By Marcelo Trevino, Agendia
The first article in this two-part series covered details associated with economic operator responsibilities, overall QMS considerations, and common challenges during implementation of the EU’s Medical Device Regulation (MDR) and the EU’s In Vitro Device Regulation (IVDR). This article focuses on typical challenges experienced during the technical documentation assessments conducted by the notified bodies.
It is common for organizations to have many legacy devices with long histories under the previous medical device or in vitro diagnostic directives that may have undergone many changes or company acquisitions. Because EU MDR and EU IVDR do not allow grandfathering, all new requirements – including additional information that must be gathered and new required testing – must be presented and explained clearly for the notified body technical reviewers who will be analyzing evidence of compliance in detail. Therefore, proactive preparation is crucial.
Common challenges and key aspects to consider before and during the technical documentation assessments include:
- Tests that were leveraged shall be adequate to comply with current requirements.
- New general safety and performance requirements (GSPRs) that were not in place when the tests or devices were initially launched must be addressed. A GSPR checklist is required and files should provide clear conclusions. The requirements and evidence shall be clearly organized within the technical file (clear data and clear reports).
- Procedures, plans, and templates must be in place even while some EU provisions are not ready, including a plan to monitor the publication of guidance documents and plans in place for implementing all applicable requirements.
- Harmonized standards or common specifications need to be adequately referenced in all applicable documentation, and organizations shall have a system in place to stay up to date with any new revisions to these standards and specifications.
- If a performance evaluation plan covers multiple devices, a conclusion of conformity should cover all devices included in the plans and reports.
- Clinical evidence must be available for all legacy devices and data can be obtained from different sources, such as, for example, clinical performance studies, scientific peer-reviewed literature, and published experience gained by routine diagnostic testing. The clinical performance studies shall be linked to the plan for post-market performance follow-up.
- Evidence of the person responsible for regulatory compliance having oversight of the Summary of Safety and Clinical Performance (SSCP) should be readily available.
- Linkage and consistency between the information in declaration of conformity, the Clinical Evaluation Report, the instructions for use, the SSCP, and risk management shall be established.
- Residual risk linkage between adverse events and potential complications shall be included in the instructions for use.
- A complete set of labels and instructions for use in all the languages accepted in the Member States where the device or tests will be sold shall be available for review.
- The SSCP should reflect performance evaluation and must be updated at least annually for class III and implantable devices. This is also a new requirement for in-vitro diagnostic class C and class D devices; therefore, the guidance document MDCG 2019-9 should be carefully reviewed.
- Evidence confirming that the manufacturer has verified that the portions of the SSCP intended for patients can be read and understood by a person without professional or specialized knowledge in the test or device shall be available.
- A device-specific post-market surveillance plan and post-market clinical follow-up plan (if applicable) shall be available. Manufacturers need to demonstrate these elements are designed to proactively collect and evaluate data.
- Manufacturers of class I devices shall prepare a post-market surveillance report summarizing the results and conclusions of the analysis of the post-market surveillance data gathered as a result of the post-market surveillance plan, including CAPAs taken and evidence that the report is updated as needed. The report shall be available to the competent authority upon request.
- A risk management plan shall be established and documented for each device.
- Evidence showing implementation of incoming, in-process, and final inspections and the results of those inspections should be available for each device.
- A clinical evaluation plan as well as a clinical evaluation report (CER) shall be available for each device.
- Design and manufacturing requirements from GSPRs require procedures to be described in the instructions for use addressing safe disposal of the device and related waste substances by the user patient or other person.
- For MDR: Class III medical device implants or IIb medical devices that administer medicines shall undergo additional clinical evaluation requirements that should be in place prior to certification.
- Compliance with all applicable MDCG guidance documents for all the devices subject to certification (some guidances are still in process of being released) will be necessary. The latest MDCG endorsed documents are here.
Requirements are more explicit and prescriptive with respect to what data should be gathered, how it should be gathered, and how it should be used. Even a declaration of conformity must follow requirements identified under Annex IV. Without proper organization, device manufacturers must spend a significant amount of time explaining different versions and justifications, which only slows down the process.
An overview of the technical documentation is provided below; each organization should check Annex II of MDR and IVDR to ensure all requirements are fully addressed and structured appropriately for the notified bodies in their technical documentation. It is also important to review submission guidelines provided by each notified body, which can greatly help to align on expectations.
- Legal manufacturer
- Authorized representative within the EU if applicable
- Trade name of the device
- Existing certification
- Declaration from the manufacturer stating that no application has been lodged with other notified body
Description and specification of the device, including variants and accessories
- Intended purpose of the device
- Description of the assay method
- Class of the device and rationale
- Description of the device and its components and specifications
- Use of specimen (if applicable)
- Instrumentation of automated assays
- Description of accessories and combinations
- Reference to previous and similar generations of the device
- History of changes since placing on the market or last evaluation according to regulation (if applicable)
Information to be supplied by the manufacturer
A complete set of labels and instructions for use in the languages accepted in the Member States where the device will be sold.
