MDCG 2021-8 – Clinical investigation application/notification documents
Introduction
EUDAMED (electronic system referred to in Article 73 of the MDR) was deemed to be functionally in June 2022, instead of 26 May 2021, but this is still delayed. Per MDR 2017/745 Sponsors of clinical investigations are required to submit an application/notification to participating Member State(s) via EUDAMED.
The MDCG created guidance MDCG 2021-8 to support Sponsors and Competent Authorities in the submission processes for clinical investigation application/notification in the absence of the European EUDAMED.
MDCG 2021-8 Content:
The main part of this guidance document are the six Annexes included in and downloadable on the last page of this document.
These forms and templates provided by the MDCG may be helpful for the Competent Authorities and sponsors, though it is always requested to check with the relevant NCA if they require their own official application forms to be used.
Insofar as possible, the clinical investigation application/notification form includes the same data fields to the EUDAMED system in development and will be used until the EUDAMED module for clinical investigations is fully functional.
The Guidance also highlights the MDCG 2021-1 Rev.1, see more information below in “Other helpful MDCG Guidance”.
Annex 1: Clinical investigation – application/notification form under the Medical Device Regulation
The application/notification form incorporates fields the following information, which is based on the EUDAMED system under development, so this also gives a first overview what the EUDAMED module for clinical investigations will include.
1: Clinical investigation identification
1.1 Sponsor identification
1.2 Legal representative identification
1.3 Clinical investigation type
1.4 Submission type
1.5 Participating countries within the EU/EEA/UK (Northern Ireland), Turkey and Switzerland
1.6 Participating countries outside EU/EEA/UK
1.7 Clinical investigation plan (CIP)
1.8 Clinical investigation title
2: Clinical investigation description
2.1 Scientific opinion
2.2 Design of the clinical investigation
2.3 Design methodology
2.4 Development stage (Pilot stage, Pivotal stage, Post-market stage)
2.5 Objectives and endpoints
2.6 Synopsis of the clinical investigation
2.7 Planned number of subjects (In Europe: In Asia, In Africa, In North America, In South America, In Oceania, Total planned number of subjects)
2.8 Duration of clinical investigation
2.9 Population
2.9.1 Medical condition
2.9.2 Therapeutic area
2.9.3 Gender of subjects
2.9.4 Inclusion criteria
2.9.5 Exclusion criteria
2.9.6 Type of subjects that the clinical investigation plans to recruit (Healthy, Patients, Vulnerable population, Incapacited subjects, Minors, Pregnant women, Breastfeeding women, Patients in emergency situations, Other (please specify))
2.9.7 Age range of the participants that the clinical investigation plans to include (In utero, Newborns (from0 to 27 days), Infants and toddlers (from28 days to 23 months), Children (from 2 to 5 years), Adolescents (from 12 to 17 years), Adults (from 18 to 84 years), Elderly (from 85 years))
2.10 Scope of the investigational device
2.10.1 Combined investigation Medical Device/In Vitro Diagnostic? – if this is the case, Annex 2 Additional investigational device(s) shall be completed.
2.10.2 Is the application submitted in parallel with an application for a clinical trial on medicinal products? This refers to a parallel study, not to a study with a combination device, classified as medical device, see also: MDCG 2021- 24, MDCG 2022-5, and Helsinki Procedure 2021
2.11 Coordinating investigator
3: Investigational device(s)
3.1 Investigational medical device
3.1.1 Device purposes
3.1.2 Device type
3.1.3 Invasiness
3.1.4 Device Identifiers
3.2 Previous clinical investigation
3.3 Scientific opinion/view
3.4 Manufacturer of the investigational device
3.4.1 Manufacturer information
3.4.2 Authorised representative
4: Comparator ((Therapy, Placebo, No treatment, Medical device)): if there are more than one comparators Annex 3 Additional comparator device(s) shall be completed.
5: National information
5.1 Study site information
5.2 Ethics committee information
5.3 Status of the clinical investigation
5.4 Expected number of subjects recruited within the Member State
The form can be signed digitally (PDF signature).
Annex 2: Additional investigational device(s) (section 3)
This is a duplicate of Section 3, Pages 13 through 16 of the application form if more than one investigational device is used in the study.
