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Laboratory products for “Research Use Only” (RUO) – often a dangerous claim

Manufactures use the “Research Use Only” (RUO) label to declare that their products should not be used in diagnostic procedures. This enables them to avoid the time-consuming and costly documentation required for conformity-assessed in vitro diagnostic medical devices (CE-IVDs). Nevertheless, some medical laboratories still use RUO products in diagnostic procedures, sometimes even with the knowledge of the manufacturers. This can have consequences – not just for manufacturers and operators but for patients as well.

In this article, you will learn

• what the “Research Use Only” (RUO) label means,
• what the requirements for RUO products are,
• how to avoid legal problems, and
• what alternatives there are to RUO products.

1. “Research Use Only” – what does it mean?

Products labeled “For Research Use Only” are hardly subject to any regulatory controls. Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR) aims to distance itself from RUO products clearly:

The scope of application of this Regulation should be clearly delimited from other legislation concerning products, such as medical devices, general laboratory products and products for research use only. IVDR Foreword (7)

a) Institutions affected

The following institutions, in particular, use RUO products:

• Medical laboratories can utilize RUO products, but doing so designates them as the manufacturer, carrying all the associated consequences.
• If medical laboratories utilize RUO products for purposes beyond research, this can potentially render them liable for damages and subject to criminal liability in the worst-case scenario.

You can find more information on “Lab Developed Tests” in our article The EU regulates medical laboratories – Are Laboratory Developed Tests still allowed?

• Manufacturers can incorporate RUO products as components in their IVD, but they are subsequently responsible for ensuring the conformity of the end device with the IVDR. The RUO labeling of the component is not mandatory.
• If manufacturers designate their devices as “RUO,” the intended use of these devices must be interpreted accordingly and, if required, substantiated. For instance, reasonably foreseeable misuse should be taken into account. The RUO label should not be applied to the device as a mere “protective claim,” as this may result in legal consequences.

b) Definition

There is no standardized definition for “Research Use Only” (RUO) products. Generally, they can be understood as products designed for analysis intended solely for scientific research purposes, as the name implies. Their main distinction from medical devices lies in their inability to be used for medical purposes.

Nevertheless, the interpretation of “Research Use Only” varies between Europe and the USA.

Definition in Europe

In Europe, currently the  MDCG 2024-11  guidance document provides a basis for a definition of RUO products and refers to the IVDR. The document serves to clarify the qualification of products as IVD medical devices or as accessories of IVD medical devices.

MDCG 2024-11 states:

“Products intended for research use only cannot be intended by their manufacturers for a medical purpose (as outlined in Article 2(2) IVDR).” Source: MDCG 2024-11

Hence, an RUO product shall not have a medical purpose, not even a rudimentary one.

This also applies to tests developed in-house (Home Brew Tests, Laboratory Developed Tests) that are only used in a health institution for research purposes.

The IVDR addresses RUO products in Article 1 (3) a). The IVDR excludes RUO products from its scope:

This Regulation does not apply to: (a) products for general laboratory use or research-use only products, unless such products, in view of their characteristics, are specifically intended by their manufacturer to be used for in vitro diagnostic examination; Source: IVDR, Article 1 (3) a)

Furthermore, Article 2 (45) specifies:

“A device intended to be used for research purposes, without any medical objective , shall not be deemed to be a device for performance study;” IVDR, Article 2 (45)

Devices for performance studies are:

“‘device for performance study ’ means a device intended by the manufacturer to be used in a performance study” IVDR, Article 2 (45)

The IVDR thus distinguishes RUO products from IVDs and products for performance studies. The EU regulation also highlights the lack of a medical intended purpose for RUO products.

Definition in the USA

In 2013, the FDA published a guidance document on RUOs  entitled “ Distribution of In Vitro Diagnostic Products Labeled for Research Use Only or Investigational Use Only .”

