In Vitro Diagnostic (IVD) Tests - US FDA and EU IVDR Regulation

Many diagnostic tests are commonly used for the clinical diagnosis of human diseases or conditions and in determining the state of health, such as cholesterol levels, AI-based software as a medical device (SaMD) for providing therapeutic recommendations based on genetic profiling, etc. These products are intended for use in the collection, preparation, and examination of specimens taken from the human body, such as blood, tissue, urine, and saliva. Some test kits available in the market are designed for use by laypersons, like a home pregnancy test kit, while others are intended for use only by professionals in authorized laboratories.

FDA Regulation:

According to US FDA regulation 21 CFR 809.3, In Vitro Diagnostic (IVD) tests are considered devices and, like other medical devices, are subject to premarket and postmarket controls. They may also be regulated as biological products. Similar to medical devices, IVDs are classified into Class I, II, or III based on the level of regulatory control needed to reasonably assure safety and effectiveness. Before submitting an IVD, it is highly recommended to submit a Pre-Submission to obtain FDA feedback on the analytical and clinical studies plan prior to starting the studies.

IVDs are generally subject to categorization under the Clinical Laboratory Improvement Amendments (CLIA '88), which establishes quality standards for laboratory testing and includes an accreditation program for clinical laboratories.

The complexity of the IVD testing methodology is categorized into one of three levels: waived test, moderate complexity, and high complexity. Manufacturers apply for CLIA '88 categorization during the IVD premarket process.

Laboratory developed test (LDT):

A laboratory-developed test (LDT) is a type of in vitro diagnostic test that is designed, manufactured, and used within a single laboratory. LDTs are often the same as FDA-cleared or approved in vitro diagnostic (IVD) tests. Historically, the FDA has exercised enforcement discretion, generally not enforcing premarket review and other applicable FDA requirements on LDTs. However, on April 29, 2024, the FDA announced a final rule amending its regulations to explicitly state that IVDs are considered devices under the Federal Food, Drug, and Cosmetic Act (FD&C Act), even when the manufacturer of the IVD is a laboratory. Consequently, the FDA will increase its oversight of IVDs offered as LDTs. This will be implemented through a phaseout of its general enforcement discretion approach for LDTs over four years and the introduction of targeted enforcement discretion policies for certain categories of IVDs manufactured by laboratories.

EU IVDR:

In Europe, the new In-Vitro Diagnostic Regulation (IVDR, (EU) 2017/746) is currently used to regulate IVDs. This regulation replaces the EU’s former IVD Directive (IVDD, 98/79/EC).

The IVDR includes major changes, such as moving from a classification method based on an all-inclusive list to a rule-based classification comprising four risk categories. The classification of the device is determined by its intended use and the analytes being measured.

This new classification may transform many IVDs, which were classified under the IVDD as General IVDs (and did not require the involvement of a notified body - self-declared), into a new classification that requires conformity assessment by a notified body.

Until 26 May 2022, all devices, except legacy devices covered by the transition period, must comply with the IVDR.

Devices that are covered by a notified body certificate issued under the IVDD or that did not require the involvement of a notified body under the IVDD but do so under the IVDR can potentially benefit from the new extended transition period (adopted by the European Parliament on April 25, 2024) according to their class:

• 31 December 2027, for class D devices;

• 31 December 2028, for class C devices;

• 31 December 2029, for class B and class A sterile devices
  

IVD devices developed by health institutions must be CE marked in compliance with IVDR. However, no CE mark is required if the IVD is manufactured and used only within the same health institution, with the precondition that there is no equivalent device available on the market that can meet the target patient group's specific needs.

Dalia Givony, Regulatory & Clinical Consulting, provides guidance and support for regulatory compliance with over 20 years of experience in the medical device and IVD fields. We are your partner from product concept to global marketing, deploying innovative strategy with on the ground insight, negotiate with FDA, CE Notified Bodies and other regulatory authorities. Asking the right questions and collaborate with your team to provide hands-on support and identify creative, yet compliant solutions for your challenges.

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