MDR Technical file, and all it's layers...
A medical device Technical File is a summary document prepared by a manufacturer in a clear, well-organised, readily-searchable, and unambiguous manner to demonstrate the safety and performance of a specific device. Regardless of a device class, or its intended use, design, or even the safety history of the device; the manufacturer must have – and keep up-to-date – this technical documentation in order to demonstrate the compliance with general safety and performance requirements of the legislation.
The MDR Technical File template must be completed and submitted to a Notified Body (NB) or a Competent Authority for review and approval. It should be made in English, or in an official language of an EU Member state; and be made available on request for the whole life cycle of the medical device (five years for low risk; and 16 years for high-risk medical devices). Importantly, non-EU manufacturers must keep the file with an authorised representative in the EU for consult whenever requested – as such, keep a controlled version of the file always on hand.
According to Annex II of the EU MDR 2017/745, a medical device technical file should include the following sections:
- Device description and specification, including all the variants and accessories
- Complete labelling and packaging information, including single-unit sales and transport packaging in case of specific management conditions
- Instructions for use in all the languages accepted in the Member States where the medical device is foreseen to be sold
- Design and manufacturing information, such as design schematics and data about all sites, where design and manufacturing activities are performed
- Documentation demonstrating compliance with all general safety and performance requirements and all relevant harmonised and non-harmonised standards
- Benefit-risk analysis and risk management file
- Product verification and validation report, and other relevant documentation
- Pre-clinical and clinical data, such as test results, Clinical Evaluation Report (CER) and Post-Market Clinical Follow-Up (PMCF) evaluation plan
- Post-Market Surveillance (PMS) plan and report
- Declaration of Conformity
In the Device description and specification section, the manufacturers now need to make a reference to the basic Unique Device Identification-Device Identifier (UDI-DI), which will also need to be placed on the label of the device and on all higher levels of packaging. On top of that, specifications exist regarding the UDI-DI in case of reusable surgical instruments, or implantable, so that this code number is easily accessible in all situations.
In the case of Single Use Devices (SUDs), specifically in the risk management documentation, manufacturers shall demonstrate and substantiate why the device is manufactured as such – that is, it should clearly be stipulated why the device cannot be reprocessed.
Another technicality is that for all classes of medical devices, manufacturers must now provide, as per Annex II, information in the technical documentation to explain the design stages and procedures that applied to their device. Before, only Class III devices would have such request, while now all devices are in the same boat in this regard.
In the Device description and specification section, the manufacturers now need to make a reference to the basic Unique Device Identification-Device Identifier (UDI-DI), which will also need to be placed on the label of the device and on all higher levels of packaging.
On top of that, specifications exist regarding the UDI-DI in case of reusable surgical instruments, or implantable, so that this code number is easily accessible in all situations.
Review Process by a Notified Body (NB)
For conformity assessment, the NB needs to review the technical documentation according to the device classification. Importantly, medical devices are assessed by the NBs on a risk-based approach, as such benefits must outweigh the risks, or risks need to be reduced as far as possible and acceptable in light of the current state-of-the-art and over the validity period of the granted certificates. Class III implantable devices, Class III devices, Class IIb implantable devices (with some exceptions), or Class IIb active devices are assessed individually for every device. All other class IIb devices are assessed for at least one representative device per generic group; while, Class II are judged for at least one representative device for each category of devices. In the meantime, Class I devices which are placed on the market in sterile condition, have a measuring function or are reusable surgical instruments, are evaluated only to those specific features of the device, e.g., sterility, measurement or re-use. For all other Class I devices, NBs are not involved in conformity assessment; and manufacturers can declare the conformity of their products, by issuing the EU declaration of conformity referred to in Article 19“3. The NBs or Competent Authorities will carefully examine the submitted application; and, when required, will perform further testing in proper facilities, or request additional evidence from the manufacturer. In the case where the clinical evidence is based on data from medical devices claimed to be equivalent to the device under appraisal, the NB experts will assess the suitability of using such data and document its conclusions on the claimed equivalence, and document the outcome of the conformity assessment in the clinical evaluation assessment report. If the medical device conforms to the relevant requirements, then the NB will issue an EU technical documentation assessment certificate and give its approval to market.
Many manufacturers ask me: "Is there big difference from the Technical File submitted before the MDR?".