This guidance defines RUO products as follows:

“ An RUO product is an IVD product that is in the laboratory research phase of development and is being shipped or delivered for an investigation that is not subject to part 812” [NB: Part 812 concerns the provision of devices for performance evaluation purposes as a preliminary step to IVDs] FDA guidance “Distribution of In Vitro Diagnostic Products Labeled for Research Use Only or Investigational Use Only”, Chapter III A

Some examples of products that the FDA believes fall into this research phase of development are:

• Tests that are in development to identify test kit methodology, necessary components, and analytes to be measured.
• Instrumentation, software, or other electrical/mechanical components under development to determine correct settings, subcomponents, subassemblies, basic operational characteristics, and possible use methods.
• Reagents under development to determine production methods, purification levels, packaging needs, shelf life, storage conditions, etc.

However, the FDA further specifies:

“FDA also recognizes that there are certain products, such as instruments, systems, and reagents that are labeled for research use only and intended for use in the conduct of nonclinical laboratory research with goals other than the development of a commercial IVD product […].” FDA guidance “Distribution of In Vitro Diagnostic Products Labeled for Research Use Only or Investigational Use Only”, Chapter III A

And subsequently gives examples of such research purposes in which the product itself is not the subject of research.

The FDA thus sees two “types” of RUO products: First, IVD devices whose development is ongoing and which are themselves the subject of the research purpose, and second, products for nonclinical research.

In both cases, the FDA requires a clearly visible RUO label to be affixed to the products. The RUO label is intended to prevent use for clinical diagnostics, patient management, and other investigations with a medical purpose.

c) What are the consequences of using the “Research Use Only” label?

Normally, IVDs are subject to regulatory requirements (for example, according to the IVDR or FDA) based on their risk class.

However, RUO products do not fall within the definition of “in vitro diagnostic medical devices” given by the IVDR or the  relevant FDA regulations . This means that these regulations do not apply to RUO products.

‘ In vitro diagnostic medical device’ means any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, piece of equipment, software or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information on one or more of the following:

(a) concerning a physiological or pathological process or state; (b) concerning congenital physical or mental impairments; (c) concerning the predisposition to a medical condition or a disease; (d) to determine the safety and compatibility with potential recipients; (e) to predict treatment response or reactions; (f) to define or monitoring therapeutic measures.

Specimen receptacles shall also be deemed to be in vitro diagnostic medical devices.

Source: Article 2 IVDR

“In vitro diagnostic products are those reagents, instruments, and systems intended for use in 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.”

Source: 21 CFR 809.3

However, RUO products do not automatically fall entirely outside the regulatory scope in the EU. Depending on the product, they may still have to comply with requirements that are not specifically intended for IVDs (such as the  REACH regulation  for chemicals or the  Machinery Directive ).

Read more about the Machinery Directive: Which parts apply to medical devices .

Since RUO products are subject to considerably fewer controls than IVDs, it is necessary to severely restrict their use. Therefore, in particular they may not be used to

• make diagnoses and
• conduct performance studies.

2. Use and misuse of “Research Use Only” labels

A) what should ruo products be used for.

As the name “For Research Use Only” indicates, products with RUO labeling are intended for research purposes only. RUO products are particularly attractive for the research sector due to the simplified process and lower hurdles for placing them on the market.

The guidance document MEDDEV. 2.14/2 rev.1 ( IVD guidance: Research Use Only products; A Guide For Manufacturers And Notified Bodies ) provides a precise list of areas where RUO products may potentially be used. Although this guideline was developed under the now outdated Directive 98/79/EC on in vitro diagnostic devices (IVDD), it can still be considered state of the art in the absence of a current replacement ( MDCG Guidance Document Status: Ongoing ):

• basic research
• pharmaceutical research
• better identification and quantification of individual chemical substances or ligands in biological specimens
• in-house manufacturing of so called “Laboratory Developed Tests” for research purposes

And of areas where the use of RUOs is expressly  not  permitted:

• use of raw materials which are labeled “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
• products for market studies/feasibility studies

These products can be assigned a medical purpose.

b) What RUO products are often used for

However, the low hurdles are also the reason why RUO products are often used for purposes they are not intended for. This poses significant dangers for manufacturers, operators, and patients.

