Italy – Regulatory Requirements and Considerations when Conducting Clinical Investigations with Medical Devices
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- Latest Updates
- Regulatory Requirements
- Regulatory Assumptions
- Submissions Documents
- Regulatory Classification
- Start-up Roadmap – Clinical Investigation of a Class I, or Non-Invasive Class IIa or IIb Medical Device that is Not CE Marked
- Start-up Roadmap – Clinical Investigation of an Invasive Class IIa or IIb Medical Device or a Class III Medical Device that is Not CE Marked Purpose
- Start-up Roadmap – Clinical Investigation of CE Marked Medical Device Used Within its Instructions and Intended Purpose
- Start-up Roadmap – Clinical Investigation of a Medical Device Used Within its Intended Purpose but with Additional Burdensome or Invasive Procedures (Article 74(1) PCMF)
- Study Conduct Considerations
- Definitions
- Useful Links
- History of Changes to this Page
Latest Regulatory Updates (⇑)
ITALY | NEW Guidelines for the Operating Regulations of the CETs
RWR CONTEXT The new Italian territorial ethics committees (CETs) are responsible for the review and approval of drug observational studies. These newly published operating guidelines will form the framework for the CET regional [...]
ITALY | Delay in Establishing Territorial Ethics Committees (CETs) in the Provinces of Trento and Bolzano
RWR CONTEXT Researchers are made aware that the Regions/Autonomous Provinces of Trento and Bolzano have missed the 7 June 2023 deadline to transition from the existing ethics committees to the new territorial ethics [...]
ITALY | Mandatory Substantial Amendment to Notify Transition to New Territorial Ethics Committees (CET)
RWR CONTEXT As of 7 June 2023, the mandate of the 40 new territorial ethics committees (CETs) comes into effect and the legal power of the previous ethics committees lapses. This means that [...]
ITALY | Ethical and Regulatory Issues in the Processing of Personal Health Data in Observational Research
RWR CONTEXT The National Coordination Center of Territorial Ethics Committees (CCNCE) has highlighted ethical and regulatory issues related to the processing of personal data in observational research, especially retrospective observational studies which focus [...]
ITALY | Significant Reform of the Ethics Committee Network
RWR CONTEXT As of 7 June 2023, the number of ethics committees competent to review drug observational studies is reduced from 90 to 40. This significant reform of the Italian ethics committee network [...]
Italy – New Regional Ethics Committee of the Abruzzo Region
RWR CONTEXT The research ethics committees of the south provinces of Chieti and Pescara and north provinces of L’aquila and Teramo have been replaced by the single Regional Ethics Committee of the Abruzzo [...]
Regulatory Requirements (⇑)
| wdt_ID | Country | Study Type | Approvals | Other Start-Up Requirements | Approval Timeframe |
|---|---|---|---|---|---|
| 1 | Italy | Clinical Investigation of Class I or Class IIa or IIb Non-Invasive Medical Device that is Not CE Marked | 1. Territorial Ethics Committee (CET) approval (fee = approx. €2500 - 4000 Euro) |
1. Notify the Directorate General for Medical Devices and Pharmaceutical Service (DGDMF) (fee = approx. €2245 Euro) | 12 to 20 weeks |
| 2 | Italy | Clinical Investigation of Invasive Class IIa or IIb or Class III Medical Device that is Not CE Marked | 1. Territorial Ethics Committee (CET) approval (fee = approx. €2500 - 4000 Euro) 2. The Directorate General for Medical Devices and Pharmaceutical Service (DGDMF) (fee = approx. €2245 Euro) |
Not Applicable | 12 to 20 weeks |
| 3 | Italy | Clinical Investigation of a Medical Device Used Within its Intended Purpose but with Additional Burdensome or Invasive Procedures (Article 74(1) PCMF) | 1. Territorial Ethics Committee (CET) approval (fee = approx. €2500 - 4000 Euro) |
1. Notify the Directorate General for Medical Devices and Pharmaceutical Service (DGDMF) at least 30 days before study start (fee = No fee) | 12 to 20 weeks |
| 4 | Italy | Clinical Investigation of CE Marked Medical Device Used Within its Instructions and Intended Purpose | 1. Territorial Ethics Committee (CET) approval (fee = approx. €2500 - 4000 Euro) |
1. Notify the Directorate General for Medical Devices and Pharmaceutical Service (DGDMF) (fee = No fee) | 12 to 20 weeks |
| Country | Study Type | Approvals | Other Start-Up Requirements | Approval Timeframe |
Regulatory Assumptions (⇑)
- In Italy, clinical investigations of medical devices are regulated according to the following 4 categories:
- Clinical investigations of Class I medical devices and non-invasive Class IIa and IIb medical devices.
