IVD vs RUO Products
Health care providers rely on a variety of tools to diagnose conditions and guide treatment decisions. Among the most common and widely used are in vitro diagnostics (IVDs), which are clinical tests that analyze samples taken from the human body. Patients may receive medical treatments based on diagnostic test results, making it critically important that tests are reliable.
In vitro diagnostic (IVD) products are those reagents, instruments, and systems intended for use in diagnosis of disease or a medical condition including detection of an infection, disease prevention or monitoring drug therapies in order to cure, mitigate, treat, or prevent a disease. Such products are intended for use in the collection, preparation, and examination of specimens such as blood, urine, tissue, taken away from the human body.
According to the In Vitro Diagnostic Directive (IVDD) 98/79/EC, Article 1, an IVD refers to any medical device which is a
• Reagent, Reagent Product, Calibrator, Control Material, Kit, Instrument, Apparatus, Equipment, System
Whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimen, including blood and tissue donations, derived from the human body, solely or principally in order to provide information:
• concerning a physiological of pathological state of health or disease, or
• concerning a congenital abnormality, or
• to determine the safety and compatibility with potential recipients, or
• to monitor therapeutic measures
In vitro diagnostic IVD test kit consists of materials used to determine the outcome of a given test. Laboratories use a variety of methodologies to test the countless chemical substances or perform molecular assays that are of interest to healthcare professionals and patients.
Manufacturers of IVD medical devices must demonstrate compliance using an Essential Requirement checklist, which considers each Essential Requirement and determines whether it is applicable. One way in which manufacturers can demonstrate that they have met the Essential Requirements is to comply with the relevant standards. Harmonized standards, such as ISO 13485 for Quality Management Systems or ISO 14971 for Risk Management, have been written specially to help demonstrate compliance with the Directive.
An IVD medical device should meet the requirements of the above-mentioned standards in full as well as those of the Directive. The performance evaluation tests of IVD products include analytical & diagnostic sensitivity, analytical & diagnostic specificity, accuracy, repeatability, reproducibility, precision, limit of detection (LOD), etc. Manufacturers must perform both verification and validation tests according to the local and international standard regulations in order to confirm a test’s accuracy and usefulness in diagnosing a particular condition before bringing it to market. IVD molecular diagnostic kits are mainly employed in medical genetic laboratories for genetic disease diagnosis and infectious disease detection.
On the other hand, there are laboratory products with research use only (RUO) applications. EUROPEAN COMMISSION IVD GUIDANCE for Research Use Only products-MEDDEV. 2.14/2 rev.1 represents the following definition for RUO products:
“whereas instruments, apparatus, appliances materials or other articles, including the software which are intended to be used for research purposes, without any medical objective are not regarded as devices for performance evaluation”
According to the above-mentioned definition, for a product to be categorized as an RUO product, it must have no intended medical purpose or objective. All laboratory devices, equipments, tools, reagents or softwares that are exclusively used for research purposes in a biomedical laboratories are among RUO products, and there is no need to performance evaluation studies. These products must not be applied for clinical or diagnostic purposes. Some of the main groups of common RUO products are as follows:
• Enzymes and master mixes used in PCR reactions
• Agarose Powder used for gel electrophoresis
• Primers and probes used in molecular technics
• Laboratory molecular and immunological kits used in research processes
• Laboratory buffers and cell culture media or additives
• etc.
Once a medical device is intended by the manufacturer to be used for medical purposes it must either fall under the category of a product undergoing performance evaluation for the purpose of CE marking or be a product which is CE marked. When a medical purpose has been established based on sufficient and broadly agreed scientific, diagnostic and clinical evidence, then the product must comply with the requirements of the Directive before the manufacturer can place it on the market with an intended IVD use. These IVD-called products are strictly investigated for quality and performance in order to be sefely and reliably used for clinical and diagnostic purposes in medical laboratories.
‘For research use only’ or RUO products do not have an intended medical purpose. The RUO products must not be sold by the manufacturers with an intended use within the definition of an IVD as defined by the IVD Directive. They may more appropriately fall under the category of products for general laboratory use. They may be used as an element in a home brew diagnostic testing plan to determine the possibility of their potential future use as IVD’s. The following are a list of possible situations where RUO products could be used and therefore fall outside the scope of the IVD Directive.
• RUO products used for Basic Research
• RUO products used in Pharmaceutical Research to find new drug compounds or to verify the reactions to compounds in animal and / or human models.
• RUO products used for a better identification and quantification of individual chemical substances or ligands in biological specimens e.g. monoclonal or polyclonal antibodies, etc.
• In house manufacturing of so called “home brew kits” by a legal entity for the purpose of research.
• products used as raw materials which are labelled ‘for research use only’ but which are incorporated into a finished product.
• So called ‘research use’ products being tested against a comparator IVD product that bears the CE mark.
• Market studies / Feasibility studies to determine the suitability of the product prior to CE marking for its intended use i.e. the medical purpose is clearly defined at this point.