The answer is that even though the total number of documents to be included into the technical documentation remains broadly the same; the major difference is the inclusion of a PMS (Post-Marketing Surveillance) Plan, and a Periodic Safety Update Report (PSUR, for devices greater than Class I, Article 86) or a PMS Report (for devices of Class I, Article 85). In the view of the regulators, manufacturers should play an active role during the post-market phase by systematically and actively gathering information from post-market experience with their devices, in order to update their technical documentation and co-operate in the vigilance and market surveillance activities. The relevant data and information gathered through PMS, as well as the lessons learned from any implemented preventive and/or corrective action, should be used to update the technical documentation, such as those relating to risk assessment and clinical evaluation; and, furthermore, should also serve the purpose of transparency. Together with the PMS activities and reports, the major change in the technical file is that the expected quality of the technical documentation has increased substantially; especially, when it comes to clinical data, which now needs to be robust enough to duly substantiate any claims. Most importantly, manufacturers need to improve the scientific quality and intelligibility of their technical documentation, so they can have a continuous approval to market.
The next question commonly asked is: "How different is the PMS under MDR?"
Essentially, medical device manufacturers must document and demonstrate conformity to the General Safety and Performance Requirements (GSPRs), which must be updated in response to PMS activities. Article 2 (60) defines manufacturers are now required to update their PMS system proactively in a comprehensive and systematic fashion as one of the MDR general obligations. The requirements for PMS should be directly proportional to the risk associated with the device, allowing a corrective/preventive action by the manufacturer. This act should be proportionate to the device type and updated clinical evaluation. This means that a strong PMS programme must deliver a broad Real-World Data (RWD) past the confines of a re-market trial though a Post-Market Clinical Follow-Up (PMCF). This programme should detect early problems and guarantee counteractive actions, which are done with a continuous scrutiny on the device long-term performance. Importantly, all of these actions should add value beyond compliance and build a strong sense of trust in the medical device.
And, "What is exactly is Post-Market Clinical Follow-up (PMCF)?"
PMCF is one of the elements of PMS activities that can take the form of a clinical study, an appropriate registry, a customer survey, or even a planned follow-up questionnaire with patients that have used the device. It is tailored to each specific device, and ensures the clinical performance and safety of the device, confirming the continuous appropriateness of the risk upon usage. This is a pro-active measure by the manufacturer focused on a certain area of the medical device performance or safety, with certain pre-approved outcomes or acceptance criteria. These measurements are driven from risk management, Clinical Evaluation Reports (CER) or new PMS data from real-world clinical use. PMCF is particularly important if there is limited clinical data for a legacy device upon CE market approval; or if there are long-term data gaps, or unanswered questions, associated to certain indications, or novel features of a new medical device. For these reasons, it is important to select appropriate PMCF end-points and statistical rationales that bridge any gaps in clinical evidence. The point is to continuously demonstrate a favourable benefit-risk profile of the medical device throughout its expected lifetime.
Furthermore, "Do we need to update the CER?".
Point 74 in the prologue of the EU MDR is clear as water on this one: yes, of course. All relevant data and information gathered through PMS, as well as lessons learned from any implemented preventive and/or corrective actions, should be used to update any relevant part of technical documentation, such as those relating to risk assessment and clinical evaluation reports (CERs). On top of that, section 6.2.3(b) of Annex XIV clarifies that PMS data need to be evaluated for information that has a potential to change the evaluation of the risk/benefit profile, and the clinical performance and clinical safety of the device. This data is required to be fed into the clinical evaluation process in a timely manner, as such clinical evaluation report must be actively updated with data obtained from post-market. A good way to do this is to add tables highlighting serious adverse events, and include commentaries on whether these could have been predicted based on the mode of action of the device. Also, any Field Safety Corrective Actions (FSCA) should be reported, as any reportable events or recalls. How much data to include, of course, goes to the discretion of the manufacturer, but the objective is to promote trust in the product, so transparency is a must.
In addition to the technical file, medical device manufacturers must establish, document, and implement a proper Quality Management System (QMS) and maintain its effectiveness throughout the lifecycle of the devices concerned. Manufacturers should establish a comprehensive PMS system, which is set up under their QMS, and based on a PMS plan. This will provide transparency and safety to market, and hopefully fewer problems for the manufacturers in the future. The motto of the new technical file and MDR should be seen as basically ‘prevention is better than the cure’.
By keeping an eye on post-market surveillance, and updating the technical file promptly and regularly with a strong quality management system, manufacturers will be practicing the fundamental principles of modern health care and helping to support a healthier society.
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