- Clinical investigations of invasive Class IIa and IIb medical devices, and Class III medical devices.
- Clinical investigations of CE marked medical devices used within the intended purpose with additional burdens or invasive procedures.
- Clinical investigations of CE marked medical devices used within the intended purpose.
- All 4 categories require prior approval of a national ethics committee (CEN) or a territorial ethics committee (CET). Only one (1) ethics committee approval is required and is valid throughout Italy.
- The ethics committee approval should be obtained before submitting the application to the Ministry of Health (The Directorate General for Medical Devices and Pharmaceutical Service – DGDMF).
- Theoretically…the ethics committee and Ministry of Health submission can be made in parallel. HOWEVER..the Ministry of Health approval is dependent on the favourable opinion of the ethics committee. An inability to submit the ethics committee approval within the Ministry of Health validation and approval timeframe may (will) result in the application being voided.
- The annotated notes of the regulatory classification decision tree and start-up road maps can be downloaded HERE.
Submission Documents (⇑)
| wdt_ID | Submission Requirements | Details | References |
|---|---|---|---|
| 6 | Clinical Investigation of Class I or Class IIa or IIb Non-Invasive Medical Device that is Not CE Marked | 1. Letter of request, in Italian or bilingual Italian/English 2. Clinical investigation application form, in Italian or English, including an Appendix containing the list of documents supporting the application 3. Dossier for the investigator, including attachments such as, for example, manufacturer's instructions, label examples, instructions for use, list of general safety and performance requirements and applicable standards, summary of analyzes of risks, benefits and of risk management 4. Clinical investigation plan with synopsis of the clinical investigation in language and clinical evaluation plan, also in the form of details and/or references 5. Declaration signed by the person responsible for the manufacture of the device under investigation, specifying that the device in question complies with the general safety and performance requirements 6. Copy of the opinion / single opinion issued by the Ethics Committee / coordinating Ethics Committee depending on whether there are one or more testing centers in Italy 7. Proof of insurance coverage or compensation of the subjects in case of damage 8. Documents to be used to obtain informed consent, including the patient information sheet and the document on informed consent in Italian 9. Description of the provisions aimed at ensuring compliance with the applicable rules on the protection and confidentiality of personal data 10. Certification of payment of the fee of €2,245.20 11. Declaration in lieu of affidavit of the natural person acting as legal representative of the Sponsor 12. Declaration in lieu of the affidavit of the natural person acting as legal representative of the manufacturing manager 13. Copy of any power of attorney to the person who submits the application and is the recipient of communications from the Competent Authority 14. Documentation relating to the suitability of the healthcare facility(s) and the investigator(s). 15. List of testing centers and related ethics committees, including all their PEC addresses 16. Other documents, where applicable (e.g. Opinion of the group of experts, CE Certificates of Notified Bodies, Decisions of other Competent Authorities, PMCF Plan, Documentation of recruitment procedures and advertising material, any opinions of other Ethics Committees) |
Ref: Authorization for clinical investigation relating to class I or class IIa or IIb non-invasive medical devices not bearing the CE marking for the intended intended use Link: https://www.salute.gov.it/portale/moduliServizi/dettaglioSchedaModuliServizi.jsp?lingua=italiano&label=servizionline&idMat=DM&idAmb=SC&idSrv=PRE1&flag=P |
