by Regulatory & More Jan 31, 2022

IVD Product Types: RUO, IUO, GPR, ASR

Definitions

21 CFR Part 809.3 defines the in vitro diagnostics (IVDs) products as ”reagents, instruments, and systems intended for use in the diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae. Such products are intended for use in the collection, preparation, and examination of specimens taken from the human body’‘.

IVDs are devices as defined in section 201(h) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), and may also be biological products subject to section 351 of the Public Health Service Act (PHS Act). Like other medical devices, IVDs are subject to premarket and postmarket controls. IVDs are generally also subject to categorization under the Clinical Laboratory Improvement Amendments (CLIA ’88) of 1988.

The U.S. regulations define four other IVD types: RUO, IUO, GPR and, ASR products.

The "Special" IVD Types

Reseach Use Only (RUO) products

RUO products are IVD products in the research laboratory phase of development. They can be under evaluation (e.g. for design evaluation, test usability) and being evaluated for developing a future commercial IVD product.

RUO products can also be used in a nonclinical laboratory context to conduct scientific research. In this case these RUO products are not intended use for further development for a clinical diagnostic use.

RUO products are not considered to be effective IVDs products (21CFR809.10(c)) and can be shipped or delivered for an investigation not subjected to an Investigational Device Exemption (IDE) as per 21CFR812.

RUO products are not subject to device classification.

RUO products shall bear the statement, prominently placed: “For Research Use Only. Not for diagnostic procedures”.

Investigational Use Only (IUO) Products

IUO products are intended be to used for product testing prior to full commercial marketing (for example, for use on specimens derived from humans to compare the usefulness of the product with other products or procedures which are in current use or recognized as useful) (21CFR809.10(c)(2)(ii).

IUO products are reagents, instruments, or test systems being used in a clinical investigation or research involving one or more subjects to determine a device’s safety and effectiveness (21CFR 812.3(h)).

IUO products are not considered to be effective IVDs products (21CFR809.10(c)) and can be shipped or delivered for an investigation not subjected to an Investigational Device Exemption (IDE) as per 21CFR812.

IUO products shall bear the statement, prominently placed: “For Investigational Use Only. The performance characteristics of this product have not been established.”

General Purpose Reagent (GPR) Products

GPR products are chemical reagents having a general laboratory application (e.g. pH buffers, isotonic solutions), used to collect, prepare, and examine specimens from human body for diagnostic purposes, and not labeled or otherwise intended for specific diagnostic application (21CFR864.4010(a)).

GPRs are medical devices that are regulated by FDA

GPR products can be individual substances or multiple substances which can be part of a diagnostic test procedure or system constituting a finished IVD test.

Most of the GPR products are classified as Class I (General Controls) and exempt from premarket notification (21CFR864.9).

GPR products shall be labeled with basic identifying information, storage conditions, warnings and precautions and shall bear the following statement: “For Laboratory Use” (21CFR809.10(d)).

Analyte Specific Reagent (ASR) Products

ASR products are “antibodies, both polyclonal and monoclonal, specific receptor proteins, ligands, nucleic acid sequences, and similar reagents which, through specific binding or chemical reactions with substances in a specimen, are intended for use in a diagnostic application for identification and quantification of an individual chemical substance or ligand in biological specimens.” (21 CFR 864.4020(a)).

ASRs are medical devices that are regulated by FDA.

Most of the ASRs are Class I and exempt from premarket notification. These products are subject to general controls, including current Good Manufacturing Practices (cGMPs) (21 CFR Part 820) as well as the specific provisions of the ASR regulations (21 CFR 809.10(e), 809.30, 864.4020).

There are some ASRs that are Class II and Class III and that must be cleared or approved by FDA before they can be marketed in the United States.

An ASR is a Class II device if the reagent is used as a component in a blood banking test of a type that has been classified as a Class II device (e.g., certain cytomegalovirus serological and treponema pallidum nontreponemal test reagents) (21 CFR 864.4020(b)(2)).

An ASR is a Class III device if the reagent is intended as a component in tests intended either:

• to diagnose a contagious condition that is highly likely to result in a fatal outcome and prompt, accurate diagnosis offers the opportunity to mitigate the public health impact of the condition (e.g., human immunodeficiency virus (HIV/AIDS) or tuberculosis (TB)); or

• for use in donor screening for conditions for which FDA has recommended or required testing in order to safeguard the blood supply or establish the safe use of blood and blood products (e.g., tests for hepatitis or for identifying blood groups) (21 CFR 864.4020(b)(3)). FDA considers ASRs intended to be used as a component in tests for diagnosis of HIV (including monitoring for viral load or HIV drug resistance mutations) to be Class III ASRs.

Class I ASR products shall bear the statement: “Analyte Specific Reagent. Analytical and performance characteristics are not established.”

Class II and III ASR products must bear the statement: “Analyte Specific Reagent. Except as a component of the approved/cleared test (Name of approved/cleared test), analytical and performance characteristics of this ASR are not established”.