July 9, 2020

[FREE WEBINAR] How to Assess Your CER for MDR Readiness, Part 2: Clinical Data Sources, Equivalence, and Risk/Benefit Analysis

Get a copy of the slides from this webinar or click to watch the recording.

In this second part of our 2-part webinar series, Criterion Edge will continue to present strategies for assessing key components of your CER for possible misalignment with key EU MDR requirements. Presented from the perspective of seasoned regulatory writers with deep experience authoring MedDev rev. 4 and MDR-compliant CERs, this practical presentation will help you assess your document through the critical lens of a writer and identify possible gaps for mitigation before prior to submission to regulatory authorities. In this series, we will examine the Clinical Data Sources, Equivalence, and Risk/Benefit Analysis Profile sections of the CER. 

In the first webinar of this series, we discussed the State of the Art, Safety & Performance Criteria, Equivalence, and Systematic Literature Review.
Click here to get the slides and watch the recording for part 1.

Key Takeaways:
• Understand the key components of a clinical evaluation report (1-min review of last webinar, clinical evidence, SLR, risk benefit, conclusion – have you ensured that your conclusion reflects conclusions from other sections/data?) 
• Determine how to evaluate your CER for key requirements of the MDR 

Who should watch this webinar?
Those Regulatory, Quality and Clinical leaders and regulatory writers who are tasked with the development, writing, review or approval of Clinical Evaluation Reports for EU MDR submission, or anyone interested in learning more about MDR requirements for CERs.

Sign up for future webinars here.


If you enjoyed this webinar and would like a free consultation, please contact us here.

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July 6, 2020

IVDR 2017/746 Implements Risk-Based Classification of IVDs that Focuses on Intended Use

Author: Suzanne Broussard

The new In Vitro Diagnostic Regulation (IVDR) 2017/746 brings significant changes to the regulation of In Vitro Diagnostic (IVD) devices in the European Union (EU). One of the biggest changes is the use of risk-based classes for IVDs that require significant clinical support and regulatory oversight, and the deadlines for compliance are looming as the IVDR transition period ends on May 25, 2022.   

The switch to IVDR will have an enormous impact on the requirements to obtain a CE Marking. Under current European Union regulations, only 10% to 20% of IVDs sold under the In Vitro Diagnostic Directive (IVDD) require Notified Body (NB) assessment. This flips with under IVDRs new risk-based classification system, and an estimated 70% to 80% of IVDs will requiring Notified Body (NB) review. 

The new IVDR 2017/746 classification of IVDs is based on an internationally recognized risk-based classification system that places IVD devices in four classes (A-D) based on the intended use of the device, which ultimately determines the risk to both the patient and the general population. Class designation is determined using 10 implementing rules and 7 classification rules.  

Classification: Risk-Based Class Designation is Determined Using 7 Classification Rules

IVDR classes are based on globally accepted criteria developed by the Global Harmonization Task Force (GHTF) in February 2011 (GHTF evolved into what is now known as the International Medical Device Regulators Forum [IMDRF]). The risk classes are A through D; class A devices have the least risk, and class D devices have the most risk. This risk-based classification is replacing the list-based classification of the IVDD 98/78/EC and will result in the vast majority of IVDs being up-classified. 

Let’s look directly at the IVDR regulation’s seven Classification Rules that are outlined in Annex VIII of IVDR 2017/746. These rules first define each class and are explained in each class below. The rules start identifying devices that have the most risk to both the patient and population (Class D) and then continue with criteria for IVDs that pose less risk. Correctly determining the device classification is critical as the class dictates the level of clinical support and documentation required and the need for NB review. It is important to understand that the classification is based on the devices intended purpose, and thus the risk to the patient and population. 

Class D devices have a high risk to the patient and a high risk to public health, and therefore must meet the highest level of conformity. Rule 1. 

Class D devices are governed by Rule 1 under Classification Rule 2.1. They include devices that detect the presence of, or exposure to, transmissible agents, life-threatening transmissible agents, and infectious disease with a high risk of propagation.  

Class C devices have a high risk to the patient and/or medium risk to public health, and are defined in Rules 2, 3, 4.  

The IVD devices in class C according to Rule 2 are intended to be used for blood grouping or tissue typing, blood components, cells, tissues or organs intended for transfusion or transplantation, with some exceptions explicitly stated.  

Devices in class C according to Rule 3 are intended to be used for infectious agents without a high risk of propagation, pre-natal screening, companion diagnostics, monitoring levels of medicinal products, detecting congenital disorders in embryos, foetus, or new-born babies; and genetic testing.  

Rule 4 further defines class C devices as those that are intended for self-testing “except for devices for the detection of pregnancy for fertility testing and for determining cholesterol level, and devices for the detection of glucose, erythrocytes, leucocytes and bacteria in urine, which are classified as class B. 