Sale of RUO products to medical laboratories

RUO products are sold by manufacturers to medical laboratories. Although doctors sometimes also conduct research, this is not really the main purpose of a medical laboratory.

Therefore, when discussing sales with doctors, it should always be assumed that there is a medical reason behind the use of the product. This means that anyone who knowingly sells RUO products to medical laboratories is potentially under suspicion of using the pretext “For Research Use Only” to ignore an intended medical purpose and thus avoid responsibility for a medical device.

Avoid reference to any specific diagnostic procedures in your advertising materials for products that clearly do not have a medical purpose. You should always stay on the technical or purely analytical level.

Use of RUO products in medical laboratories

The issue of selling RUOs to medical laboratories is not limited to manufacturers alone. The laboratories themselves may also not be acting in line with their status as operators and may, as a result, be liable under certain circumstances.

• Medical laboratories are free to develop in-house tests themselves. In such cases, RUO products are often used in diagnostic procedures. The laboratory bears full responsibility for these tests. Even under the IVDD,  MEDDEV 2.14/2  saw this topic critical. However, with the IVDR, the EU is explicitly placing more restrictions on the routine use of such Lab Developed Tests.

Read more in our article  The EU regulates medical laboratories – Are Laboratory Developed Tests still allowed?

• Due to the low regulatory hurdles, purchasing RUO products is very affordable. As a result, medical laboratories prefer them over expensive CE-IVD devices if they can achieve the same level of performance. Nevertheless, the use of RUO products for purposes other than research, even in cases where they provide similar results, is not permitted.

3. Consequences of incorrect classification

Lack of controls can have a negative effect on quality. As a result, the relevant authorities (e.g., authorities during inspections) take a closer look at whether a product is actually intended “For Research Use Only.”

Manufacturers should also be aware that simply sticking an RUO label on a product does not on its own mean that the product no longer has to comply with requirements for IVDs that would otherwise apply.

The RUO status is determined solely by the actual intended use of a device. To this end, authorities (both European and FDA) also use marketing material or other information as evidence.

Manufacturers and operators who misuse the RUO label could face severe penalties, as such behavior can cause serious harm to patients or even the general public.

a) Consequences for manufacturers and operators

Improperly selling IVDs with an RUO label or using RUO products for purposes other than research is not a trivial offense.  Manufacturers who intentionally conceal or attempt to conceal a diagnostic purpose behind the RUO label should anticipate legal consequences in Germany. The same applies for operators who misuse RUO products. There is the possibility of a fine or even prison sentences. In addition, there is potential liability for harm suffered by patients.

b) Consequences in the USA

There are also severe penalties in the USA. If an RUO label is deemed to have been incorrectly used for a product, the product would be considered misbranded under sections 502(a) and 502(o) of 21 US Code, 352(a), 352(o) [A1] and would be considered adulterated under section 501(f) of 21 US Code 351(f).

c) Consequences for patients

However, the consequences can be even worse for patients. After all, the regulatory requirements for IVDs aren’t just plucked out of thin air to annoy manufacturers and operators. The regulations are intended to protect patients against incorrect results and subsequent wrong decisions. False-negative results can lull patients into a false sense of security and an existing undetected disease may worsen. One example would be the metastasis of an undetected cancer due to a test not performing as intended.

Some incorrect diagnoses could even be so severe that they can cause the death of a lot of people: an undetected viral infection can cost many lives in the early stages of an epidemic or pandemic, as the coronavirus pandemic sadly demonstrated.

4. Alternatives to “Research Use Only” products

To avoid legal problems and risks to third parties, manufacturers and users should use general laboratory equipment as an alternative to RUO products.

There are laboratory products that obviously have no specific medical purpose, such as

• pure chemicals,
• culture media,
• reaction vessels,
• washing solutions,
• qPCR cycler,
• sequencers,
• centrifuges.

Read more on the topic here: General laboratory equipment: What manufacturers and laboratories need to know to avoid problems and unnecessary expense

5. Ways to protect yourself

Manufacturers, operators, and patients can take the following steps to avoid legal and other negative consequences when using RUO products:

a) Manufacturers

In the case of manufacturers, it is particularly important that they narrowly define the intended purpose of their product.