Annex 3: Additional comparator device(s) (section 4)
This is a duplicate of Section 4, Pages 17 and 18 of the application form if more than one comparator (Therapy, Placebo, No treatment, Medical device) is used in the study.
Annex 4: Additional investigation site(s) (section 5)
This is a duplicate of section 5, page 19 of the application form for additional national sites, should be completed for each participating country: .5.1 Study site information
Annex 5: Clinical investigation supporting documents – Appendix of documents to attach
The use of the checklist is not mandatory, but is recommended to be used for traceability, in conjunction with the document clinical investigation application form.
The relevant NCA regarding expectations should always be checked, as there might be additional required documents in a single Member state.
Mandatory documents required to support a submission with respect to Regulation 745/2017 are:
- Cover letter
- Application form
- Investigator’s Brochure (including any annexes) (if applicable)
- Clinical investigation plan
- Clinical evaluation plan
- CIP synopsis
- Statement of conformity
- Example of labels
- 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
As applicable documents might be required, depending on the type and regulatory stage of the clinical investigation:
- 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 form other countries
- PMCF plan
- Expert panel opinion
- Other documents
Annex 6: Checklist of general safety and performance requirements, Standards, common specifications, and scientific advice
This is well known from the essential requirements checklist under MDD/AIMDD. With the MDR 2017/745, it is now the general safety and performance requirements (GSPR) checklist, so it has been updated to the GSPR as per Annex I, chapter I, II and III of the MDR. MDR 2017/745 Annex XV, chapter II, section 2.7 lists this document to be included in the submission package for information on investigational medical devices.
New to this checklist is the first part to include information on standards, common specifications, and scientific advice obtained from expert panels according to articles 9 and 106 MDR (Provision of scientific, technical and clinical opinions and advice). For more information on this, see:
- COMMISSION IMPLEMENTING DECISION (EU) 2019/1396 of 10 September 2019, laying down the rules for the application of Regulation (EU) 2017/745 of the European Parliament and of the Council as regards the designation of expert panels in the field of medical devices
- The European Commission website listing experts appointed by the Commission as advisors to expert panels: Expert panels (europa.eu)
Other helpful MDCG Guidance
- MDCG 2020-10-1 Guidance on safety reporting in clinical investigations and MDCG 2020-10-2 Clinical Investigation Summary Safety Report Form v1.0
- MDCG 2021-6 Regulation (EU) 2017/745 – Questions & Answers regarding clinical investigation
- MDCG 2021-20 Instructions for generating CIV-ID for MDR Clinical Investigations, see also our blog: Summary of the MDCG Guidance Document MDCG 2021-20
- MDCG 2021-28 Substantial modification of clinical investigation under Medical Device Regulation
- The MDCG 2021-1 Rev.1 Guidance on harmonised administrative practices and alternative technical solutions until EUDAMED is fully functional (respectively referrals to: Art. 70, Art. 73, Art. 74, Art. 75, Art. 76, Art. 77, Art. 78, Art. 80), see also our blog: Summary of the MDCG Guidance Document MDCG 2021-20
- MDCG 2019-9 Rev.1 Summary of safety and clinical performance A guide for manufacturers and notified bodies
Helpful guidance is provided for the Classification of Devices and Combination Products Medical Device and Medicinal Product:
- MDCG 2022-5 Guidance on the borderline between medical devices and medicinal products under Regulation (EU) 2017/745 on medical devices
- MDCG 2021-24 Guidance on classification of medical devices
- Exchange of information between medical device competent authorities on borderline and classification cases Helsinki Procedure 2021
In addition, helpful guidance is provided for “actors” registration under MDR:
- MDCG 2020-15: MDCG Position Paper on the use of the EUDAMED actor registration module and of the Single Registration Number (SRN) in the Member States
- MDCG 2021-13 rev.1: Questions and answers on obligations and related rules for the registration in EUDAMED of actors other than manufacturers, authorised representatives, and importers subject to the obligations of Article 31 MDR and Article 28 IVDR
Thank you for your time. If you found this interesting, please check-out for out next blog on the MDCG Document summaries: MDCG 2021-28 Substantial modification of clinical investigation under Medical Device Regulation