Class B devices have moderate individual patient risk and/or low public health risk. Class B devices are defined under Rule 4 and 7; class B is also the default class for devices that do not fall within the scope of any stated rules (Rule 6).  

Class B devices are less risky than class C devices and include the self-testing devices that are exempt from class C in Rule 4 (see class C above), such as those used to detect glucose. Rule 7 states that “Devices which are controls without a quantitative or qualitative assigned value are classified as class B.” 

Class A devices have a low risk to the patient and low public health risk

Under Classification Rules 2.5 Rule 5, the following devices are classified as Class A: 

  • products for general laboratory use, accessories which possess no critical characteristics, buffer solutions, washing solutions, and general culture media and histological stains, intended by the manufacturer to make them suitable for in vitro diagnostic procedures relating to a specific examination;  
  • instruments intended by the manufacturer specifically to be used for in vitro diagnostic procedures;  
  • specimen receptacles. 

Under the new classification rules, it is estimated that the vast majority of IVDs will be class B or class C. When classifying an IVD, it is important to first look at the implementing rules, 1.1 to 1.10 of the Classification Rules. As you can see below, the implementing rules provide manufacturers with additional information as to which class the device is categorized, especially in regard to combination products and multiple-use devices.

Implementing Rules (Annex VIII) 

1.1 Application of the classification rules shall be governed by the intended purpose of the devices.  

1.2 If the device in question is intended to be used in combination with another device, the classification rules shall apply separately to each of the devices. 

1.3 Accessories for an in vitro diagnostic medical device shall be classified in their own right separately from the device with which they are used.  

1.4 Software, which drives a device or influences the use of a device, shall fall within the same class as the device. If the software is independent of any other device, it shall be classified in its own right. 

1.5 Calibrators intended to be used with a device shall be classified in the same class as the device.  

1.6 Control materials with quantitative or qualitative assigned values intended for one specific analyte or multiple analytes shall be classified in the same class as the device.  

1.7 The manufacturer shall take into consideration all classification and implementation rules in order to establish the proper classification of the device.  

1.8 Where a manufacturer states multiple intended purposes for a device, and as a result the device falls into more than one class, it shall be classified in the higher class. 

1.9 If several classification rules apply to the same device, the rule resulting in the higher classification shall apply. 

1.10 Each of the classification rules shall apply to first line assays, confirmatory assays, and supplemental assays.  

It is projected that the vast majority of IVDs will fall into class B or class C. Many devices currently on the market will be reclassified into a higher risk based on the IVDR classification and, thus, require significant investment from the manufacturer to remain regulatory compliant. All devices that fall in Class B, C, and D have conformity assessment procedures that require NB assessment, as do some class A devices that require sterilization.  

Our next blog will cover Analytical and Clinical Technical Documentation for IVDR 2017/746 Compliance and Software as Part of IVDR. Also, check out to the first post in this series.  


Please reach out to us with any questions or to find out how we can help your organization transition to compliance with IVDR 2017/746.

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June 30, 2020

Key Changes in the Regulatory Requirements for In Vitro Diagnostic Devices Marketed in the European Union Under IVDR 2017/746

Author: Suzanne Broussard

In vitro diagnostic (IVD) medical devices in the European Union are being held to a higher standard of scrutiny with the introduction of In Vitro Diagnostic Regulation (IVDR) 2017/746 by the European Commission (EC). 

Overview of In Vitro Diagnostic Regulation 2017/746  

The implementation of IVDR dramatically changes the regulatory landscape for IVD medical devices. Some of the biggest changes include an expanded definition of IVDs, a new classification of IVDs, the requirement of Unique Device Identification (UDI) on each device, an expansion of the Quality Management System, and the increased need for Notified Body (NB) review.  

The transition into IVDR is already underway. IVDs marketed in the EU will continue to require a CE Marking certificate to verify that the device meets all the regulatory requirements. Failure to meet the IVDR deadlines could be very costly to manufacturers that would either lose their CE Marking or fail to obtain one. The timeline below outlines the deadlines for manufacturers to become compliant with IVDR 2017/746. 

IVDR Timeline 

The IVDR is being implemented over a 5-year transition period in which it will fully replace the current In Vitro Diagnostic Directive (IVDD) 98/78/EC (Figure 1). IVDR 2017/746 was published May 5th, 2017, in the Official Journal of the European Union, and officially went in to affect May 25th, 2017; that means we are almost halfway through the transition period. During the transitional provisions, manufacturers can meet either IVDD or IVDR requirements. However, starting May 26, 2022, all new IVDs must go through IVDR. Some devices that lawfully obtained IVDD certificates have another 2-year grace period and may continue to be made available until May 27, 2025 (depending on serval factors). 