Analyte specific reagents should only be labeled as RUO products for specific non-medical purposes.

SARS-CoV-2 and its mutations: a test kit that uses specific primers and probes to distinguish the variants B.1.1.7 (alpha variant) and B.1.351 (beta variant) from the initial variant following a positive result may be an RUO product if it is only intended to be used to determine the prevalence of the variant in the population.

A specific intended purpose in this case would be: “ Intended solely for epidemiological research for the purpose of surveying the prevalence of SARS-CoV-2 variants in the general population. ”

If a medical laboratory subsequently, based on new findings, used this test to provide the best possible treatment for infection by a specific variant, this would be an off-label use. The laboratory would then be responsible for the test’s conformity.

Tip: Provided the manufacturer did not advertise the product with this clinical benefit, it would be adequately protected.

b) Operators

Operators should record exactly for what they use IVDs and RUO products.

Medical laboratories are operators of medical devices and IVDs and, therefore, are responsible for only using medical devices according to their intended purpose and in accordance with the generally accepted rules of the technology. This is stipulated in Section 4 of the German Medizinprodukte-Betreiberverordnung (MPBetreibV).

To be on the safe side, laboratories should keep a record of which medical devices and IVDs are in operation and routine use. This record should include a reference to the applicable test procedure and the intended purpose of the IVD.

This record can also be used to identify investigational procedures for which there are no adequate CE-IVDs available on the market. The lack of alternatives would justify the use of RUOs in validated processes as in-house IVD , provided that the laboratory verifies and demonstrates that the general safety and performance requirements and the additional requirements of Article 5(5) of the IVDR are met.

Read more about the requirements for LDTs in our article .

c) Patients

Patients lack the knowledge to recognize what is and isn’t an RUO on their own. They are often given little to no information about the test they are undergoing. So, patients should follow this basic rule: ask your doctor or pharmacist!

• Patients can ask for the complete test report from the laboratory so that they can get a second opinion in case of doubt. The report should also indicate which specific test was performed.
• Patients should inform themselves about how “well” or “poorly” a test works, as well as the benefit-risk ratio.
• In the future, patients and doctors will also be able to get information about medical devices from EUDAMED and use this information to decide whether or not the test was performed with certified and thus legally compliant IVDs.

6. Conclusion

In the opinion of the EU Commission and the FDA, products “For Research Use Only” have no place in diagnostics. To be used for diagnostic purposes, products have to go through the necessary controls. But these controls do not apply to RUO products.

Anyone who ignores this prohibition and uses or sells RUO products for purposes other than pure research is playing with fire. Manufacturers and operators run the risk of legal trouble and could even endanger patients’ health. Therefore, RUO products should only be used for research purposes. For other uses, manufacturers and operators should use the alternatives mentioned.

If you, as a manufacturer or medical laboratory, find that an RUO product is particularly well-suited for in vitro diagnostics, consider whether further development and conformity assessment to make it an IVD is worthwhile.

Thanks to Dr. Boris Handorn , lawyer and partner at PRODUKTKANZLEI , Augsburg, for his valuable input on this article.

Benefit from the support of our IVD experts:

• They will help you qualify your devices or examination procedures, for example, with in-house workshops on approval strategy and in-house IVDs.
• They provide you with expert opinions on the qualification of your device, which you can submit to your customers and/or notified bodies.
• They support you in all activities up to the “certification” of your device (e.g., performance evaluation) and beyond (e.g., post-market surveillance).

Or use our e-learning platform : Learn how to meet the regulatory requirements and get access to our IVD-specific templates and tutorials on how to get your device approved.

Change history

• 2024-10-11 1. b) Reference to MDCG 2024-11 added, MEDDEV 2.14/2 rev. 1 removed as source; 2. a) 2nd section explanation of MEDDEV 2.14/2 rev. 1 added
• 2024-02-01 Complete revision; section “The thing with analyte-specific reagents” removed; shortening of chapter 4 (deletion of subchapters a) to c)); reference to article on general laboratory equipment
• 2021-11-16 First publication

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I cannot access the specific URL you provided. However, if it’s about “For Research Use Only (RUO)” in regulatory affairs, a comment could emphasize the critical role of clear labeling and compliance in ensuring safety and integrity in research settings, promoting transparency and trust in scientific practices.

