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Regulatory Focus™ > News Articles > 2019 > 10 > Regulatory Strategies for EU MDR and EU IVDR Implementation

Regulatory Strategies for EU MDR and EU IVDR Implementation

Posted 03 October 2019 | By Gloria Hall 

Regulatory Strategies for EU MDR and EU IVDR Implementation

September feature articles took an in-depth look at the new EU Medical Devices Regulation (MDR) and In Vitro Diagnostic Regulation (IVDR), where global medical device leaders explored the nuances of the new requirements and answered the industry’s most challenging questions. Individual articles covered the implementation of the regulations into national legislation, what the new regulations mean for substance-based medical devices, how to incorporate clinical evaluation requirements into the design and development process, challenges in clinical evaluation for the EU versus China, contractual and QMS-driven implementation of shared economic operator resources, IVDR challenges, UDI and labelling compliance, postmarket surveillance postmarket clinical follow-up and the consequences of a no Brexit deal and fewer notified bodies.

Sufficient Clinical Evidence

Presenting sufficient clinical evidence is an important aspect of the EU’s MDR. European medical device expert, Leo Hovestadt, evaluates what is considered “sufficient clinical evidence” and covers its important place in EU MDR in “What is Sufficient Clinical Evidence According to the MDR?” The author defines sufficient clinical evidence and discusses the kinds of clinical evidence required and what evidence can be considered state-of-the-art. Equivalent devices and benchmark/similar devices are discussed as well as performance studies.

Economic Operators

MDR and IVDR introduce a complete economic operator regime for medical devices. While the old directives replaced by these regulations regulated only the manufacturer and the authorized representative, the MDR and IVDR regulate the importer and the distributor, covering the supply chain up to the end-user. Legal experts, Agnes Szoboszlai and Erik Vollebregt, discuss how the Economic Operators (EOs) under MDR and IVDR can organize themselves and cooperate in such a way that each of their obligations can be fulfilled without unnecessary repetition of action while providing objective evidence of completion and ensuring compliance. In “Implementation of Shared MDR Economic Operator Resources,” the authors suggest how cooperation can be realized, both in the case of internal and external economic operators by using shared resources and tools. They discuss the obligations of manufacturers, authorized representatives, importers and distributors and describe the shared tools which can be either realized by shared quality management systems or agreements.

Stricter Requirements

As a result of sweeping changes in MDR, substance-based devices are among the many devices facing reclassification and additional stringent requirements if they are to remain on the market. Regulatory authorities, Elizabeth Starling and Angela Johnson, provide a brief history of substance-based device regulation in context of the historical borderline medical device framework in Europe. “What EU MDR Means for Substance-Based Medical Devices” also outlines the impact of the MDR transition on CE certification of such devices and provides future perspectives on emerging issues in substance-based device regulation. The authors define substance-based medical devices, look at their regulatory evolution and speculate on what MDR means for the future of substance-based devices.

Nearly all legal manufacturers of medical devices depend on suppliers to manufacture their final product. However, relatively little attention has been given to the ramifications of the application of MDR on the relationship between legal manufacturers and their suppliers and subcontractors. Regulatory strategists, William Enns-Bray and Phillipe Etter, address these concerns in “Impact of Regulation 2017/745 (MDR) on the Relationship Between Medical Device Manufacturers and Their Suppliers and Subcontractors.” The authors propose a “balanced approach” for maintaining compliant supplier quality agreements for the new regulatory landscape. The authors assess the impact of MDR, cover the implications for quality agreements between medical device manufacturers and suppliers and discuss strategies for legal manufacturers achieving compliance with MDR as well as strategies for suppliers achieving compliance with MDR. They conclude that notified bodies will likely attempt to exert more control over suppliers involved in medical device manufacturing, both directly and indirectly through the legal manufacturers while regulatory strategy effectiveness will depend on perception of the requirements.

Current medical device regulations in both Europe and China require that Clinical Evaluation Reports (CERs) be based on Guidelines on Medical Devices (MEDDEV), CFDA Technical Guidelines for the Clinical Evaluation of Medical Device in addition to clinical evaluation requirements contained in MDR. China has attempted to use slightly modified EU guidance for CER submissions; however, although requirements in the guidelines between EU and China may look similar, CERs for China written using EU guidance are always rejected by Chinese authorities. Regulatory specialists, Jasmin Hunter and Michael Yan, explain how to write a CER based on China’s National Medical Products Administration (NMPA) guidance and how to convert and submit existing EU CER requirements for China. In “Challenges in Clinical Evaluation for the EU Versus China,” the authors compare and contrast the process of converting an MDR-compliant CER for submission in China by demonstrating the differences in requirements, outlining specific requirements for China and providing locations to the required information in MDR-compliant documentation. They conclude it is possible to convert an MDR-compliant CER for submission in China if care is taken to add the necessary additional NMPA requirements.

MDR defines the scope and objective of postmarket surveillance within the EU. In “Postmarket Surveillance and Postmarket Clinical Follow-up,” regulatory expert, Adina Chen Bar, explains the difference between postmarket surveillance (PMS) and market surveillance in regard to regulatory compliance. The author discusses PMS planning and reporting, including types of reports, postmarket clinical follow-up and transparency, accountability and documentation burden.