| 7 | Clinical Investigation of Invasive Class IIa or IIb or Class III Medical Device that is Not CE Marked | 1. Letter of request, in Italian or bilingual Italian/English 2. Clinical investigation application form, in Italian or English, including an Appendix containing the list of documents supporting the application 3. Dossier for the investigator, including attachments such as, for example, manufacturer's instructions, label examples, instructions for use, list of general safety and performance requirements and applicable standards, summary of analyzes of risks, benefits and of risk management 4. Clinical investigation plan with synopsis of the clinical investigation in language and clinical evaluation plan, also in the form of details and/or references 5. Declaration signed by the person responsible for the manufacture of the device under investigation, specifying that the device in question complies with the general safety and performance requirements 6. Copy of the opinion / single opinion issued by the Ethics Committee / coordinating Ethics Committee depending on whether there are one or more testing centers in Italy 7. Proof of insurance coverage or compensation of the subjects in case of damage 8. Documents to be used to obtain informed consent, including the patient information sheet and the document on informed consent in Italian 9. Description of the provisions aimed at ensuring compliance with the applicable rules on the protection and confidentiality of personal data 10. Certification of payment of the fee of €2,245.20 11. Declaration in lieu of affidavit of the natural person acting as legal representative of the Sponsor 12. Declaration in lieu of the affidavit of the natural person acting as legal representative of the manufacturing manager 13. Copy of any power of attorney to the person who submits the application and is the recipient of communications from the Competent Authority 14. Documentation relating to the suitability of the healthcare facility(s) and the investigator(s). 15. List of testing centers and related ethics committees, including all their PEC addresses 16. Other documents, where applicable (e.g. Opinion of the group of experts, CE Certificates of Notified Bodies, Decisions of other Competent Authorities, PMCF Plan, Documentation of recruitment procedures and advertising material, any opinions of other Ethics Committees) |
Ref: Authorization for clinical investigation relating to invasive class IIa or IIb or class III medical devices not bearing the CE marking for the intended intended use Link: https://www.salute.gov.it/portale/moduliServizi/dettaglioSchedaModuliServizi.jsp?lingua=italiano&label=servizionline&idMat=DM&idAmb=SC&idSrv=PRE2&flag=P |
| 8 | Clinical Investigation of a Medical Device Used Within its Intended Purpose but with Additional Burdensome or Invasive Procedures (Article 74(1) PCMF) | 1. Clinical investigation application form, in Italian or English, including an Appendix containing the list of documents supporting the application 2. Dossier for the investigator, including attachments such as, for example, manufacturer's instructions, label examples, instructions for use, list of general safety and performance requirements and applicable standards, summary of analyzes of risks, benefits and of risk management 3. Clinical investigation plan with synopsis of the clinical investigation in language and clinical evaluation plan, also in the form of details and/or references 4. Copy of the opinion / single opinion issued by the Ethics Committee / coordinating Ethics Committee depending on whether there are one or more testing centers in Italy 5. Proof of insurance coverage or compensation of the subjects in case of damage 6. Documents to be used to obtain informed consent, including the patient information sheet and the document on informed consent in Italian 7. Description of the provisions aimed at ensuring compliance with the applicable rules on the protection and confidentiality of personal data 8. Declaration in lieu of affidavit of the natural person acting as legal representative of the Sponsor 9. Copy of any power of attorney to the person who submits the application and is the recipient of communications from the Competent Authority 10. List of testing centers and related ethics committees, including all their PEC addresses 11. Other documents, where applicable (e.g. CE Certificates of Notified Bodies, PMCF Plan, Documentation of recruitment procedures and advertising material, any opinions of other Ethics Committees). |
Ref: Post Market Clinical Follow up (PMCF) clinical investigation notification with additional invasive or burdensome procedures Link: https://www.salute.gov.it/portale/moduliServizi/dettaglioSchedaModuliServizi.jsp?lingua=italiano&label=servizionline&idMat=DM&idAmb=SC&idSrv=POST1&flag=P |