Hi RRMA Global,

Thank you for the comment! There seems to have been a mismatch in the links. These should now all be correct.

Kind regards Tea Bodrusic

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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, a nd similar reagents which, through specific binding or chemical reactions with substan ces in a specimen, are intended for use in a diagnostic application for identification and quantification of an individual chemical substance or ligand in biological specim ens.” (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 genera l 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., ce rtain cytomegalovirus serological and treponema pallidum n ontreponemal 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 lik ely 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 th e 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”.

Recommended Reading and References

Distribution of In Vitro Diagnostic Products Labeled for Research Use Only or Investigational Use Only, Guidance for Industry and FDA Staff, November 2013

Commercially Distributed Analyte Specific Reagents (ASRs): Frequently Asked Question, Guidance for Industry and FDA Staff, September 2007

Guidance for Industry and FDA Staff Commercially Distributed Analyte Specific Reagents (ASRs): Frequently Asked Questions, September 2007

Democratizing MedTech Regulatory Knowledge

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Template – Product Qualification and Classification under the EU IVDR 2017/746 (v.1.0)

Checklist – ISO 13485 2016 Internal Audit (v.1.0)

Template – SOP Master Validation Test Plan (v.1.0)

Template – Technical Documentation Table of Content according to the IVDR (v1.0)

Template – SOP Technical Documentation according the IVDR (v1.0)

How to Create a Project Timeline in Simple Steps

How to create a Project Timeline with VisualMaker?

The IVD Product Types: RUO, IUO, GPR, ASR

Claims under the MDR and the IVDR (Art. 7/7)

The Investigational Device Exemption (IDE)

Conformity Assessment Options for Products Failing under the MDR

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From RUO to IVD – the acronym guide to reagents' intended use

• Published on January 21, 2015

Most of us use (and abuse) acronyms in chats and texts. Even in posts. Today, we will have a look at some acronyms used in research, and how they relate to the intended use of reagents.

Another side is whether a company can afford to sell RUO reagents if they don’t work, but as far as quality and regulations are concerned, no specific validations are needed here. Validations are performed based on market criteria and as a way to differentiate from competitor products. But that’s another story…

Then, we can go to IVD ( In Vitro Diagnostic). Regulations apply here, the most common one being ISO13485. Apart from this, IVD reagents are subject to local regulations, such as CE marking in Europe (i.e. meaning that they fulfill European Directive 98/79/EC ). In this case, to make a long story short, reagents are subject to more or less extensive validations including clinical samples.

Let’s take an ELISA, for example. For a RUO ELISA, validation with samples having recombinant protein spiked in is usually enough. For IVD ELISAs, however, validation including real clinical samples is usually mandatory. Extent of the validation depends on several factors, one of them being the diagnosed disease itself. For example, HIV IVD tests (normally based on qPCR) are some of the most-validated IVD kits in industry, as they require extensive clinical validations before being launched to market (not only in qualitative terms – they detect HIV-; but also in quantitative terms – e.g. viral load, as this is a key criteria to decide on diagnosis and further treatment strategies).

Let’s take an antibody. One can imagine that this antibody is used in an immunohistochemistry to diagnose or prognose a given disease. If extensive validations have been performed by the manufacturer, then this antibody can be labeled as IVD, and the kit would initially include the antibody and all complementary reagents (or even instrumentation!) in order to perform a diagnosis.

If this antibody is sold as such, that is, antibody only with no complementary reagents, it can be sold as ASR if some validation has been performed (NB, ASRs need some validation, but not as thorough as the one for an IVD). In this case, it is the responsibility of the user to decide on the complementary reagents, and validate the use of this antibody in an in-house test with clinical significance.

