The In Vitro Diagnostic Regulation (IVDR 2017/746), provides a harmonised regulatory framework to ensure the safety and performance of devices in the European Union (EU).
In contrast with current directives, the new IVDR classification system requires most IVD devices to be subject to verification and certification by notified bodies (NBs). This new classification system presents an enormous change, as broadening scope of the rules means that approximately 80 to 90 percent of all IVDs will now require conformity assessment by an NB, compared to only 10 to 20 percent of devices undergoing this process under the IVDD.
With dramatically increased workloads for NBs and reference laboratories, significant bottlenecks and delayed product reviews should be expected. This will be particularly relevant for IVDs classified as high-risk, because these devices will require a greater amount of attention and documentation. With the need to prove compliance to a NB prior to CE marking further complicating the IVDR transition process, an increased burden on IVD manufacturers may result in a higher cost of regulatory compliance if they do not have a thoughtful strategy in place. Here we discuss how to develop a regulatory and clinical evidence outcomes strategy for high risk IVDs.
Understanding the new risk-based classification system
Under IVDR, IVDs will fall into one of four classifications from class A (low risk) to class D (high risk). These classifications are defined by the intended purpose of the device, which must be clearly specified by the manufacturer on the device label, the performance evaluation or in promotional or sales materials. Failure to clearly communicate this information, or ambiguous claims around the uses of the device, may lead to higher classification. This is important to note because different device classifications under the IVDR have different documentation requirements.
To help manufacturers better understand the nuances of this updated classification system, a new guidance was published in November 2020 providing information on how to classify an IVD prior to placing it on the market. Careful review of guidances in conjunction with IVDR is critical because if an NB does not agree with the manufacturers classification, a dispute process may be initiated. Important information that is often omitted include design specifications, final quality control inspections, legacy information and promotional materials. If feedback is not addressed within three rounds of review, the device application can be rejected and will be reported to EUDAMED. With these challenges in mind, classification of devices should be one of the first steps in each manufacturer's transition strategy.
Developing a regulatory and clinical evidence outcomes strategy
In addition to understanding the new classification requirements, manufacturers can prepare for regulatory submission by performing a portfolio assessment and gap analysis to address new requirements for each device and determine how to best prioritise resources moving forward. This portfolio assessment should include review of profitability, marketability and patient need for each product. Additionally, a gap analysis of current documentation can help manufacturers determine additional needs.
Once these processes are complete, technical documentation should be created or updated in preparation for regulatory submission. Under IVDR, it is useful to note that although every product will require technical documentation, it will not require its own technical file. Manufacturers of high-risk products can save time and resources by combining multiple products with the same classification, analyte or dedicated assay systems. For example, an assay, calibrator and control may have different SKUs, but if they are dedicated they can be combined into one technical file rather than three technical files.
In addition to technical documentation, high-risk devices will require a greater amount of clinical evidence than other IVD classifications. Due to the up-classification of many devices, manufacturers may be required to perform clinical testing on devices that previously did not require it. To aid in the process of collecting clinical evidence, manufacturers should develop a performance evaluation plan (PeP), which specifies the characteristics and the performance of the device, as well as outlines the processes and criteria to generate the clinical evidence. In addition to the PeP, a performance evaluation report (PER) should be assembled, which should be inclusive of the clinical evidence summary and the following three attachment reports:
- Analytical Performance Report, which presents evidence that the IVD performs as designed
- Clinical Performance Report, which presents evidence that it performs as designed in a clinical setting
- Scientific Validity Report, which focuses on the analyte, or target, and its clinical uses
This report will need to be continually updated. IVD manufacturers that have already begun these assessments will be well-prepared for the transition.
Finally, once technical documentation and clinical evidence are gathered, all materials should be submitted directly to a NB. A direct working relationship can ensure improved efficiency in gaining approval and ultimately maintaining market share under IVDR.
Conclusion
Current trends are proving that IVD developers must move faster to comply with IVDR by the deadline. Manufacturers who have not begun preparations will need to adopt a strategy to address gaps in meeting the new regulation. To help navigate the complexity of this transition, it can be useful to involve top management in compliance efforts, as well as seek external expertise. To learn more about how to develop an effective transition strategy, read our whitepaper: The IVDR journey.
