Postponement of the European Union’s Medical Device Regulation (EU MDR; 2017/745) has left orthopedic device manufacturers considering how best to move forward with compliance as well as understanding how to interpret certain requirements. On July 22, 2020, the Orthopaedic Surgical Manufacturers Association (OSMA) hosted its Summer educational program, bringing together regulatory experts across the orthopedic industry and European Notified Body representatives and expert consultants in a virtual meeting to address the challenges and complexities of meeting MDR’s requirements.
Dario Pirovano, Senior Regulatory Advisor, MedTech Europe, opened the meeting with a discussion of the April 24, 2020 Amendment to the EU MDR (Regulation 2020/561), adopted by the European Parliament and Council to ensure continued availability of medical devices in the EU in response to the COVID-19 outbreak. This amendment postpones the date of application (completion of transition to MDR) by one year (to May 26, 2021), thereby extending the applicability of the Medical Device Directive (MDD; 93/42/EEC) and Active Implantable Medical Device Directive (AIMDD; 90/385/EEC) and also permits certain critical devices to be distributed on an EU-wide basis under a “compassionate use” clause. This amendment, immediately in effect, introduced a number of practical considerations for medical device manufacturers as they execute their MDR compliance plans. Manufacturers placing their devices on the market under MDR before or after May 26, 2021, must comply with all relevant aspects of MDR. Manufacturers may choose to maintain valid MDD/AIMDD certificates through the established grace period (which starts on May 26, 2021 and ends on May 25, 2024). While Notified Body designation to MDD/AIMDD will remain in place for the extended transition period (void on May 26, 2021), it is unknown how many Notified Bodies will remain operational. After May 21, 2021, any “substantial changes” to devices certified under MDD/AIMDD can continue to be made; however, once a “significant change” is made, the device must comply with all MDR requirements. The area of “significant change” continues to require additional definition and guidance for manufacturers as they consider the regulatory impact of making changes for devices already on the market.
MDCG 2020-5: Guidance for equivalence approach
MDCG 2020-13: Clinical Evaluation Assessment Report Template
Guidance and templates for PSURs
Matthias Fink, M.D., Orthopedic and Trauma Surgeon and Clinical Reviewer for TÜV SUD, presented a clinical overview considering the recently published guidance documents by the Medical Device Coordination Group (MDCG). This included the template of the Clinical Evaluation Assessment Report (MDCG 2020-13) the Notified Bodies are required to use. MDCG 2020-5 provides guidance on establishing technical, biological and clinical equivalence to an already marketed device. Under MDR, it will be challenging to establish equivalence to a device that is not owned by
the manufacturer (e.g., competitive device), as contractual agreements permitting access to technical documentation must be in place for all implantable and Class II devices. The MDCG 2020-6 provides guidance on sufficient clinical data for legacy devices. Besides a definition of well-established technologies (WET) the guidance contains a suggested hierarchy of clinical evidence for legacy devices.
These presentations set the stage for an interactive panel discussion during which OSMA members were able to pose direct questions to the Notified Body representatives1 and expert consultants2 and receive relevant and timely information. Panel participants included:
Bassil Akra,2 Ph.D., CEO, QUNIQUE GmbH
Matthias Fink,1 M.D., Orthopedic and Trauma Surgeon, Clinical Reviewer, TÜV SUD
Max Singh,1 Ph.D., Global Director-Orthopedic Focus Team, TÜV SUD
Monisha Phillips,1 Ph.D., Global Head, Orthopedic & Dental Devices, BSI
Marie Abdallah,1 Unit Manager, Non-Active Medical Devices, GMED North America-LNE Group
The following captures highlights from this interactive panel discussion.
Significant vs. Non-Significant Changes
All panelists agreed that additional guidance is needed to define what constitutes a significant vs. a non-significant device change, as this has led to inconsistencies in interpretation among manufacturers and Notified Bodies alike. As significant changes made to an MDD compliance product or quality process trigger the need to comply with all MDR requirements, it is important to be sure that this threshold is well-understood and consistently followed. Significant design or specification changes can occur, for example, when a manufacturer adds a new orthopedic implant size that falls outside the approved range or when design tolerances are broadened. However, the impact of other changes is less clear, such as making certain material changes, which may or may not be significant depending on the impact of the change. All panelists agreed that it is important to speak to your Notified Body in advance of making these types of changes.