Article 110 Transitional provisions state that “Certificates issued by notified bodies in accordance with Directive 98/79/ED[EC] prior to 25 May 2017 shall become void by 27 May 2024.” IVDs that obtained certificates in accordance with IVDD prior to May 25, 2017 are valid until the end of the period indicated on the certificate, with some exceptions. Certificates issued under Directive 98/79/EC Annex VI become void at the latest May 27, 2024. If a device is lawfully placed on the market under IVDD prior to May 26, 2022 and placed on the market from May 26, 2022 by a certificate (refer to paragraph 2 and 4), the IVD can be on the market or put into service until May 27, 2025.  

See IVDR Article 110 and the IVDR Corrigendum number 8 for specific details. 

Starting May 26, 2024 IVDR will be full application, and all IVDs must be fully compliant.  

Figure 1. IVDR Timeline 

A screenshot of a cell phone Description automatically generated

It may seem that there is plenty of time to obtain IVDR compliance, but there are many hurdles to obtaining CE Marking under this new regulation. Also consider that there are major changes in almost every aspect regulation for medical devices in the EU, including MDR, MedDev2.7/1 rev.4, and CERs.   

Scope of IVDR 

The scope of IVDR is massive, and it impacts all aspects of in vitro diagnostic device manufacturing.  

  • The definition of an IVD is expanded to included software and companion diagnostics.  
  • This requires IVDs to use a new device classification system that will place 70%-80% of IVDs in a new category, and, thus, requiring significant work to obtain or maintain market approval.  
  • There is no grandfathering of any device. Even those currently on the market, must conform to the new IVDR standards. 

If you are marketing or intend to market any type of In Vitro Diagnostic Medical Device in the European Union, it is time to act. With the need for NBs substantially increasing, it is important to start the process of performing a Gap analysis and finding a NB.  

Let’s start by first looking at the newly expanded definition of IVDs under IVDR 2017/746.  

If you are marketing or intend to market any type of In Vitro Diagnostic Medical Device in the European Union, it is time to act. With the need for NBs substantially increasing, it is important to start the process of performing a Gap analysis and finding a NB.  

Let’s start by first looking at the newly expanded definition of IVDs under IVDR 2017/746.  

Definition of In Vitro Diagnostic Devices 

Section 1, Article 2 of IVDR 2017/746 expands the definition of IVDs. The addition of software and companion diagnostics to the definition of in vitro diagnostic devices significantly expands the definition of IVDs. Software is a medical device according to the definition of IVD if that is its intended purpose; thus, software as part of an instrument, software as a medical device, and apps are included in the definition of IVDs and fall under IVDR regulation. This includes genetic testing, companion diagnostics, as well as stand-alone software. 

The specific definition of In Vitro Diagnostic devices from IVDR 2017/746 is below. 

(2) ‘in vitro diagnostic medical device’ means any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, piece of equipment, software or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information on one or more of the following: 

(a) concerning a physiological or pathological process or state; 

(b) concerning congenital physical or mental impairments; 

(c) concerning the predisposition to a medical condition or a disease; 

(d) to determine the safety and compatibility with potential recipients; 

(e) to predict treatment response or reactions; 

(f) to define or monitoring therapeutic measures. 

Specimen receptacles shall also be deemed to be in vitro diagnostic medical devices; 

Section 1, Article 1, 3. Defines what the IVDR does not apply to: 

  1. products for general laboratory use or research-use only products, unless such products, in view of their characteristics, are specifically intended by their manufacturer to be used for in vitro diagnostic examinations; 
  1. invasive sampling products or products which are directly applied to the human body for the purpose of obtaining a specimen; 
  1. internationally certified reference materials; 
  1. materials used for external quality assessment schemes.  

The next blogs in this series will cover the new Classification Rules.  


Please reach out to us with any questions or to find out how we can help your organization transition to compliance with IVDR 2017/746.

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June 23, 2020

The Deadline for Compliance with MDR 2017/745 is Extended to 26 May 2021: Changing and Challenging Dynamics

Author: Suzanne Broussard

The global COVID-19 pandemic prompted the 1-year extension of the Medical Device Regulation (MDR) 2017-745 date of application. The delay is creating a changing and challenging dynamic landscape for device manufacturers and notified bodies (NBs). 

As the seriousness of the COVID-19 pandemic emerged in March, the European Commission recommended a 1-year extension to the MDR date of applicability, the Parliament and Council then acted quickly with an almost unanimous decision supporting the delay, and the extension was ultimately accepted by the member states and published in the Official Journal on 23 April 2020. 

The ongoing pandemic has created a high demand for resources such as surgical masks, medical gloves, and other medical and personnel protective equipment — keep these supplies flowing is a top priority to protect both patients and healthcare workers. The delay of the MDR date of applicability was implemented to ensure that hospitals and healthcare facilities have a continued supply of devices during the critical times of the pandemic.  