| 9 | Clinical Investigation of CE Marked Medical Device Used Within its Instructions and Intended Purpose | 1. Sending the communication to the Ministry of Health includes - Completing an online form divided into 5 distinct sections - Data Communications Manager - Promoter Data - Clinical Center Data - Device Data - Survey Data 2. The transmission of the document produced at the end of completing the form according to the methods reported in How to submit the request. 3. Each transmission must contain only one completed online form: in the case of multiple forms, it is necessary to send as many submissions as there are. |
Ref: Communication of the start of clinical investigations Post Market Clinical Follow up (PMCF) Link: https://www.salute.gov.it/portale/moduliServizi/dettaglioSchedaModuliServizi.jsp?lingua=italiano&label=servizionline&idMat=DM&idAmb=SC&idSrv=POST2&flag=P |
| Submission Requirements | Details | References |
Regulatory Classification Decision Tree (⇑)
Start-Up Roadmap – Clinical Investigations of Class I, or Non-Invasive Class IIa or IIb Medical Devices that are Not CE Marked (⇑)
Start-Up Roadmap – Clinical Investigations of Invasive Class IIa and IIb, or Class III Medical Devices that are Not CE Marked (⇑)
Start-Up Roadmap – Clinical Investigation of CE Marked Medical Device Used Within its Instructions and Intended Purpose (⇑)
Start-Up Roadmap – Clinical Investigation of a Medical Device Used Within its Intended Purpose but with Additional Burdensome or Invasive Procedures (Article 74(1) PCMF) (⇑)
Study Conduct Considerations (⇑)
| wdt_ID | Study Conduct Requirements and Considerations | Details | References |
|---|---|---|---|
| 6 | Defintions | 1. For clinical investigation applications for medical devices not bearing the CE marking - For the purposes of this decree, the following apply [ref 1]: a) the definitions referred to in the art. 2 of Regulation (EU) 2017/745 relating to medical devices 2. For clinical investigations for devices bearing the CE marking used within their intended use - For the purposes of this decree, the following apply [ref 2]: a) the definitions referred to in the art. 2 of the Regulation (EU) 2017/745, relating to medical devices |
Ref1: Article 1(3) of Ministry of Health Decree of 12 April 2023 - Administrative procedures of national relevance for the submission of the clinical investigation application for medical devices not bearing the CE marking referred to in the art. 16, paragraph 2 of legislative decree no. 137 of 2022 Link: https://www.trovanorme.salute.gov.it/norme/dettaglioAtto?id=94514 Ref2: Article 1(3) of Ministry of Health Decree of 12 April 2023 - Administrative methods of national relevance for the presentation of communications relating to clinical investigations for devices bearing the CE marking used within their intended use referred to in the art. 16, paragraph 3 of decree no. 137 of 2022 Link: https://www.trovanorme.salute.gov.it/norme/dettaglioAtto?id=94513&articolo=1 |
| 7 | Approval Requirements for Clinical Investigations - General | 1. No clinical investigation can be started without sending suitable communication to the Ministry of Health and without them the conditions required for starting the investigation have been met [ref 1]. 2. The following are established by decree of the Minister of Health administrative procedures of national relevance for the presentation of the clinical investigation application for devices not bearing the CE marking and for those bearing the CE marking referred to in article 74, paragraph 2, of the regulation, providing that in documentation attached to it includes the favorable opinion expressed by the competent ethics committee. They are in the same decree indicate the procedures relating to the validation of the application and its relative evaluation, the issuing of the authorization and its relevant notification [ref 1]. 3. For devices belonging to class III and invasive devices belonging to classes IIa or IIb, applicants will only be able to initiate relevant clinical investigations after having obtained the relevant ministerial authorization from be issued within forty-five (45) days from the date of validation of the application for authorization, without prejudice to the possibility of extension this period of a further twenty (20) days for the purposes of any expert consultation [ref 1]. 4. For clinical investigations of class I devices or non-invasive class IIa and IIb devices, applicants can begin the clinical investigation thirty days after date of validation of the application, unless the Ministry of Health do not notify within this period that the application has been rejected for reasons of protection of public health, safety or security health of the subjects and users, as long as the ethics committee competent authority has given a favorable opinion in relation to the investigation clinic [ref 1]. |
