In Vitro Diagnostic Tests Regulation
By Dalia Givony
Many diagnostic tests are frequently used for clinical diagnosis of human disease or conditions and in determination of the state of health such as levels of cholesterol. Such 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 to be used by lay person like a home pregnancy test kit, and some are intended to be used only by professionals at authorized laboratories like the new saliva-based Covid-19 test.
According to FDA regulation 21 CFR 809.3 In Vitro Diagnostic (IVD) tests are devices and like other medical devices are subject to premarket and postmarket controls and may also be regulated as biological products. Like medical devices IVDs are classified into Class I, II, or III according to the level of regulatory control that is necessary to reasonably assure safety and effectiveness. Before submitting an IVD it is highly recommended to submit a Pre-Submission in order to get FDA's feedback on the analytical and clinical studies plan prior to starting the studies.
IVDs are generally also subject to categorization under the Clinical Laboratory Improvement Amendments (CLIA '88) which establishes quality standards for laboratory testing and an accreditation program for clinical laboratories.
The complexity of the IVD testing methodology is categorized into one of the three levels: waived test, moderate complexity, high complexity. Manufacturers apply for CLIA '88 categorization during the IVD' premarket process.
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 the FDA-cleared or approved IVD tests, yet FDA exercises enforcement discretion and has generally not enforced premarket review and other applicable FDA requirements on LDTs.
In Europe the In-Vitro Diagnostic Directive (IVDD, 98/79/EC) is used to regulate IVDs.
The directive groups IVDs into four categories according to the perceived risk associated with the relative danger to public health or to patient treatment by an IVD failing to perform as intended. These categories are General IVDs, IVD for Self-Testing, Annex II List A and List B.
IVD which is not an IVD for Self-Testing and does not fall under Annex II list A or B is classified as a General IVD.
For a General IVD the manufacturer “self-declares” conformity with the relevant Essential Requirements of the Directive and ensures the device fulfils the applicable obligations described in Annex III of the directive. These devices do not require the involvement of a Notified Body (NB). All other IVDs require conformity assessment by a NB.
This directive will be replaced by the new IVD regulation (IVDR, (EU) 2017/746). The new IVDR includes major changes including moving from classification method, which is based on an all-inclusive list, to a rule-based classification comprises of four risk categories, in which classification of the device is determined by its intended use and the analytes being measured.
This new classification may transform many IVDs, which are currently classified as General IVDs and as such do not require the NB involvement, to a new classification which requires conformity assessment by a NB. The transition deadline to the new regulation is 26 May 2022. By this date all General IVDs must be in compliance with the new IVDR. Additional two years grace period (i.e May 2024) were given to IVDs with a valid IVDD certificate issued by the NB.
IVD devices developed by health institution must be CE marked in compliance with IVDR. No CE mark is required if the IVD is manufactured and used only within the same health institution with a precondition that there is no equivalent device available on the market that can meet the target patient group's specific needs.
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