In this section
-
Digital Disruption
- AI and clinical trials
-
Clinical trial data anonymisation and data sharing
-
Clinical Trial Tokenisation
-
Closing the evidence gap: The value of digital health technologies in supporting drug reimbursement decisions
-
Digital disruption in biopharma
-
Disruptive Innovation
- Remote Patient Monitoring
-
Personalising Digital Health
- Real World Data
-
The triad of trust: Navigating real-world healthcare data integration
-
Patient Centricity
-
Agile Clinical Monitoring
-
Capturing the voice of the patient in clinical trials
-
Charting the Managed Access Program Landscape
-
Developing Nurse-Centric Medical Communications
- Diversity and inclusion in clinical trials
-
Exploring the patient perspective from different angles
-
Patient safety and pharmacovigilance
-
A guide to safety data migrations
-
Taking safety reporting to the next level with automation
-
Outsourced Pharmacovigilance Affiliate Solution
-
The evolution of the Pharmacovigilance System Master File: Benefits, challenges, and opportunities
-
Sponsor and CRO pharmacovigilance and safety alliances
-
Understanding the Periodic Benefit-Risk Evaluation Report
-
A guide to safety data migrations
-
Patient voice survey
-
Patient Voice Survey - Decentralised and Hybrid Trials
-
Reimagining Patient-Centricity with the Internet of Medical Things (IoMT)
-
Using longitudinal qualitative research to capture the patient voice
-
Agile Clinical Monitoring
-
Regulatory Intelligence
-
An innovative approach to rare disease clinical development
- EU Clinical Trials Regulation
-
Using innovative tools and lean writing processes to accelerate regulatory document writing
-
Current overview of data sharing within clinical trial transparency
-
Global Agency Meetings: A collaborative approach to drug development
-
Keeping the end in mind: key considerations for creating plain language summaries
-
Navigating orphan drug development from early phase to marketing authorisation
-
Procedural and regulatory know-how for China biotechs in the EU
-
RACE for Children Act
-
Early engagement and regulatory considerations for biotech
-
Regulatory Intelligence Newsletter
-
Requirements & strategy considerations within clinical trial transparency
-
Spotlight on regulatory reforms in China
-
Transfer of marketing authorisation
-
An innovative approach to rare disease clinical development
-
Therapeutics insights
- Endocrine and Metabolic Disorders
- Cardiovascular
- Cell and Gene Therapies
- Central Nervous System
-
Glycomics
- Infectious Diseases
- NASH
-
Oncology
- Paediatrics
-
Respiratory
-
Rare and orphan diseases
-
Advanced therapies for rare diseases
-
Cross-border enrollment of rare disease patients
-
Crossing the finish line: Why effective participation support strategy is critical to trial efficiency and success in rare diseases
-
Diversity, equity and inclusion in rare disease clinical trials
-
Identify and mitigate risks to rare disease clinical programmes
-
Leveraging historical data for use in rare disease trials
-
Natural history studies to improve drug development in rare diseases
-
Patient Centricity in Orphan Drug Development
-
The key to remarkable rare disease registries
-
Advanced therapies for rare diseases
-
Transforming Trials
-
Accelerating biotech innovation from discovery to commercialisation
-
Ensuring the validity of clinical outcomes assessment (COA) data: The value of rater training
-
Linguistic validation of Clinical Outcomes Assessments
-
Optimising biotech funding
- Adaptive clinical trials
-
Best practices to increase engagement with medical and scientific poster content
-
Decentralised clinical trials
-
Biopharma perspective: the promise of decentralised models and diversity in clinical trials
-
Decentralised and Hybrid clinical trials
-
Practical considerations in transitioning to hybrid or decentralised clinical trials
-
Navigating the regulatory labyrinth of technology in decentralised clinical trials
-
Biopharma perspective: the promise of decentralised models and diversity in clinical trials
-
eCOA implementation
- Flexible delivery models
-
Implications of COVID-19 on statistical design and analyses of clinical studies
-
Improving pharma R&D efficiency
-
Increasing Complexity and Declining ROI in Drug Development
-
Innovation in Clinical Trial Methodologies
- Partnership insights
-
Risk Based Quality Management
-
Transforming the R&D Model to Sustain Growth
-
Accelerating biotech innovation from discovery to commercialisation
-
Value Based Healthcare
-
Strategies for commercialising oncology treatments for young adults
-
US payers and PROs
-
Accelerated early clinical manufacturing
-
Cardiovascular Medical Devices
-
CMS Part D Price Negotiations: Is your drug on the list?
-
COVID-19 navigating global market access
-
Ensuring scientific rigor in external control arms
-
Evidence Synthesis: A solution to sparse evidence, heterogeneous studies, and disconnected networks
-
Global Outcomes Benchmarking
-
Health technology assessment
-
Perspectives from US payers
-
ICER’s impact on payer decision making
-
Making Sense of the Biosimilars Market
-
Medical communications in early phase product development
-
Navigating the Challenges and Opportunities of Value Based Healthcare
-
Payer Reliance on ICER and Perceptions on Value Based Pricing
-
Payers Perspectives on Digital Therapeutics
-
Precision Medicine
-
RWE Generation Cross Sectional Studies and Medical Chart Review
-
Survey results: How to engage healthcare decision-makers
-
The affordability hurdle for gene therapies
-
The Role of ICER as an HTA Organisation
-
Strategies for commercialising oncology treatments for young adults
-
Blog
-
Videos
-
Webinar Channel