Ref1: Article 16 of Legislative decree 05 August 2022, n. 137 - Provisions for the adaptation of national legislation to the provisions of Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 relating to medical devices, amending Directive 2001/83/EC, Regulation (EC) n. 178/2002 and Regulation (EC) no. 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC, as well as for the adaptation to the provisions of Regulation (EU) 2020/561 of the European Parliament and of the Council of 23 April 2020, which amends Regulation (EU) 2017/745 relating to medical devices, regarding the dates of application of some of its provisions pursuant to article 15 of law 22 April 2021, n. 53 Link: https://www.trovanorme.salute.gov.it/norme/dettaglioAtto?id=88953&articolo=16 |
| 8 | Approval Requirements for Clinical Investigations - Clinical Investigation of Class I or Class IIa or IIb Non-Invasive Medical Device that is Not CE Marked | 1. The procedure concerns the validation and evaluation of a clinical investigation application aimed at demonstrating the conformity of non-invasive class I or class IIa or IIb medical devices without CE marking (art. 62, par. 1, of EU Regulation 2017/ 745, hereinafter “Regulation”, identified at European level as the Medical Device Regulation, hereinafter “MDR”) [ref 1]. 2. The same procedure must be followed when a clinical investigation must be conducted to evaluate a device that already bears the CE marking but is used outside the scope of its intended use (art. 74, par. 2 MDR) [ref 1]. 3. Even devices bearing the CE marking that undergo significant changes in their structural characteristics are comparable, in the case of clinical investigation, to devices without the CE marking [ref 1]. 4. Before starting a clinical investigation to demonstrate compliance, an application must be submitted to the Ministry of Health (pursuant to art. 70, par.1 MDR) accompanied by all the documentation required by the Regulation (Annex XV, chapter II MDR) [ref 1]. 5. The Ministry verifies whether the application is complete, whether it falls within the scope of application of the Regulation and whether it falls within the provisions of the art. 62, par. 1, i.e. it can be considered an investigation for conformity assessment purposes (to establish and verify performance, clinical benefits, clinical safety of a medical device) [ref 1]. 6. In the event that the validation of the application is notified, the investigations can be started, and the Ministry of Health will continue the scientific evaluation activities, for the purposes of any corrective measures pursuant to art. 76 MDR [ref 1]. 7. Normally, an application for a clinical investigation is presented by the Sponsor of the clinical investigation (individual, company, institution or organization that takes on the responsibilities of initiating and managing the investigation, taking care of its financing) [ref 1]. 8. Within 15 days of receiving the application - The Ministry of Health informs the sponsor if the application is complete, if it falls within the scope of application of the Regulation and if it falls within the provisions of the art. 62, par. 1, i.e. it can be considered an investigation for conformity assessment purposes (to establish and verify performance, clinical benefits, clinical safety of a medical device). If the application dossier the investigation is incomplete or does not fall within those carried out for the purpose of assessing the conformity of the medical device, the sponsor has a period of 20 days from receipt of the communication from the Ministry to submit observations or complete the application [ref 1]. 9. Within 10 days of acquiring the additional information - The Ministry of Health informs the sponsor that the application has been validated or rejects the application if it believes that the application is not complete or that the clinical investigation does not fall within the scope of application of the Regulation or in any case of the art. 62, par. 1 [ref 1]. 10. Validation of the application can only be carried out if the positive opinion of an Ethics Committee has been formulated which can express a valid opinion at a national level (identifiable in the Ethics Committee responsible for the structure to which the coordinating investigator for Italy belongs, in the case of multicentre investigations involving multiple centers in Italy, or in the Ethics Committee responsible for the structure to which the principal investigator belongs, in the case of single-centre investigations in Italy) [ref 1]. 