A Comprehensive Pre-Submission Readiness Guide

Navigating the European Union’s (EUs) Medical Device Regulation (Regulation [EU] 2017/745; MDR) demands meticulous preparation. Submitting incomplete technical documentation to a Notified Body (NB) for review triggers lengthy review cycles and costly delays. This guide serves as a final gap analysis to ensure a robust, coherent, and compliant submission, paving a smoother path to Conformité Européenne (CE) marking.

Step 1: Cross-Product & Organisational Requirements

Your technical documentation is an output of your quality management system (QMS). The NB will review your technical file and your QMS, in accordance with the requirements of Annex IX of the MDR. Other conformity assessment routes, such as those outlined in Annex X (based on type-examination) or Annex XI (based on product conformity verification), may also be selected, although they are less commonly used.

The foundational systems and roles required of all manufacturers, regardless of device classification, are as follows:

• MDR-compliant QMS: Per MDR Article 10(9), a QMS for developing, manufacturing, and post-market monitoring is mandatory. Although certification to ISO 13485:2016 is not mandatory, it is commonly used to demonstrate compliance and is considered the most effective way to fulfil the requirements of Article 10(9) of the MDR. For all devices, the QMS should incorporate MDR-specific processes such as post-market surveillance (PMS), vigilance, and unique device identification (UDI) management.

For Class IIa, IIb, and III devices, as well as certain Class I devices placed on the market in sterile condition, with a measuring function, or intended to be reused, the QMS is typically assessed by a Notified Body as part of the conformity assessment. For other Class I devices, while a QMS is still required under Article 10(9), it does not require Notified Body involvement.

• Risk management system: Mandated by MDR Annex I, risk management per ISO 14971 must be a continuous process implemented throughout the entire product lifecycle, ensuring risks are controlled and an acceptable benefit-risk ratio.
• Person Responsible for Regulatory Compliance (PRRC): MDR Article 15 obliges manufacturers to designate at least one qualified PRRC permanently and continuously at their disposal. This ensures technical documentation and declarations of conformity (DoC) are prepared and maintained in compliance with the Regulation.
• Understanding stakeholder obligations: Ensure that your organisation understands, and has communicated, the necessary information to distributors and importers, who have specific obligations under MDR Articles 13 and 14 regarding verification, storage, and complaint handling.

Step 2: Product-Specific & Technical Documentation Requirements

Your technical documentation is the core evidence dossier for your device, structured in accordance with MDR Annexes II (Technical Documentation) and III (Technical Documentation on PMS).

Technical documentation (Annex II)

Must provide comprehensive evidence that all General Safety and Performance Requirements (GSPRs) from Annex I are met.

• Device description & specifications: Detailed description of the device, including trade name, intended purpose, users, patient population, principles of operation, and key functional elements (components, materials, software). Identification via Basic UDI-DI (per MDR Article 27 and Annex VI, Part C) or other traceable identifiers. Justification of device qualification, risk class, and applied classification rules in accordance with MDR Annex VIII. Overview of previous and similar generations of the device
• Labelling & Instructions for Use (IFU): All labelling must comply with MDR Annex I, Chapter III. Claims made in the IFU or labelling must be consistent with, and supported by, the clinical evaluation, GSPRs, and RMF. Labels and Instructions for Use (IFU) in all applicable EU languages
• Design and Manufacturing Information: Description of design stages, manufacturing processes, validation data, and control of critical suppliers/subcontractors.
• GSPR checklist: Links each applicable safety and performance requirement of the device to the source of objective evidence (ie, verification & validation [V&V] reports, test data, or procedures); GSPRs not considered applicable should be justified. Reference to applied harmonised standards, common specifications (CS), or equivalent solutions.
• Risk management file (RMF): Must demonstrate a complete lifecycle approach to risk per ISO 14971, including analysis, evaluation, control, and a report concluding a favourable benefit-risk profile.
• V&V reports: Data supporting device safety and performance, including
  • Biocompatibility (ISO 10993 series)
  • Electrical Safety & electromagnetic compatibility (IEC 60601 series)
  • Software V&V (IEC 62304 for lifecycle processes)
  • Stability and shelf-life testing
  • Sterilisation validation
  • Performance and safety testing relevant to intended use