In fact, the notion of ASR was established to fill the gap between RUO and IVD reagents, especially when IVD products are not available for a given biomarker. This gap still exists in Europe, where equivalent regulations to FDA’s ASRs has not been fully developed yet.

So, what implication does this have in real life? At the Biomarkers team at tebu-bio, we sometimes get requests by physicians for ELISAs or antibodies to diagnose a disease. In some cases, there are no CE-marked kits available. ASRs don’t exist in Europe. So, whether we like it or not, the only available kits are RUO.

Some RUO kits are manufactured under ISO13485, and are kind of “high quality” kits. However, we must make clear that in Europe, if they do not have the CE mark, they are not IVDs. Even if they fulfill the parameters set in ISO 13485 and many (if not all) the 98/79/EC requirements.

For these cases, it is important to note that these products are not to be used as the sole parameter to establish a diagnosis or decide on a therapeutic treatment, and ideally, they should undergo an internal validation at the user’s facilities with clinical samples.

It is important to consider these acronyms, especially as more and more biomarkers are found, and their use in clinic can be limited not only by the need of further studies to link these biomarkers to a given physiological state, but also by the availability of kits in the market to study them.

Have you heard any of these terms, or do they affect your research? Share your comments below!

admin tebu-bio

5 responses.

when you perform analytical tests (qPCR) for the development and validation of an assay (towards an IVD assay), do you have to be a GMP lab in the end? Or is ISO17025 sufficient? What is the major difference between LDT and IVD with respect to tests required for validation.

Thx! Liesbeth

Dear Liesbeth,

My colleague Paola is going to contact you via your e-mail address to discuss further about these acronyms.

Thank you for reading our blog.

Good article!

I am a Brazilian pharmacist working in a company which imports a lot of RUO ( and some IVD as well )from many countries and is very useful to understand the acronyms and also how it Works around the world.

Great article! I work in a laboratory using an open automated IHC stainer. However, it says not intended for diagnostic procedures. The idea is to move a manual IVD protocol (reagents, incubation times, etc) to the automated platform for higher throughput. Is it acceptable to run IVD reagents on a RUO instrument?

Dear Jon, Thank you for your question on our blog. My colleague Ana no longer works with tebu-bio. I recommend you contact the manufacturer of your instrument to clarify this point with them . I hope this helps. Kind regards, Isabelle

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Research Use Only or IVD: What’s Right for Your Lab?

by Tina Sobania | Clinical , Molecular

Publish Date: September 13, 2018

There are many misconceptions in the clinical industry regarding laboratory quality control materials. With numerous products available and manufacturers using various labeling practices, how do you know what’s best for your laboratory?

To help clear up the confusion, we’re answering two important questions clinical laboratorians have about quality control products.

Are diagnostic system controls IVDs?

One common misconception is that materials used for quality control of diagnostic systems are not themselves in vitro diagnostics (IVDs).  However, the U.S. Food & Drug Administration (FDA) has written regulations citing quality control material as medical devices. For example, 21 CFR  862.1660 , Mulit-Analyte Controls Unassayed under Clinical Chemistry, and more recently 21 CFR 866.3920 , classify Class II controls requiring FDA 510(k) review under microbiology.

It’s important to understand that if a manufacturer for controls of nucleic acid amplification states its product works with a specific instrument or assay in its labeling or marketing literature, the FDA considers the material to be a Class II IVD and requires a 510(k) review . The FDA has established special controls for this type of material to ensure the product is properly labeled, performs according to claims and remains stable. In addition, IVD material must be manufactured under the FDA’s current Good Manufacturing Practices (cGMP).

Should “Research Use Only” products be used for quality control?

The second misconception clinical laboratories should be aware of involves material labeled as Research Use Only (RUO).  RUO labeling is intended for products that are still under development and are not commercially distributed.  A developer would use this labeling to ship product for “investigation relating to product development” as explained by the FDA in guidance document, Distribution of In Vitro Diagnostic Products Labeled for Research Use Only or Investigation Use Only .