11. For clinical investigation questions relating to devices class I and non-invasive devices of classes IIa and IIb, of which to the art. 70, paragraph 7, letter a) of Regulation (EU) 2017/745, the opinion of the ethics committee valid at national level must be acquired by the Ministry of Health within thirty days from the date of validation of the application [ref 2]. 11. Clinical Investigation can Start 30 Days after the Validation Date - For clinical investigations of class I devices or non-invasive class IIa and IIb devices, applicants can begin the clinical investigation thirty (30) days after date of validation of the application, unless the Ministry of Health do not notify within this period that the application has been rejected for reasons of protection of public health, safety or security health of the subjects and users, as long as the ethics committee competent authority has given a favorable opinion in relation to the investigation clinic [ref 3]. |
Ref1: DGDMF - Authorization for clinical investigation relating to class I or class IIa or IIb non-invasive medical devices not bearing the CE marking for the intended use Link: https://www.salute.gov.it/portale/moduliServizi/dettaglioSchedaModuliServizi.jsp?lingua=italiano&label=servizionline&idMat=DM&idAmb=SC&idSrv=PRE1&flag=P Ref2: Article 4(5) of Ministry of Health Decree of 12 April 2023 - Administrative procedures of national relevance for the submission of the clinical investigation application for medical devices not bearing the CE marking referred to in the art. 16, paragraph 2 of legislative decree no. 137 of 2022 Link: https://www.trovanorme.salute.gov.it/norme/dettaglioAtto?id=94514&articolo=4 Ref3: Article 16(2) of Legislative decree 05 August 2022, n. 137 - Provisions for the adaptation of national legislation to the provisions of Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 relating to medical devices, amending Directive 2001/83/EC, Regulation (EC) n. 178/2002 and Regulation (EC) no. 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC, as well as for the adaptation to the provisions of Regulation (EU) 2020/561 of the European Parliament and of the Council of 23 April 2020, which amends Regulation (EU) 2017/745 relating to medical devices, regarding the dates of application of some of its provisions pursuant to article 15 of law 22 April 2021, n. 53 Link: https://www.trovanorme.salute.gov.it/norme/dettaglioAtto?id=88953&articolo=16 |
| 9 | Approval Requirements for Clinical Investigations - Clinical Investigation of Invasive Class IIa or IIb or Class III Medical Device that is Not CE Marked | 1. The procedure concerns the validation and evaluation of a clinical investigation application aimed at demonstrating the conformity of invasive class IIa or IIb or class III medical devices without CE marking (art. 62, par. 1, of EU Regulation 2017/745 , hereinafter "Regulation", identified at European level as the Medical Device Regulation, hereinafter "MDR") [ref 1]. 2. The same procedure must be followed when a clinical investigation must be conducted to evaluate a device that already bears the CE marking but is used outside the scope of its intended use (art. 74, par. 2 MDR) [ref 1]. 3. Even devices bearing the CE marking that undergo significant changes in their structural characteristics are comparable, in the case of clinical investigation, to devices without the CE marking [ref 1]. 4. Before starting a clinical investigation to demonstrate compliance, an application must be submitted to the Ministry of Health (pursuant to art. 70, par.1 MDR) accompanied by all the documentation required by the Regulation (Annex XV, chapter II MDR) [ref 1]. 5. The Ministry of Health verifies whether the application is complete, whether it falls within the scope of application of the Regulation and whether it falls within the provisions of the art. 62, par. 1, i.e. it can be considered an investigation for conformity assessment purposes (to establish and verify performance, clinical benefits, clinical safety of a medical device) [ref 1]. 6. If the validation of the application is notified, the Ministry of Health starts the scientific evaluation activities (art. 71 MDR) and at the end of the evaluation phase issues or refuses the authorization to conduct the investigation. 