Clinical Evaluation (Annex XIV)

Includes a clinical evaluation report (CER) based on a compliant clinical evaluation plan (CEP), providing sufficient clinical evidence to demonstrate device safety, performance, and a favourable benefit-risk ratio. It must also:

• critically appraise data from manufacturer clinical investigations or an equivalent device (if claimed according to strict MDR criteria);
• be updated continuously throughout the device’s lifecycle with post-market data.

PMS & vigilance (Annex III)

The Post-Market Surveillance (PMS) Documentation ensures continuous evaluation of device performance and compliance throughout its lifecycle, through the following documents.

• A PMS plan: Proactively and systematically collects and analyses post-market data on device quality, performance, and safety.
• A post-market clinical follow-up (PMCF) plan: Actively gathers clinical data post-market, required unless exclusion is justified.
• Vigilance System: Robust procedures for reporting Serious Incidents and Field Safety Corrective Actions to competent authorities per MDR Article 87.
• PMS reporting: Preparation of a Periodic Safety Update Report (PSUR) (Article 86) or Post-Market Surveillance Report (PMSR) (Article 85), depending on device class

Step 3: Pre-Submission – Administrative and Conformity Assessment Planning

Final checks before NB engagement.

• Conformity assessment: Based on device classification, the correct conformity assessment procedure (detailed in MDR Annexes IX-XI) must be followed.
• EU DoC (Annex IV): A draft DoC must be prepared, listing all applicable regulations and standards, signed after the NB grants CE certification.
• Summary of Safety and Clinical Performance (SSCP): For implantable and Class III devices; must be written in clear, layperson language and must be consistent with the CER and IFU.
• CRITICAL STEP – Internal Consistency Review: A cross-functional review to ensure the device name, intended purpose, indications, and key performance claims are consistent across documentation.
• NB Engagement:
  • Designation Scope: Confirm your chosen NB is officially designated for your device type and classification.
  • HIGHLY RECOMMENDED – Pre-Submission Meeting: Discuss your strategy and the NB’s expectations through structured dialogues, de-risking the formal submission process.

Supporting Documents and Guidance

EU MDR 2017/745 Harmonized Standards:

• ISO 13485:2016 (QMS)
• ISO 14971:2019 (Risk Management)
• ISO 14155:2020 (Clinical Investigations)

Guidance Documents

• MEDDEV 2.7/1 Rev. 4 (Clinical Evaluation: A Guide for Manufacturers and Notified Bodies)
• MDCG 2020-6 (Clinical evidence needed for medical devices previously CE marked under Directives 93/42/EEC or 90/385/EEC: A guide for manufacturers and notified bodies)
• MDCG 2020-7 (Post-market clinical follow-up [PMCF] Plan Template: A guide for manufacturers and notified bodies)
• MDCG 2020-8 (Post-market clinical follow-up [PMCF] Evaluation Report Template: A guide for manufacturers and notified bodies)
• MDCG 2019-9 (Summary of safety and clinical performance: A guide for manufacturers and notified bodies)

Key Takeaway

MDR compliance transcends document creation. It is about building a coherent, evidence-based narrative weaving together quality management, risk analysis, clinical data, and post-market vigilance into a single, compelling story of your device’s safety and performance. Using this comprehensive checklist to perform a final, critical gap analysis ensures your story is not only complete but also clear, consistent, and readily verifiable, paving a smoother path to successful CE marking under the MDR.

Contact us today for a consultation with our medical devices team.