Another factor one must consider is products labeled RUO are not required to be manufactured in accordance with cGMP and FDA Quality System Regulation. Lack of manufacturing controls may be detrimental to the quality of the control material. As such, clinical laboratories using RUO quality control materials to ensure the quality of testing may be placing patients at unnecessary risk.

Key Takeaway

To maintain the highest possible quality of your diagnostic testing, it’s best to choose materials that have been manufactured by a cGMP compliant facility under the FDA QSR, and when necessary reviewed by the FDA.  Materials clearly labeled as IVDs provide that assurance and lower your laboratory’s risk.

Follow the links below to find all the FDA regulations cited in this post.

• 21 CFR 862.1660 CFR – Code of Federal Regulations Title 21, Subchapter H – Medical Devices
• 21 CFR 866.3920 CFR – Code of Federal Regulations Title 21, Subchapter H – Medical Devices
• Distribution of In Vitro Diagnostic Products Labeled for Research Use Only of Investigation Use Only

Written by Tina Sobania

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An Introduction to Research Use Only (RUO)

In this blog, we recap our eBook, “An Introduction to Research Use Only (RUO)” – Click HERE to download the entire publication.

Learn how it differs from adjacent labels, the FDA and EU guidance, its appropriate use, and the consequences of mislabeling products RUO.

Introduction

In the complex world of medical device development, regulation, and distribution, finding the appropriate label to put on a device may not be simple. When is one label appropriate over another? Does a device need to go through additional testing, verification, or validation? And what are the consequences of using the wrong label? In this eBook, we’ll cover the differences between Research Use Only (RUO) and a medical device – although, it’s generally a very clear distinction.

Using the right language and label is critical to complying with best practices. This is why Regulatory Affairs works with the regulatory bodies to ensure that the limitations of the product are properly documented. In a rush to get products to market, it may be tempting to use a Research Use Only (RUO) label to avoid additional regulatory processes while still empowering other researchers and developers. However, there are risks to using the RUO label inappropriately that can have serious consequences for developers, users, and patients. In fact, mislabeling a product is illegal, and punishable. You can see an example warning letter the FDA sent to Carolina Liquid Chemistries Corp after finding intentional mislabeling in 2019 here.

This introduction will provide an overview of the Research Use Only label, how it differs from similar, adjacent labels, its appropriate use, and the consequences of mislabeling products RUO.

What is Research Use Only (RUO)?

The label Research Use Only (RUO) is generally used to indicate products that are intended for scientific research only. They cannot be used for diagnostic or medical purposes. However, there is no standard definition of “research use only,” and the label has slightly different meanings in the European Union and the United States. With the IVDR regulations, RUO products that are being used in the LDT space are going to be revisited and potentially reclassified as a medical device. With this new classification, teams will likely need to follow design controls, best practices, and industry standards.

What is the FDA guidance on Research Use Only products?

Under the FDA’s guidance issued in 2013 , a product labeled Research Use Only is an In Vitro Diagnostic (IVD) product “that is in the laboratory research phase of development and is being shipped or delivered for an investigation that is not subject to part 812.” The agency includes in this category:

• “Tests that are in development to identify test kit methodology, necessary components, and analytes to be measured.
• “Instrumentation, software, or other electrical/mechanical components under development to determine correct settings, subcomponents, subassemblies, basic operational characteristics, and possible use methods.
• “Reagents under development to determine production methods, purification levels, packaging needs, shelf life, storage conditions, etc.”

The European guidance document MEDDEV 2.14/2 states that a product categorized as an RUO product “must have no intended medical purpose or objective.” The guidance does exempt some tests developed for in-house use as long as the products are not sold to other companies. Some examples of items that can be classified as “research use only” under this exemption include PCR enzymes, gel component agars, and primers.

RELATED: FDA released new draft guidance of premarket submissions for medical devices – are you ready?

What is the difference between ruo and ivd.