7. Any refusal of authorisation, after it has been assessed whether the potential residual risks are justifiable, taking into account the expected clinical benefits, is expressed with reasons referring to the art. 71 of the Regulation [ref 1]. 8.Normally, an application for a clinical investigation is presented by the Sponsor of the clinical investigation (individual, company, institution or organization that takes on the responsibilities of initiating and managing the investigation, taking care of its financing) [ref 1]. 9. The application of a Sponsor not established in the European Union must be submitted through its legal representative in the European Union (art. 62, par. 2, MDR), who is responsible for compliance with the Sponsor's obligations and is the recipient of all communications from the Competent Authority with the Sponsor [ref 1]. 10. A Sponsor may grant a power of attorney to a natural or legal person for the sole purpose of submitting the application and managing communications with the Ministry of Health (art. 38 Presidential Decree 445/2000) [ref 1]. 11. Within 15 days of receiving the application , the Ministry of Health informs the sponsor if the application is complete, if it falls within the scope of application of the Regulation and if it falls within the provisions of the art. 62, par. 1, i.e. it can be considered an investigation for conformity assessment purposes (to establish and verify performance, clinical benefits, clinical safety of a medical device). If the clinical investigation dossier is incomplete or does not fall within those carried out for the purpose of assessing the conformity of the medical device, the sponsor has a period of 20 days from receipt of the communication from the Ministry to submit observations or complete the application [ref 1]. 12. Within 10 days of acquiring the additional information , the Ministry of Health informs the sponsor that the application has been validated and the evaluation phase for authorization purposes has started or rejects the application if it believes that the clinical investigation is not complete or not falls within the scope of application of the Regulation or in any case of the art. 62, par. 1 [ref 1]. 13. The Regulation, with reference to the conditions of full operation of Eudamed, provides for a deadline of 45 days from the date of validation for the conclusion of the authorization procedure , which can be extended by a further 20 days in the case of expert consultation. The procedure can be suspended in order to request clarifications and additions from the Sponsor [ref 1] [ref 2]. 14. Validation of the application can be carried out only if the positive opinion of an Ethics Committee has been formulated which can express a valid opinion at national level (identifiable in the Ethics Committee responsible for the structure to which the coordinating investigator for Italy belongs, in the case of multicentre investigations involving multiple centers in Italy, or in the Ethics Committee responsible for the structure to which the principal investigator belongs, in the case of monocentric investigations in Italy) [ref 1]. |
Ref1: DGDMF - Authorization for clinical investigation relating to invasive class IIa or IIb or class III medical devices not bearing the CE marking for the intended use Link: https://www.salute.gov.it/portale/moduliServizi/dettaglioSchedaModuliServizi.jsp?lingua=italiano&label=servizionline&idMat=DM&idAmb=SC&idSrv=PRE2&flag=P Ref2: Article 4(6) Ministry of Health Decree of 12 April 2023 - Administrative procedures of national relevance for the submission of the clinical investigation application for medical devices not bearing the CE marking referred to in the art. 16, paragraph 2 of legislative decree no. 137 of 2022 Link: https://www.trovanorme.salute.gov.it/norme/dettaglioAtto?id=94514&articolo=4 |
| 10 | Approval Requirements for Clinical Investigations - Post Market Clinical Follow up (PMCF) Clinical Investigation Notification with Additional Invasive or Burdensome Procedures | 1. The procedure concerns the prior notification to the Ministry of Health, at least 30 days before the start, of PMCF investigations (clinical investigations for the further assessment of conformity), relating to medical devices bearing the CE marking and used according to the intended use in question. of the CE marking in which the subjects under study are subjected to additional invasive or burdensome procedures compared to those performed under the normal conditions of use of the device (art. 74.1 EU Regulation 2017/745, hereinafter "Regulation", identified at European level as Medical Device Regulation, hereinafter “MDR”). 2. The notification must be accompanied by all the relevant documentation required by the European Regulation EU 2017/45 (Annex XV, chapter II). 3. The notification is the responsibility of the sponsor fo eth clinical investigation. 4. Fee: The service is free |
