MedDev Day

This presentation will look to provide the early experience and some insights (from a notified body point of view) on the clinical evaluation assessments carried out under the new medical device regulations.

• How have NBs conducted assessments under the MDR (compared to MDD).
• What difficulties have been encountered in the assessment of manufacturer’s technical documentation. There will be some emphasis on the review of the CER and PMCF.

The clinical evaluation process allows a manufacturer of a medical device to evaluate if there is sufficient clinical evidence to declare compliance with safety, performance and benefit / risk ratio essential requirements. Within this process the claims made by the manufacturer are a fundamental input that should be taken into consideration at a very early stage, namely during planning and scoping of the clinical evaluation. Indeed, the claims made embody the foundations for the entire process.
The aim of this session is not only to discuss the controversy under the definition of “claim”, but also to provide practical considerations and best practices on how to analyze and find correct sources to substantiate claims. In particular, we will discuss:

• The different types of claims
• The importance of claims in the clinical evaluation process
• Sources for substantiation of claims: clinical data and more
• The re-evaluation of claims in the post market phase
• Considerations for legacy medical devices transitioning to MDR

Putting a medical device on the market is widely seen as a linear process with two separate stages, that of pre and post-market. These tend to be independently managed, and although they rely one another they are unlikely to know each other’s regulatory requirements or the ways that they could collaborate to help a product to thrive on the market. The observational data of real-world evidence (RWE) has not traditionally been a focus for pre-market clinical teams. Now however, the EU’s medical device regulation (MDR) and in vitro diagnostic medical device regulation (IVDR) radically reinforces the regulatory requirements for clinical trials for pre and post-marketing, citing these as vital to ensuring the safety and performance of a product on the market.

New technology now enables us to review, analyse and utilise clinical data from real-world applications for regulatory purposes, health tech assessments and more. We can design clinical trials with the RWE manuscript in mind and in turn use RWE to influence new clinical trials that can support the lifecycle of a product on the market.

Whilst this talk will define the framework of these new regulatory requirements, it will also highlight the fact that RWE can now be used and shared to support the regulatory requirements for a device.

This presentation will focus on the new changes introduced by the ISO 14155:2020 update, and the relation these have with the new requirements of the MDR 2017/745 Section VI (articles 61-82 + Annex XV). The aim will be to provide a practical approach to clinical investigation management, addressing the need of all stakeholders involved.

Among the changes introduced by the last edition of ISO 14155:2020 we note:

• the inclusion of a summary section of GCP principles
• reference to registration of clinical investigation in a publicly accessible database
• inclusion of clinical quality management
• inclusion of risk-based monitoring
• inclusion of statistical considerations
• inclusion of guidance for ethics committees
• reinforcement of risk management throughout the process of a clinical investigation (from planning to results)
• clarification of applicability of the requirements of this ISO to the different clinical development stages
• inclusion of guidance on clinical investigation audits.

Furthermore, practical aspects of clinical investigation set up will be discussed, as well as specific considerations of risk management of clinical investigations, the set-up of specific plans for clinical investigation managements as well as the critical aspects checked during audits and inspections.

The medical device regulation was published in May 2017 with a transition period of 3 years. Due to COVID19 Pandemic, the date of application of the regulation was postponed to May 2021 instead of May 2020. This delay gave manufacturers and other related stakeholders additional time to prepare their system for the MDR and to close ongoing projects under the directives MDD and AIMDD. According to the MDR transitional provisions listed in Article 120, any medical device manufacturer planning to place devices on the market from 26 of May 2021 must comply with the post-market surveillance of the EU MDR. This obligation applies also to directive devices making use of the grace period.

During this presentation, we will present the expectations of notified bodies and when relevant surveillance authorities and share some helpful guidance towards compliance with the new requirements.

Attendees of this session will learn about feasible methodologies to comply with the active post-market surveillance requirements throughout the entire lifetime of the device.

The EU Medical Device Regulations reinforce the rules on clinical evidence and post market surveillance for medical devices. Manufacturers are required to perform Post Market Clinical Follow-up (PMCF) as a continuous process that updates the clinical evaluations of their devices with new clinical data. A wide range of PMCF activities can be used to collect this data including clinical investigations, registries, surveys and literature reviews. The PMCF methods vary in the type and quality of clinical evidence that can be collected.