Dr. Akra reiterated that all device changes should be individually assessed. He said, “It is important to look at design changes on a case-by-case basis. In general, this can be challenging. Manufacturers need to fully assess the change and try to follow the criteria outlined in the new MDCG guidance, which introduces the possibility of some changes being non-significant. Manufacturers need to provide a clear analysis of the purpose of the change and its impact: Is this a change to the design or intended use? Does the change introduce a new performance claim? Certain changes to the quality management system are allowed, as are design changes related to a supplier but still falling under the same specifications. It is highly recommended to speak to your Notified Body in advance to avoid surprises.”
Dr. Phillips echoed these sentiments. “Keep the communication lines open with the Notified Bodies. We are open to discussions on what constitutes a significant change. Manufacturers should come prepared and follow the decision flowchart in the MDCG guidance. There are lots of changes that can be easily made but some changes will require more discussion, like material changes as to whether they are truly significant or not.”
The panelists were also asked how manufacturers should manage design changes to MDD products or quality processes that trigger compliance to the MDR, particularly when other system components remain under the MDD. For example, can version one of the device live under MDD while version two is pending MDR review?
Dr. Singh noted that specific examples are needed to address why not to improve previous designs. Besides the necessary considerations of risks regarding the latter, there are also economic and portfolio considerations to be clarified individually by each manufacturer.
Dr. Akra clarified by saying, “…based on the legal text, there is no obligation to immediately move from MDD to MDR for one product, and a manufacturer would not be forced to move every device to MDR as long as the MDD certificate is still valid (May 2024 deadline to be considered), and the Notified Body remains certified, but detailed evidence must be presented.”
Dr. Phillips also shared her perspective on this question. “It depends. I would question what the design change is and why it is occurring. For example, if the change represented an improvement, you should ask why you would leave an inferior product on the market. Risk considerations are also important.”
Resolving Differences in Interpretation
An OSMA member asked the panelists about a scenario where a manufacturer may encounter a different or conflicting opinion from Notified Bodies, “which can sometimes be a delicate matter.” Often there is internal debate whether this should be raised to the Notified Bodies. All of the Notified Body representatives on the panel agreed that they would appreciate hearing about such discrepancies when they occur and understanding the basis for other opinions.
Dr. Akra reflected, “Thirty years after the Medical Device Directives, we are still discussing the interpretation of the requirements. We all are still in the learning phase – Member States, Manufacturers and Notified Bodies – and interpretations are moving in a different direction each day. We are still learning from each other, and there are multiple ways to fulfill the same text of the Directive and requirements. We need to create a combined learning and be transparent, ensuring no discrepancies on expectations.”
Dr. Phillips further emphasized, “As Notified Bodies, we strive to be consistent and would welcome feedback. We want to ensure we are being consistent, and raising these discrepancies can identify the need for future guidance.”
Ms. Abdallah added, “Everything boils down to the manufacturer’s justification. It needs to be solid. Our experience is that manufacturers are already raising areas of discrepancy in opinion.”
Several panelists referenced the successful spinal devices classification paper (Team NB - Joint NB Position Paper on Spinal Classification per the MDR, issued December 2018) as an excellent example of collaboration between manufacturers and Notified Bodies. OSMA was a major contributor to the proposed classifications which were carried forward into this position paper. This serves as a model for future efforts to provide consistent interpretation and guidance in areas that may still be open to different opinions.
Common Deficiencies During Technical Documentation Review
When asked about where the Notified Bodies are seeing common deficiencies, the panelists offered the following watch-out areas:
- Clinical (equivalence and data)
- Biological safety
- Incorrect classification
- Inadequate manufacturing documentation and verification and validation documentation
- Use of appropriate CMD codes
One topic that continues to be the subject of considerable discussion and challenge is determining what constitutes sufficient clinical data. Dr. Fink addressed this question by saying, “There is no easy answer to that. The determination is always a case-by-case decision and is based on many different factors.” He went on to further say that “Claiming equivalence to a competitor device will be quite impossible.” This is because the MDR requires continuous access to a competitor’s technical documentation that is often considered proprietary.