Ref: DGDMF - Post Market Clinical Follow up (PMCF) clinical investigation notification with additional invasive or burdensome procedures Link: https://www.salute.gov.it/portale/moduliServizi/dettaglioSchedaModuliServizi.jsp?lingua=italiano&label=servizionline&idMat=DM&idAmb=SC&idSrv=POST1&flag=P |
| Study Conduct Requirements and Considerations | Details | References |
Definitions (⇑)
| Term | wdt_ID | Definition | Reference | Link |
|---|---|---|---|---|
| Clinical Investigation | 2 | ‘Clinical investigation’ means any systematic investigation involving one or more human subjects, undertaken to assess the safety or performance of a device. | Article 2(45) of Regulation (EU) 2017/745 | https://eur-lex.europa.eu/eli/reg/2017/745 |
| Clinical Investigation | 3 | Systematic investigation in one or more human subjects, undertaken to assess the clinical performance, effectiveness or safety of a medical device Note: For the purpose of this document, “clinical trial” or “clinical study” are synonymous with “clinical investigation” |
Section 3.8 of ISO 14155:2020 - Clinical Investigation of Medical Devices for Human Subjects — Good Clinical Practice | https://www.iso.org/standard/71690.html |
| Interventional Clinical Investigation | 4 | Interventional clinical investigation is a pre-or post-market clinical investigation where the assignment of a subject to a particular medical device is decided in advance by a CIP or diagnostic or monitoring procedures requested in the CIP are in addition to those available as normal clinical practice and burden the subject. | Section I.6.2 of Annex I of ISO 14155:2020 - Clinical Investigation of Medical Devices for Human Subjects — Good Clinical Practice | https://www.iso.org/standard/71690.html |
| Investigational Medical Device | 5 | Medical device being assessed for clinical performance, effectiveness, or safety in a clinical investigation. Note1: This includes medical devices already on the market that are being evaluated for new intended uses, new populations, new materials or design changes. Note 2: This includes medical devices already on the market that are being evaluated within their intended use in a post-market clinical investigation (interventional or non-interventional). Note 3: For the purpose of this document, the terms “investigational medical device” and “investigational device” are used interchangeably. |
Section 3.9 of ISO 14155:2020 - Clinical Investigation of Medical Devices for Human Subjects — Good Clinical Practice | https://www.iso.org/standard/71690.html |
| Medical Device | 6 | 1. ‘Medical device’ means any instrument, apparatus, appliance, software, implant, reagent, material or other article intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the following specific medical purposes: - diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease, - diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability, investigation, replacement or modification of the anatomy or of a physiological or pathological process or state, - providing information by means of in vitro examination of specimens derived from the human body, including organ, blood and tissue donations, and which does not achieve its principal intended action by pharmacological, immunological or metabolic means, in or on the human body, but which may be assisted in its function by such means. 2. The following products shall also be deemed to be medical devices: - devices for the control or support of conception - products specifically intended for the cleaning, disinfection or sterilisation of devices as referred to in Article 1(4) and of those referred to in the first paragraph of this point. |
Article 2(1) of Regulation EU/2017/745 | https://eur-lex.europa.eu/eli/reg/2017/745 |
| Term | Definition | Reference | Link |
Useful Links (⇑)
History of Changes to this Page (⇑)
| wdt_ID | Date | Impact | Category | Details |
|---|---|---|---|---|
| 4 | 18/11/2023 | Not Applicable | New Webpage | New page created to capture the regulatory requirements and considerations when conducting medical device clinical investigations in Italy. |