In this presentation we will review the PMCF requirements and, based on recent experience with PMCF planning, data collection and notified body acceptance, we will give insights in how to identify and address clinical data gaps using appropriate PMCF methods. Lastly, the role of PMCF in life cycle management will be discussed.

The harmonized terminology and coding system for adverse event reporting for medical devices established by the IMDRF enables the use of a standardized language across quality management system processes.

How have device manufacturers integrated these codes into existing QMS processes? And how can companies ensure optimal alignment across all teams using the coding system?

This case study will showcase best practices and lessons learned from the implementation of IMDRF coding (Annexes A, E, and F) in the clinical evaluation process and how these processes were aligned cross-functionally with complaint reporting, post-market surveillance, and risk management teams.

During this interview we will discuss the interactions between post market surveillance, clinical evaluation and risk management regarding clinical data.

The Medical Device Regulation intensifies the focus on clinical data that is necessary to fulfill the general safety and performance requirements. Where the MDD spent 2 pages on the topic, the regulation has 60 pages on clinical evidence. The processes described in these sections interact with each other. The clinical evaluation process receives information form the risk management process but also gives input into the risk management process. When the product is launched, the PMS activities start in parallel and collects reactively and proactively clinical data. This output affects the clinical evaluation and therefore the risk management processes as well.

This is also a circle with different interactions: the clinical evaluation provides input into the PMS plan. It is obvious to conclude that the clinical evaluation interactions with the PMS as well as the risk management processes.

These 3 processes form the base for the assurance of the wellbeing of the user/patient. It also is the base for several documents related to the device such as the IFU and the summary of safety and performance which are shared with the public.

Under the IVDR, the system of how products are placed on the market has been completely revolutionized. Under the old regime of the IVD directive, there was no direct division of products by class. Besides the products that required a Notified Body (Annex II A/B + self-tests) to CE mark products, all other tests were previously grouped under ” diverse”.

This has changed completely: Under the IVDR, there are 4 risk classes (A-D) grouped according to the risk of the disease/condition and consequent misdiagnosis to the patient. 7 rules and 10 implementing regulations specify how the respective products are classified.

In addition, the relevant body for the implementation of the IVDR (MDCG) has issued a living guidance document on classification.

How have manufacturers implemented the IVDR requirements into their Quality Management System?

This presentation will give an overview of the regulatory requirements followed by examples to demonstrate how a manufacturer has implemented the requirements in its QMS:

• The individual elements of the technical documentation, where they come from, what they must contain will be explained and demonstrated with examples.
• A deep dive into the challenges for a manufacturer to fulfil those requirements and adjust existing processes and structures. Differences based on risk classification and the resulting consequences.

The lecture concludes with a question and answer session.

IVDR implementation during the uncertain time of Corona Pandemic remains challenging. Almost all organizations were forced to adjust/delay the IVDR program implementation. The whole process of Implementation became challenging due to compulsory home office rules, focus shift to Corona Tests, lack of notified bodies, Reference labs, and Audits (Internal and external).

During this session, we will present a case study on the IVDR implementation during COVID-19 pandemic.

The presentation will focus on:

• An overview of the PMS requirements under the IVDR and their impact on Technical Documentation
• Current status of guidance on PMS for IVDs: what guidance documents are already available and which are still expected after the IVDR Date of Application
• Notified Body perspective

Most medical device companies still work with Word, Excel and PDF files which leads to inefficiency when it comes to creation and maintenance of the technical documentation. This presentation summarizes current challenges with the MDR and in particular for clinical evaluation, PMCF and PMS processes.

Key problem is the reuse of single information across different documents, which results in copy and paste of text elements or references between different documents. Since documents are changed quite often, inconsistencies are inevitable. On the other hand, Notified Bodies often ask for “stand alone” documents including the complete relevant content. In summary: Manufacturers and Notified Bodies have different perspectives on the technical documentation, often resulting in unnecessary discussions and findings that extend the regulatory approval procedure.

Software tools provide a solution for that dilemma, but the implementation is often associated with lots of time, money, and the need for extensive internal resources. Advantages but also disadvantages of software tool implementations are explained and the potential of a unified data model for medical devices highlighted. At the end, an outlook is given on current trends and how creation, maintenance and review of the technical documentation will change in the next 5 years – for medical device manufacturers but also for Notified Bodies.

