Regulatory
Preparing for IVDR With the IVDR conferring stricter safety standards, European regulators have orchestrated a paradigm shift in the world of in vitro diagnostics (IVDs). The date of application is on 26th May 2022, supposedly giving an ample transition period. But manufacturers and other industry stakeholders don’t believe this is long enough given the significant changes. The stricter rules are designed to enhance safety and efficacy, and are especially tough for advanced molecular diagnostics and lab-on-chip assays used in the clinic to help identify a patient’s pathology. Further considerations for scrutiny for the first time are point-of-care products, such as self-administered pregnancy kits or at-home nutrigenetic tests. This change extends the concept of in vitro diagnostic devices to include tests of ‘indirect medical purpose’ and ‘prediction’ that are not covered by the current IVD Directive 98/79/EC (IVDD). The first of the fundamental changes is that IVDs will no longer be subject to the list-based system currently in the IVDD. Instead, they’ll be governed by the risk classes developed by the International Medical Device Regulators Forum (IMDRF), formerly known as the Global Harmonisation Task Force (GHTF). This approach uses a risk-based classification system, dividing the IVDs into risk classes from A (low risk) to D (high public and high patient risk), with seven classification rules. The rule-based system is devised to allow manufacturers themselves to identify the applicable risk class and to help determine the appropriate conformity assessment route available to achieve a CE mark. With the IVDR, the notified bodies are to perform conformity assessments on all but class A devices. This is a huge task, and has transformed the IVD regulatory landscape in terms of files to be reviewed and audits to be performed pre and post-market. The increased volume of work for the notified bodies stems from the widened scope of the IVD definition and the conformity assessment routes that are amended to fit the new classification logic. IVDs that do not fit any of the other classification rules fall into class B and have to be certified by a notified body. This is a major change compared with the IVDD, which allows such IVDs to be self-certified. As a consequence, 80% of all IVDs are to be certified by a notified body under the IVDR, compared with 20% currently certified under IVDD.
In terms of technical documentation, evidence of clinical performance studies is required to support the CE mark under the IVDR and, as a result, IVD manufacturers will need to produce significantly more clinical evidence. The IVDR contains rules for interventional clinical performance studies and other clinical performance studies that largely overlap with the clinical studies regime in the MDR, bringing it in
Medical Device Developments /
www.nsmedicaldevices.com
IVD statements
Prior to classification, an IVD should have statements prepared to address the following in Annex II, 1.1: (a) Determination if the product is an IVD and fits into the definition as per the IVDR. (b) A general description of the device, including its intended purpose and intended users.
(c) The intended purpose of the device, which may include information on: i. what is to be detected and/or measured
ii. its function, such as screening, monitoring, diagnosis or aid to diagnosis, prognosis, prediction or use as a companion diagnostic iii. the specific disorder, condition or risk factor of interest that it is intended to detect, define or differentiate
iv. whether it is automated or not v. whether it is qualitative, semi-quantitative or quantitative vi. the type of specimen(s) required vii. where applicable, the testing population viii. the intended user
ix. in addition, for companion diagnostics, the relevant target population and the associated medicinal product(s).
(d) the description of the principle of the assay method or the principles of operation of the instrument.
line with other global regulatory requirements. In preparation for compliance with IVDR, it is crucial for manufacturers of IVDs currently on the market and those entering the marketplace under the IVDR to plan the generation of additional clinical evidence well, and assess timely what’s required, how long it will take to generate it, and plan ahead for notified body slots for conformity assessment as part of the CE-marking process. The clinical performance evaluation includes not only the classic laboratory bench tests to support the clinical and analytical performance, but also scientific validity and, where applicable, using the appropriate statistical approach to substantiate claims.
At the present time, only a handful of the European Notified Bodies are designated to undertake IVD conformity assessment and, therefore, careful planning is important to avoid a bottle-neck situation closer to the IVDR date of application. In the present Covid-19 pandemic era, the IVD sector has seen increased activities for the production and regulation of CE-marked test kits under the IVDD. This has had a knock-on effect on the preparation for the IVDR.
Classification
Article 47 requires all IVDs to be classified into one of four classes. The classification determines the conformity assessment route for the device. While classification is primarily the concern of the manufacturer, Article 47 confirms that if a manufacturer and notified body cannot agree on the classification, the competent authority of the manufacturer is the body that makes the final determination. Before attempting to classify any device, it is recommended that manufacturers prepare
Gabriel Adusei, director, Triune Technologies (Consulting), founder of International Association of Consultants
Gabriel Adusei has over 30 years of experience in the medical technology industry, interspersed with academic
studies, research and a professional career. Adusei is a renowned medtech professional who is acknowledged as a thought leader and influential expert, having worked on many high-profile projects in the industry. His numerous publications have influenced some of the quality and regulatory developments in the industry.
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