It is important moving forward to understand that the delay was not implemented to provide manufacturers with more time to become compliant with MDR, and the European Commission expects that manufactures are continuing to work to comply with the newest regulation. However, the delay presents both opportunities and challenges for manufacturers. 

Opportunities 

Of course, the biggest benefit of the delay is time. Time that is in short supply for manufacturers and NB dealing with the ongoing changes to device regulations. The extra time may most benefit manufacturers of class I devices that were short on time to take advantage of the grace period provided under the second corrigendum of MDR 2017/45.  Manufacturers in the following positions have the most to gain by the 1-year delay. 

  • Class I Devices with Significant Changes: The Second Corrigendum of MDR 2017/745 provides a grace period for some self-declared class I devices under MDD. The grace period essentially means that qualifying class I devices do not need to be certified to the new MDR regulation but instead can utilize the MDD Declaration of Conformity until the 25th of May 2024. However, the class I device cannot have significant changes. The additional time may allow manufacturers of class I devices that are likely to be up classified under MDR and have not already done so the time to make the necessary revisions and complete an MDD CE certification. 
  • Renewal of MDD Certification: Device manufactures that needed a little more time to renew their Medical Device Directive (MDD) or Active Implantable Medical Devices Directive 90/385/EEC (AIMDD) CE-certification now have some breathing room. The impact on manufacturers that may have just missed the original deadline for the MDR date of application is immense since devices with a current certification under MDD are allowed to utilize the transition period covered in MDR 2017/745 giving 3 more years to become fully complaint in 26 May 2024. 
  • Compliance with Post-Market Surveillance, Market Surveillance, Vigilance, and Registration of Economic Operators:  This is an important area for manufacturers since they must still set-up and maintain a number of systems for the application of MDR. Manufacturers need to develop and implement quality management systems and procedures for risk management, clinical evaluation, and post-marketing surveillance (PMS) / post-market clinical-follow-up (PMCF). These processes take time to develop and improve. Likewise, logistic issues like Economic Operator requirements and contracts can be evaluated.   
  • Notified Bodies: The European Commission and EU Member States will have an additional year to accredit NBs under the MDR. The number of NBs is still far fewer than the original projections, and these NBs are overextended working with manufacturers that are scrambling under these tight deadlines to obtain an early MDD to take advantage of MDR’s transitional provisions.  

The delay is also creating several challenges for both manufacturers and NBs. 

Challenges 

Medtech Insight hosted an MDR discussion panel consisting of 3 outspoken and renowned experts on the regulations of medical devices in the European Union: Bassil Akra  of  QUNIQUE consultancy (formally of TÜV-SÜD notified body), Gert Bos of Qserve consultancy, and Erik Vollebregt of Axon Lawyers.1 

The take home message from this highly respected panel was simple. 

A year is not an extra year. 

Several important considerations were raised in the panel discussion that device manufacturers should take into consideration. 

  • NBs are working very hard to get class I devices that are eligible into the grace period provided by the Second Compendium published as recently as 25 November 2019. In order to take advantage of the grace period, the current MDD certification has to be renewed by the date of MDR application (now the extended 26 May 2021 date). This is a real hurdle because many class I device manufacturers have not used NBs in the past, and therefore many of these manufacturers really need the delay to adequately prepare 
  • The large medical device manufacturers are accustomed to working in this regulatory space, but many of the smaller distributors and third-party logistics (3PL) companies still have a fair amount of confusion and it takes time for all the news to trickle through the pipeline. 
  • Only a handful of NBs (2) are currently focused on new MDRs, most of the 14 NBs are focused on renewals and may not have enough time or resources to transition from MDD to MDRs. 
  • There has been a flurry of guidance documents published in May, giving manufacturers little time to react to the interpretations. NBs and manufacturers are hoping for a more relaxed interpretation of the guidance documents, but there is no guarantee the member states will have consistent implementation. 

The panelists agree there is much to do moving forward.   

The additional challenges of social distancing and the general global lockdown brought on by the pandemic will impact the ability of NBs and manufacturers moving forward. A recent ruling allowing NBs to conduct virtual audits for MDD renewal was critical. However, delays will make the new extension seem like much less than a year. 

1. EU MDR Panel Discussion: Why An Extra Year Is Not Really A Delay For The MDR – How To Survive Changing And Confusing Times. Medtech Insight https://medtech.pharmaintelligence.informa.com/MT142211/EU-MDR-Panel-Discus 


Reach out to Criterion Edge for support getting your technical documents ready for MDD renewal or the MDD to MDR transition. We have expert medical writers to support your organizations in developing the necessary documents to ensure a smooth transition and meet these fast-moving deadlines. Get a free consultation today. 

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