Design and manufacturing information
General safety and performance requirements
Summary table of Annex I requirements
Benefit-risk analysis and risk management
Risk analysis and risk control methods, including risks associated with usability
The documentation shall contain information on:
(a) the benefit-risk analysis referred to in Sections 1 and 8 of Annex I, and
(b) the solutions adopted and the results of the risk management referred to in Section 3 of Annex I.
Product verification and validation
The documentation shall contain the results and critical analyses of all verifications and validation tests and/or studies undertaken to demonstrate conformity of the device with the requirements of the regulations and, in particular, the applicable general safety and performance requirements.
Preclinical and clinical data and additional information required in specific cases per Annex II
Information on analytical performance, clinical performance, and clinical evidence according to Annex XIII of Regulation (EU) 2017/746.
- Performance evaluation plan
- Scientific validity report
- Analytical performance report
- Clinical performance report
- Requirements for class D devices
- Requirements for self-testing/near-patient testing devices
- Clinical evidence and performance evaluation report
- Stability studies
- Software verification and validation
- Additional info (if applicable)
- Draft of the summary of safety and performance
- Post-market surveillance plan
- Post-market surveillance data
For MDR: The technical documentation on post-market surveillance to be drawn up by the manufacturer in accordance with Articles 83 to 86
For IVDR: The technical documentation on post-market surveillance to be drawn up by the manufacturer in accordance with Articles 78, 79, 80, and 81
EU declaration of conformity
The EU declaration of conformity shall contain all the following information:
1. Name, registered trade name or registered trademark and, if already issued, SRN as referred to in Article 31 (MDR) and Article 28 (IVDR) of the manufacturer and, if applicable, its authorized representative, and the address of their registered place of business where they can be contacted and their location can be established;
2. A statement that the EU declaration of conformity is issued under the sole responsibility of the manufacturer;
3. The Basic UDI-DI as referred to in Part C of Annex VI;
4. Product and trade name, product code, catalogue number, or other unambiguous reference allowing identification and traceability of the device covered by the EU declaration of conformity, such as a photograph, where appropriate, as well as its intended purpose. Except for the product or trade name, the information allowing identification and traceability may be provided by the Basic UDI-DI referred to in point 3;
5. Risk class of the device in accordance with the rules set out in Annex VIII;
6. A statement that the device that is covered by the present declaration is in conformity with the applicable regulation and, if applicable, with any other relevant Union legislation that provides for the issuing of an EU declaration of conformity;
7. References to any common specifications used and in relation to which conformity is declared;
8. Where applicable, the name and identification number of the notified body, a description of the conformity assessment procedure performed and identification of the certificate or certificates issued;
9. Where applicable, additional information;
10. Place and date of issue of the declaration, name and function of the person who signed it, as well as an indication
The assessment of technical documentation involves a detailed analysis by the notified body’s technical reviewers. Data organization is a key element of a successful technical review. The new regulations address the need for this information to be presented in a clear, organized, readily searchable, and unambiguous manner, in a form that can be easily consulted. Technical information is subjected to a preliminary review to verify its content and identify the points to be completed before an assessment is initiated. The assessment is then planned based on the results of this review.
Annex II and Annex III provide a correlation of the required documentation; having information clearly organized to explain all the testing that was performed, including the equivalence of clinical data obtained at different times and all the verification and validation activities associated with each device will help reduce review times and cost.
While this could be particularly challenging for many legacy devices, most companies can contribute to a smooth transition to the new regulations by establishing a standard process to provide all the required information to their notified bodies and by implementing their guidance recommendations.
About The Author:
Marcelo Trevino is the global vice president, regulatory affairs and quality assurance at Agendia, a molecular diagnostics company focused on breast cancer genomic testing. He has more than 25 years of experience in quality and regulatory affairs, serving in senior leadership roles with different organizations while managing a variety of medical devices: surgical heart valves, patient monitoring devices, insulin pump therapies, surgical instruments, orthopedics, and medical imaging/surgical navigation, amongst others. He has an extensive knowledge of medical device management systems and medical device regulations worldwide (ISO 13485:2016, ISO 14971:2019, EU MDR, EU IVDR, MDSAP). Trevino holds a B.S. in industrial and systems engineering and an MBA in supply chain management from the W.P. Carey School of Business at Arizona State University. He is also a certified Quality Management Systems Lead Auditor by Exemplar Global. He can be reached at: firstname.lastname@example.org or on LinkedIn.