applicable rules on the protection and confidentiality of personal data/ personal information
- List of General Safety and Performance Requirements
Listed below are as Applicable
Description of the arrangements to comply with the applicable rules on the protection and confidentiality of personal data/ personal information
Risk management documentation
Test reports
Proof of Clinical Investigation Insurance
Suitability of investigational sites and investigation site team
Manufacturer’s Instructions for Use
Suitability of the investigators
Recruitment procedures and advertising materials
Documents to obtain informed consent, informed consent procedure, all written information to participants, payments and compensation of participants
Notified Body Certificates
Decisions from other countries
PMCF plan
Expert panel opinion
Other documents