As for device classification, Dr. Phillips advised, “Keep conversations going with your Notified Bodies to understand devices and their classification to enable consistent classification and appropriate grouping.”
For legacy devices (devices that are CE Marked under the current Medical Device Directive) and MDD-certified devices placed on the market during the grace period, manufacturers are advised to closely follow the General Safety and Performance Requirements (GSPR) checklist (Annex I, MDR). Our panelists offered the following helpful comments:
Dr. Singh said, “TUV SUD expects a table to show linkage between the requirements and the associated documents. Although one requirement includes to provide the Technical Documentation in an organized, clear, and unambiguous manner, not every manufacturer provides a link to the referenced documents.”
Dr. Akra said, “The technical documents should be readable and searchable and include a checklist with hyperlinks to supporting documents. Manufacturers need to write the technical documents in a way that reviewers can easily locate documents.”
Hazardous Materials Classified as Carcinogenic, Mutagenic, Reprotoxic (CMR)
The panel discussion shifted toward MDR requirements pertaining to devices containing materials classified as Carcinogenic, Mutagenic or Reprotoxic (CMR), such as cobalt metal. In response to questions from several industry representatives, the panelists shared the following considerations:
Dr. Akra said, “It is important to understand the regulation and apply it correctly. General safety and performance requirements are not prohibiting the use of these substances, but a clear justification must be provided, demonstrating an acceptable risk/benefit profile when compared to the current state of the art. Manufacturers must show the Notified Bodies the evidence and how the CMR material adds benefit or value. The manufacturer must also disclose if the threshold amount (0.1% w/w) is exceeded.”
The Notified Body panelists reinforced these comments, emphasizing the importance of taking a risk-based approach and justifying devices containing CMR materials. As with all other material changes, if a material change is made, a clear description and justification will be needed for why it is acceptable to keep the old device on the market still. An observation was raised that some manufacturers are experiencing delays (from suppliers) in CMR assessments and whether it is possible for the technical documentation to be placed on hold? While this is possible, manufacturers should align expectations with their Notified Body on when the assessment will be completed; otherwise, they may run the risk of delays due to competing Notified Body resources and priorities.
The EU MDR poses significant regulatory obligations for legal manufacturers, importers and distributors. Each economic operator is independently responsible for verifying regulatory compliance and maintaining required records and is subject to unannounced audits.
Dr. Akra reiterated these obligations. “The MDR is very clear on the obligation of economic operators. There are no exemptions. Every economic operator must satisfy the MDR requirements. They must have agreements in place between each other that define how requirements are met and who does what. Sampling of documentation is possible but it must be justified, defined and followed in an established quality management system.”
Manufacturers must assess supplier performance and define the criticality of suppliers, even those of raw materials and semi-finished goods, based on relative risk to the medical device. All links should comply with ISO 13485, and an on-site audit of the supplier by the Notified Body may be required.
Notified Body Priorities
When asked about their respective priorities in the coming year, the panelists offered the following insights.
Dr. Phillips noted, “…this year will be a completely different year than last year. BSI will place priority focus on certificate renewal completions and Article 120 significant changes. We will be running a parallel stream of MDD and MDR reviews, MDR first come-first served, giving priority to devices with expiring MDD certificates based on expiring certificate date.”
Ms. Abdallah offered a similar focus, placing GMED’s priorities on “…certificate renewal, MDR applications for our client base, significant changes under MDD and Article 120 and MDR new service will be first come, first served.”
Similarly, for TUV SUD, Dr. Singh confirmed a continued priority focus on MDR.
This concluded a lively and informative exchange and highlighted the importance of frequent and meaningful communication between regulators and industry as they together continue to navigate the challenges and complexities of the EU MDR.
Sharon Starowicz is an OSMA Consultant.
The Orthopaedic Surgical Manufacturers Association (OSMA) is a nonprofit organization whose membership consists solely of manufacturers of orthopedic surgical appliances, implants, instruments or equipment and orthobiologics. Since its inception in 1954, OSMA has continued to actively participate in standards and regulatory guideline development; educate our membership on regulatory matters and provide regulatory professionals a forum to collaborate, communicate, cooperate and interact with worldwide regulatory agencies and health care professionals on issues to improve the application of device law and promote collaborative interaction for appropriate regulation.