It is essential when reading IVDR to not skip the preamble because it sets the “scene” and the priorities of the EU in writing the regulation, according to IVD expert Sue Spencer. The In Vitro Diagnostic (IVD) Directive was never updated, while the Medical Device Directive (MDD) has experienced a series of gradual changes. In “The Essential IVDR and the Challenges it Presents,” the expert shares her knowledge on the key elements of IVDR, including device classification changes, oversight, clinical evidence and performance evaluation and postmarket vigilance. She cautions about the effects of notified body reductions and the consequences. She concludes by warning that significant changes may impede market launch for some products.

Regulatory Challenges

MDR poses many new questions and provides a variety of challenges for the medical device industry and while there are many regulatory changes, there is little explicit information in MDR for projecting what the impact the regulation may have on the Design and Development (D&D) process. Regulatory leader, Keith Morel, presents a number of regulatory changes in “Incorporating Clinical Evaluation Requirements Into the Design and Development Process Under MDR” and covers several questions important to manufacturers regarding clinical evidence, clinical data, clinical evaluation, clinical safety, clinical performance, clinical outcomes and how they may fit together under new requirements. The author speculates on the impact MDR might have on the design and development process while focusing on the incorporation of the new clinical requirements.

Although the German Federal Ministry of Health initiated National Working Groups (NAKI) to improve the implementation process, MDR and IVDR continue to cause a number of regulatory ‘bottlenecks’ including problems with the European database on medical devices (EUDAMED), a reduced number of Notified Body (NB) applicants, a reduced number of designated NBs to conduct reviews and new and stricter classification rules for these devices. Regulatory strategy experts, Ralf Hess, Dominik Aumer and Simon Schulz, address the issues in “Implementation of IVDR and MDR Into National Legislation,” where they provide a real life example from Germany’s experience and examine the revisions from an implementation perspective. The impact of this new regulatory environment and associated challenges for medical device and in vitro diagnostic device manufacturers are discussed as well as hurdles that could make full implementation difficult.

Unique Device Identification (UDI) is a system for identifying the distribution and use of medical devices, including rules for assigning UDI, the data elements associated with the Device Identifier (DI), the unique number assigned to a specific product) and requirements for the database to contain and control associated data. In “Breaking Down UDI Questions,” global regulatory expert, Lena Cordie-Bancroft, answers questions and clears up ambiguities related to the UDI system developed for medical devices related to US and EU regulations. The author presents an in-depth discussion of terms including base package, unit of use, packaging levels, UDI databases, accessories and spare parts, UDI ownership and scanning versus verifying. She also looks at UDI development outside of the US and EU.

No-Deal Brexit Consequences

MHRA has published guidelines for how medical devices will be regulated in the interim if specific clauses are not arbitrated into an agreement prior to the 31 October Brexit deadline. “In Contingency Plans for MDR and IVDR Implementation for a no Deal Brexit,” senior regulatory specialist, Ashley Clark, discusses implementation of MDR and IVDR and potential exit of the UK from the EU. The author suggests the fate of regulations will be not without consequence should the UK and the remaining members of the EU find they are unable to negotiate how medical devices will be regulated, sold and moved between the UK and the EU if Brexit becomes a reality. She covers implications for a no deal Brexit and how a lack of clear guidance to address this reality could have consequences rippling beyond the UK and affect the global supply of medical devices and diagnostics.

To stay on top of the changing requirements and implementation expectations, see the complete listing of official guidance documents on MDR and IVDR here.

What’s Coming in October?

October will bring together a number of timely issues facing regulatory professionals today, including the advantages of using periodic safety update reports, practical solutions to pharmaceutical labeling challenges, the continued importance of consumer access to Chinese medicine, global gene therapy regulations and the regulatory requirements for ‘herbasimilars.’ Look for these and other topics throughout October.
 
Regulatory Focus Deadline for November Extended

Regulatory Focus is looking for subject matter experts to write articles for November featuring global regulatory implications of big data and digital health and the deadline has been extended to 31 October.
 
Big Data
 
Individual article topics could include:
  • What is big data, how can it be used, who is using it and what does it mean for regulatory professionals?
  • How will a regulatory professionals role and responsibilities change? SOPs?
  • Are regulatory requirements changing?
  • How will the utilization of big data impact the regulatory industry?
  • How is FDA using big data to proactively monitor the safety of medical products after they have reached the market complementing the agency’s existing Adverse Event Reporting System.
  • Global implementation strategies for obtaining/using/securing electronic healthcare data.
  • Case studies on how electronic healthcare data is being incorporated into a company’s global regulatory strategy
  • How is the pharmaceutical industry going to leverage big data in the coming years and how will it be implemented into its regulatory strategy?
  • Compare or describe EMA and EDA approaches to the use and interpretations of big data
  • How do regulatory agencies in Asia view big data? South America? Other regions?
  • How to establish a protocol review committee for observational research using big data?
Digital Health
 
Individual article topics could include:
  • Software as a medical device
  • Cybersecurity
  • Medical device interoperability
  • Regional similarities and differences in regulation of digital health products
  • Regulation of specific types of digital health products such as wearables, digital surgery devices, and mobile medical apps for example
  • Clinical quality in digital health
  • New and emerging regulatory models for digital health
  • The convergence of digital health with existing product categories and how regulation might support or hinder this convergence
  • Case studies on the regulatory approvals of a digital health product, including details on the regulatory approach taken, hurdles or barriers overcome
If you are interested in submitting an article for November or have a topic recommendation, email Gloria Hall at ghall@raps.org.

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