Overseeing the implementation of standards and regulations for medical devices, while allowing a business unit to remain in compliance with those regulations is one of the biggest challenges of the MedTech industry under the MDR.

The process requires regulatory managers to be knowledgeable in the nature and application of regulations. Still when facing far away geographical areas, such as China, they may find it difficult to avoid any type of censure from government agencies or even from colleagues working abroad.

Through this interactive talk, we will address, among others:

• What are the importance of Regulatory Management.
• What are the key terms and regulatory systems for the Medtech industry.
• Tips to get product registration approval quicker in Asia.
• Cultural communication barriers in international business.

Overseeing the implementation of standards and regulations for medical devices, while allowing a business unit to remain in compliance with those regulations is one of the biggest challenges of the MedTech industry under the MDR.

The process requires regulatory managers to be knowledgeable in the nature and application of regulations. Still when facing far away geographical areas, such as China, they may find it difficult to avoid any type of censure from government agencies or even from colleagues working abroad.

Through this interactive talk, we will address, among others:

• What are the importance of Regulatory Management.
• What are the key terms and regulatory systems for the Medtech industry.
• Tips to get product registration approval quicker in Asia.
• Cultural communication barriers in international business.

Regulatory management can be defined as the process of dealing with regulatory requirements pertinent to a market. Viewed in a global context this process requires capabilities that a company must possess to operate in a global regulatory environment that is increasingly complex and in a state of continuous change. Which makes regulatory management one of the most important parts of medical device company’s corporate management.

This presentation will focus on interrelations of corporate management, company’s regulatory function and regulatory environment. It will cover the following topics (including cases and examples):

• The place of regulatory management in a medical device company: product lifecycle and regulatory cycle, relationships with other areas of management, global and corporate regulatory perspectives
• Regulatory management components: leadership, resources, processes, expertise, strategy
• How to build the global regulatory management system based on “horizontal” and “vertical” standards and implement it at the regional level
• Global and regional regulatory management: the similarities and differences.

For hardware manufacturing companies there are some challenges to overcome when entering the digital business of software as medical device (SaMD). Different requirements in terms of policies, regulatory and interoperability need to be fulfilled. Including the focus on patient centricity adds another complexity on the ambition to valuably deliver end to end (E2E) solutions.

In a society that is becoming increasingly digital, the use of digital health solutions in healthcare is often less common or available than we might expect. As national authorities search for new and better ways to assess innovative technologies, overall coordination is often lacking and can lead to a heavily fragmented European market. Inconsistencies in market access requirements are increasing the time and costs of bringing digital health solutions to market.

Based upon several national case studies we will discuss opportunites and challenges, and present recommendations to make digital health solutions more accessible to European citizens and patients.

During this session we will take a deep-dive into the requirements around Cybersecurity for medical devices and touch on the definition of requirements, testing and risk management.
Among others, we will address:

• What are the sources for cybersecurity requirements for SaMD (MDR 2017/745, FDA, other)
• Which are the requirements coming forth from Medical Device Standards (e.g. ISO 27001, IEC 82304, other)
• What do you need to consider with regards to Security Risk Management for SaMD?
• Are there specific risks for AI SaMD?
• How do you validate Cybersecurity for medical devices?
• How does your cybersecurity approach link to the Clinical Evaluation Report (CER)?

Artificial intelligence (AI)-driven devices are constantly developed, yet are forced through conventional clinical evaluation criteria globally. The AI technology in question demands AI-centred validation. Key ideas such as

• interpretability and explainability of outcome,
• device accuracy performance studies vs agreement studies,
• arriving at a suitable sample size to prove the clinical validity,
• developing ground truth or gold standard methods as the reference points, and
• validating devices at their intended application

are some of the existing questions clinical evaluators must reconsider when validating an AI-driven device.

Unfortunately, as there is a general lack of industry-wide guidance for clinical evaluation of AI-driven devices, how can stakeholders diligently work to ensure a high-quality AI application is administered in clinical settings? Until a recognised industry standard is established for AI medical / IVD devices, a large portion of clinical evaluation studies ought to be highly customised to the AI technology in question.