For post-market follow-up clinical investigations (PMCF CI) as per Art 74(1) MDR 2017/745, submissions to the Ethics Committee (EC) and the notification to the Competent Authority (CA) need to be done via DMIDS (Deutsches Institut für Medizinische Dokumentation und Information, German Medical Devices Information and Database System) as a sequential submission procedure.
This resembles the previous CI submissions as per §23b MPG (Medizinproduktegesetz, Medical Device Act) in connection with §7(3) MPKPV (Verordnung über klinische Prüfungen von Medizinprodukten, Ordinance on clinical investigations with medical devices) as an abbreviated submission: The EC performed a review of the full submission package, but for the CA it was a limited submission backage, and an approval of the CA was required. Although it seems similar, there are differences.
Per the MDR 2017/745 and Medizinprodukterecht-Durchführungsgesetz (Medical Device Law Implementation Act, MPDG), all Documents as listed in Annex XV Chapter II are to be included in the submission package, for the full review of the EC, and the notification to the CA.
A written positive opinion from an EC is required, but NO approval by the CA for the notification. The CI may commence after the positive opinion of the EC was obtained, and the earliest after 30 days of the notification to the CA.
The Clinical Investigation Identification number (CIV-ID) will be provided by the DMIDS as it was before.
This blog summarizes the current submission requirements for an Art. 74 (1) MDR PMCF Clinical Investigation in Germany, until EUDAMED is functional.
For which Clinical Investigations would this route apply?
The principle of ISO 14155:2020 Annex I post-market stage applies to clinical investigations as per MDR 2017/745 Article 74.1 PMCF clinical investigations and the Art. 82 other clinical investigations
– Article 74.1 PMCF clinical investigations fall under the post-market stage, and the confirmatory design and interventional aspects need to be taken into account for planning these studies.
CI per MDR Art.
Class of Device
Regulatory Status of Device
I through III
CE-marked, additional burdensome or invasive, for indications in Art. 62.1
Notification ≥ 30 days prior to commencement of study, positive opinion from an EC included.
Sequential Submission Flow
Since it is now a sequential submission process, the submission package for the initial submission needs to include all required documents, whether documents are only for CA review, or only EC review, or for both.
The EC’s favorable opinion will be included after EC review, when the notification to the CA will be performed.
Documents required to support a submission with respect to Annex XV, Chapter II MDR 2017/745 are listed below.
- Cover letter
- Billing address
- Clinical Investigation Plan (CIP)
- Investigator’s Brochure
- Synopsis of the CIP in German
- Description of procedure/investigational methods
- Preclinical evaluation
- Instructions for use in German
- Risk Assessment
- Assurance General Safety and Performance Requirements
- Plan for further treatment of subjects
- Power of attorney for representatives
- Results of biological safety assessment
- Proof of technical safety
- Functionality of Medical Device (MD)/information on MD
- Risk analysis and assessment including residual risks
- List of essential safety and performance requirements
- Safety reporting Declaration
- Information Investigational Site Feasibility
- Qualification of other personnel
- Qualification investigator
- Subject/patient information, declaration of consent
- Justification inclusion of particularly vulnerable persons
- Evidence of insurance
- Declaration of inclusion of dependent persons
- Declaration of data protection
- Financing of the Clinical Investigation/essential contractual contents
- Criteria or conditions and procedures for suspension or termination
- Summary risk assessment
- Evidence/data for sterile applied MP or sterilization validations
- CV of Investigator
- Proof of experience in the field of application of MD
- Proof of familiarity with basic principles of MD law
- Proof of familiarity with legal/scientific basics of the Clinical Investigation
- Demonstrated familiarity with CIP / IB
- Evidence of CE marking, also for the comparator device, if comparator controlled
- Clinical evaluation plan
- Information on the drug, tissue, or derivative
- Technical documentation
- Optional attachments
- The PDF form of the application, including the list of attachments, is automatically generated by the system
- 10 days for validation of the submission
- Date of confirming completeness is the validation date
- If the submission package is incomplete, the Sponsor has 10 days to complete the application
- Lead EC: 30 days for review after Validation Date, additional 15 days if an expert is to be involved
- Local EC: 20 days for review after Validation Date
- The EC may request additional information once during this time.
- Sponsor needs to provide the requested information within 45 days
- The EC will provide an opinion, either positive or negative for the CI
The reviewer clock-stops when additional documents are requested
- 30 days for review of the notification documents
- CI may start earliest 30 days after the notification if there is no negative opinion from an EC.
The reviewer clock-stops when additional documents are requested.
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