Clinical development for medical devices is a complex and continuous process under Regulation (EU) 2017/745 (MDR), requiring robust clinical evidence to demonstrate safety and performance. Regardless of whether your product is a novel technology or an updated version of an existing device, regulators demand comprehensive evaluation across every phase. This guide walks you through the key steps, from early strategy to final submission, to help you achieve MDR compliance.

Step 1: Strategy & Planning – Building the Foundation

To begin with, this phase is critical for defining the scope, evidence routes, and overall resource allocation for your clinical efforts. A well-constructed strategy at this stage prevents costly errors and oversights, setting the trajectory for a successful submission. As a result, this phase produces the clinical evaluation plan (CEP), your core strategic document.

Key strategic actions:

Comprehensive gap analysis: Assess all existing data against the MDR requirements applicable to your device’s risk class and intended purpose. This includes preclinical data (biocompatibility, electrical safety, software validation, usability engineering) and potential sources of clinical data.

Defining the evidence route map: Decide if conformity with the general safety and performance requirements (GSPRs) set out in Annex I of the MDR can be demonstrated through existing data or if a new clinical investigation is required.

• Waiver of clinical data: Under MDR Article 61(10), a justification for omitting clinical data may be possible if deemed “not appropriate.” This is reserved for low-risk devices where safety and performance can be demonstrated through comprehensive preclinical testing (e.g., bench testing, non-clinical performance evaluation). You must justify the waiver through risk management and support it with clear technical documentation.
• Clinical investigation route: For novel devices or when equivalence cannot be sufficiently proven, a new clinical investigation is unavoidable, especially for Class IIb implantable and all Class III devices.
• Equivalence route: Alternatively, if you rely on data from another device, you must provide rigorous proof of technical, biological, and clinical equivalence as per the MDR’s strict criteria. Notified Bodies (NBs) apply these requirements strictly, which makes this path to clinical evidence more difficult.

Developing the Clinical Development Plan (CDP): This overarching document integrates pre-market and post-market clinical activities, ensuring a seamless transition from pre-market approval to post-market surveillance.

Using the CEP as the roadmap:

The CEP must define the device and its intended purpose. It should also establish specific clinical safety and performance objectives that are aligned with the device’s intended clinical benefits and risk profile. It must outline clear clinical questions, list relevant data sources, and explain the literature search strategy. A well-crafted CEP is the strategic backbone of clinical development for medical devices, ensuring your evidence generation aligns with MDR expectations.

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Step 2: Investigation & Execution – Generating Robust Data

While the clinical evaluation identifies evidence gaps, a clinical investigation may be required to generate the data needed to address them.

Clinical investigation set-up and conduct:

• Investigation plan and protocol development: You must ensure the protocol is scientifically rigorous and ethically sound, in line with ISO 14155:2020. It should clearly define endpoints, sample size, and study methodology.
• Navigating regulatory approvals: Secure necessary approvals from Competent Authorities and favourable opinions from Ethics Committees in each target member state.
• Trial conduct, monitoring and oversight: Additionally, ensure all sites are adequately trained and monitored in study procedures. Use robust data systems to ensure data integrity and accuracy.
• Vigilance and Safety Reporting: Establish clear processes for capturing, assessing, and reporting all adverse events and device deficiencies in accordance with regulatory timelines. You must ensure these processes comply with MDR requirements, particularly Articles 80–89 and Annex III Section 1.1(c). In addition, where applicable to clinical investigations, compliance with ISO 14155:2020 is also required.

Step 3: Analysis & Clinical Evaluation – Synthesising Data into Evidence

At this stage, you must transform raw data into compelling evidence. The data must be critically appraised, synthesised, and contextualised within the current state of the art.

