With less than one month remaining for the transition to the Medical Device Regulation (MDR), this article takes a look at the key areas to be addressed for manufacturers selling medical devices in Europe.
#1. Update Quality Management System (QMS)
Given the new MDR requirements will have an impact on the existing process and procedures in the quality system on various aspects, allocating adequate resources to align a quality management system (QMS) with the new MDR regulations while assessing and implementing changes to comply with ISO 13485:2016 will facilitate a smoother and timely transition from the Medical Device Directive (MDD) to the MDR.
Under the new MDR requirements, the following procedures are likely to be affected:
- Premarket regulatory procedures, e.g., classification rules, regulatory pathways, general safety and performance requirements/templates, requirements for local representatives.
- Procedures for planning, preparation and submission of the technical files and device entry to the European databank on medical devices (Eudamed).
- Clinical evidence.
- Risk management procedures, e.g., a risk management plan.
- Postmarket regulatory procedures: e.g., postmarket surveillance (PMS) plans and reports, periodic safety update reports (PSUR), and summary of safety & clinical performance (SSCP).
It is also important to note that the PMS activities, one of the major focuses of the MDR, impose some of the most significant impacts on relevant QMS records, including clinical evaluation report (CER), risk management, instructions for use (IFU) and labelling. Hence the interconnection between all QMS processes must be reviewed across business departments to ensure consistency between QMS records and postmarket data collected is performed as required by the new regulations. If implemented properly, the new regulatory environment will provide companies the opportunity to move beyond compliance to quality and enhance products through improved patient safety, performance outcomes and customer satisfaction.
#2. Review Product Classification and Conformity Assessment Routes
All manufacturers should assess whether the new classification rules impact their devices already on the market or devices anticipated to be on the market in the future. For up-classified products, additional resources will be required to fill the gap as there will be substantial changes in conformity assessment procedures, including more frequent reviews by the Notified Bodies (NB). Products that may need to be re-certified in a different, often higher risk class include:
- Devices incorporating nanotechnology.
- Orthopaedic implants such as spinal disk replacements or implants that come in contact with the spinal column.
- Reusable surgical instruments.
- Life-saving active therapeutic devices such as closed-loop systems and automated external defibrillators; and
- Software (standalone software will no longer be classified as active medical device).
Other changes in the “definition” chapter also impact on the conformity routes for the following product types:
- “Accessories” now cover products specifically or directly assisting another device in its intended purpose;
- Custom-made devices exclude products that are mass-produced by means of industrial manufacturing processes, and;
- Inclusion of products derived from human cell or tissue derivatives.
The new regulatory requirements also mandate a risk profile similar to medical devices for products without an intended medical purpose, such as cosmetic implants, contact lenses and cosmetic laser products (Annex XV). Also new to the MDR is the inclusion of the Common Specifications (CS). These are drawn up for cases where no sufficient harmonized standards are available. Manufacturers of the products captured in Annex XV can adopt the design requirements in the CS to prepare their technical documentation.
#3. Re-Evaluate Clinical Evidence
The MDR brings forth new requirements to clinical evaluation and clinical investigation, including a mandatory post-market clinical follow-up (PMCF) to collect quality, performance and safety data throughout the product life cycle. As compliance with the current MDD on clinical evidence is unlikely to meet the requirements under the new rules, manufacturers should perform a gap analysis to determine the impact of the new clinical investigation requirements on the existing clinical investigation for new devices. Device makers should also conduct a thorough assessment to identify gaps in clinical evidence compiled for existing approved products.
The PMCF data is required for high-risk devices where long-term safety and performance data is unknown or where European Commission (EC) certification is based on equivalence. For devices where long-term outcomes are available, manufacturers can provide justification without a PMCF. A summary clinical evaluation is also required to be validated by the NB and published by Eudamed for Class III and implantable devices.
In cases where a clinical evaluation has been performed based on equivalency data, manufacturers need to ensure they have access to the equivalency data of other manufacturers by way of establishing agreements with other manufacturers. If the equivalence data is unlikely to be accepted in the future, conducting one’s own clinical trials should be considered.
#4. Talk to Your Notified Body (NB)
Manufacturers must assess the potential of their existing NB as they may not be redesignated or may not be able to support the same scope of products post MDR. It is crucial to discuss with the current NB and understand if they can meet the new requirements in a timely manner. If the re-notarization process is likely to cause long delays, alternative plans and transition procedures should be put in place, potentially including a change of the manufacturer’s NB.
#5. Revisit Post-market Surveillance (PMS) Procedures
All manufacturers will be required to comply with PMS requirements in the MDR after May 26, 2020, regardless of whether an EC certification for a medical device is issued under the MDD or the MDR.
The PMS system consists of procedures that control the PMS activities, plan, reports and PSUR. PMS activities should cover market feedback, customer feedback and complaints, vigilance, recalls, and collection of new data from published literature and/or databases. As PMS activities have a major impact on various QMS records, it is crucial to ensure consistency and regular updates between different records. For example, PMS data must feed into the CER, and similarly, risk analysis must be in line with adverse events/rate collected in the PMS data and CER. Manufacturers for implantable and Class III devices are also required to submit the SSCP which includes information on therapeutic alternatives, CER summary, and the list of residual risks or undesirable side effects to the NB. The MDR requirements, device class, and frequency of updates are summarized in the following table:
#6. Identify Roles and Responsibilities
The MDR adds responsibilities and obligations to all economic operators in the supply chain, including manufacturers, importers and distributors, and therefore it is important that each role understands and fulfils the new requirements. Additional responsibilities for importers and distributors include:
- Verification of the CE mark, EC Declaration Conformity and labelling requirements (importers also a need to keep relevant declaration of certificates and conformity statements).
- Place only conforming devices on the market (importers also need to check registration of device and add its own details in Eudamed).
- Comply with storage and transport conditions set out by manufacturer (importers also need to check compliance with Annex I).
- Inform competent authorities (CA), NB and operators upstream in the supply chain on serious risks, keep records of complaints, non-conforming devices, recalls and withdrawals.
- Inform operators upstream in the supply chain on potential non-conformities and complaints.
- Cooperate in corrective actions and provide samples or access to CA.
- Ensure traceability on economic operators, health institutions, health care professionals supplied with the devices via means of establishing/updating documents such as contracts, written nominations, databases entries as mandated by MDR.
- Distributors also need to register their information in the national database.
Manufacturers need to implement the below changes to fulfil additional obligations:
- Check and update all contractual arrangements with the partners in the supply chain to ensure alignment with the MDR requirements, e.g., clarify liability conditions for local representatives, update SOPs for the implementation of Unique Device Identifiers (UDIs).
With the uncertainty of the current Brexit deal, manufacturers will need to determine the best path to ensure continued supply, including the possibility of identifying NBs and authorized reps outside the U.K. to avoid roadblocks in the future.
Changes brought about by these new regulations are significant and require manufacturers to take proactive action on multilevel activities and decisions on their implementation. The MDR impacts all areas of the business, including supply chain arrangements, regulatory resources and processes including sales and marketing. Understanding the EU MDR requirements and identifying its impact on the business is critical to a successful transition. Manufacturers will need to assess their entire product portfolio and their readiness in the context of the new regulation to prioritize their transition effort.