Understanding clinical data:

Per MDR Article 2(48), clinical data are information concerning safety or performance of a device that are generated from the use of a device, and are sourced from one or more of the following:

• Clinical investigations of the device under evaluation (DuE).
• Clinical investigation(s) or other studies reported in scientific literature, involving a device for which equivalence to the device in question can be demonstrated.
• Peer-reviewed scientific literature reporting other clinical experience with the device in question or with a device for which equivalence can be demonstrated.
• Clinically relevant information from post-market surveillance (PMS), particularly post-market clinical follow-up (PMCF).

Core components of data analysis and compiling the clinical evaluation report (CER):

• Systematic literature review and data appraisal: Execute the literature search as defined in the CEP. The process must be fully transparent, systematic, and reproducible. Evaluate each data source critically for validity, quality, and relevance—whether from your study or existing literature. Standardised appraisal tools should be used to assess the risk of bias and the strength of the evidence.
• Demonstrating conformity with GSPRs: You must clearly link your clinical evidence to the GSPRs in the CER. It should clearly state how the collected data verifies that each applicable clinical requirement is met.
• State-of-the-art comparison: Compare your device’s performance, safety, and benefit-risk profile against the current standard of care and available alternatives. This contextualises your device’s value within the medical landscape.
• Writing a comprehensive and well-structured CER: The final report should clearly justify the device’s clinical safety and performance. It must affirm that the overall benefit-risk conclusion is favourable for the intended target population and clinical setting. Your evaluator(s) must sign the CER to confirm responsibility, and all data, appraisals, and conclusions must be traceable.

Synthesising data into a Clinical Evaluation Report (CER) is a critical milestone in clinical development for medical devices, connecting raw data to a clear regulatory conclusion.

Step 4: Lifecycle Management – Closing the Loop and Ensuring Continuity

Under MDR, clinical evaluation is a continuous process. In fact, certification is not the finish line—it’s the midpoint of an ongoing cycle of evidence generation.

Ongoing post-market obligations:

• PMS: Proactively collect and evaluate real-world data from various sources, including user feedback, complaint handling, literature screening, and registries. This system helps detect emerging risks or performance issues.
• PMCF studies: Where required by the risk profile or as outlined in the CDP, conduct targeted PMCF studies to investigate the long-term performance and safety of the device, or to address any residual uncertainties from pre-market clinical evaluation.
• CER updates: Treat the CER as a living document. Therefore, update it annually for Class III and implantable devices, or every 2–5 years for lower-risk classes. An immediate update is warranted upon the discovery of significant new information that could impact the benefit-risk assessment, such as newly available clinical data, emerging risks, or advancements in the state-of-the-art.

Navigating Challenges

• Data quantity and quality: Data must be sufficient for statistical significance and come from reputable sources. Manufacturers must demonstrate a thorough search of relevant databases (e.g., PubMed, EMBASE) and a critical appraisal of the data’s scientific validity.
• Justifying a waiver: However, waiving clinical data is risky. You must justify it scientifically and ethically, rooted in strong risk management
• Proving equivalence: The bar for demonstrating technical, biological, and clinical equivalence is high. Because NBs assess equivalence strictly, a new clinical investigation is often the better option.

Supporting Documents and Guidance

Regulations

• EU MDR 2017/745

Harmonised Standards:

• ISO 14155:2020 (Clinical investigation of medical devices for human subjects — Good clinical practice)

Guidance Documents:

• MEDDEV 2.7/1 Rev. 4 (Clinical Evaluation: A Guide for Manufacturers and Notified Bodies)

• MDCG 2020-13 (Clinical evaluation assessment report template)

Key Takeaway

Successful clinical development for MDR compliance is not a series of isolated tasks but an integrated, lifecycle-spanning process with clinical evaluation as its continuous core. To sum up, by planning strategically with a thorough gap analysis and a robust CEP, executing clinical investigations with rigor, synthesising data into compelling evidence in the CER, and embracing the ongoing cycle of PMS and CER updates, you demonstrate more than just compliance. You build and maintain a strong, evidence-based case for your device’s enduring value, safety, and performance in the marketplace.