An IVD is an “In Vitro Diagnostic Medical Device,” and the general term applies to any device or product that either alone or with other products is intended to be used for diagnostic, monitoring, or compatibility purposes. There are four different regulatory levels for IVDs:

• Research Use Only (RUO)
• General Laboratory Use (GLU)
• For Performance Studies Only (PSO)
• In Vitro Diagnostic Medical Device (IVD)

The simplest explanation for these different levels is that each increasing level requires more testing and oversight. Research Use Only products are at the lowest level of regulation, and In Vitro Diagnostic Medical Devices are at the highest level. Occasionally in the US, products will be labeled as “RUO IVD,” which means an in vitro device that is intended for research use only.

Products labeled with the “CE-IVD” label indicate that they have progressed through the applicable regulatory process and standards (such as IVDD or IVDR). These products are approved for diagnostic use and must include the IVD symbol to be used for medical purposes.

In the EU, as of May 2022, IVDs must comply with Regulation (EU) 2017/746 (IVDR) . The IVDR defines IVDs as follows:

“‘in vitro diagnostic medical device’ means any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, piece of equipment, software or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information on one or more of the following:

(a) concerning a physiological or pathological process or state; (b) concerning congenital physical or mental impairments; (c) concerning the predisposition to a medical condition or a disease; (d) to determine the safety and compatibility with potential recipients; (e) to predict treatment response or reactions; (f) to define or monitoring therapeutic measures.”

All IVDs that comply with the IVDR must carry the CE Mark if marketed in the EU.

Research Use Only products are not subject to regulatory requirements in either the US or the EU, but because they don’t meet the same compliance standards as IVDs, they must be clearly labeled as RUO products and cannot be used for medical purposes.

A known exception is the lab developed test (LDT) pathway for clinical purposes.

What are the requirements for an RUO product?

In the US, RUO products are basically unregulated and do not need to meet any specific requirements to carry the RUO label. The FDA does not specify any restrictions or limitations on RUO products, provided they are clearly labeled “For Research Use Only. Not for use in diagnostic procedures.” For this reason, RUO products can be an excellent solution for laboratories that need research materials for testing and research purposes. Because products with the RUO label do not require extensive testing, verification, and validation, they tend to be more cost-effective for research purposes.

The EU rules are similar. Because RUO products do not have clinical applications, they are not considered medical devices, and there are no requirements for RUO products defined by either the IVDD or the IVDR. These products should not be marked with the IVD mark, and they should be clearly labeled as “Research Use Only.”

RELATED: See how Jama Software ® helped Össur improve the mobility of millions by replacing process rigidity with speed and agility.

Are there alternatives to ruo labels.

Given the significant differences between labeling a product as RUO and labeling a product as IVD, manufacturers and users can’t be too careful when it comes to assigning labels or using products for specific purposes. If there is a risk to using products labeled as RUO, manufacturers and users should opt for products that have attained a higher compliance level. For example, for a doctor’s office or home use, IVD is the right path. For clinical purposes or hospital labs, RUO could be used as LDT as long as they are CAP/CLIA certified, such was the case with COVID-19 testing kits when the pandemic first hit.

For products that meet a higher degree of compliance, it is possible to assign General Laboratory Use (GLU), Performance Studies Only (PSO), or even In Vitro Diagnostic Medical Device (IVD) labels. However, depending on the intended use for the Research Use Only products, pursuing these additional levels of compliance may or may not make sense.

What is CLIA certification?

CLIA stands for Clinical Laboratory Improvement Amendments. The Centers for Medicare & Medicaid Services (CMS) regulates all clinical laboratory testing performed on humans in the United States through CLIA.

What is a CAP accreditation?

CAP stands for The College of American Pathologists (CAP) . The purpose of CAP laboratory accreditation is to ensure laboratories provide precise test results for accurate patient diagnoses, meet CLIA and CAP requirements, and demonstrate compliance with professionally and scientifically sound and approved laboratory operating standards.

What are RUO products used for?

As the name implies, RUO projects should be used for research purposes only. They may be used for basic research, pharmaceutical research, or in-house manufacturing of “home brew kits” for research purposes and potentially for clinical applications via the LDT pathway. RUO products are specifically not to be used to make diagnoses, conduct performance studies, or as a substitute or comparator for a CE-IVD device. They may also not be used for market or feasibility studies. Raw ingredients labeled as RUO products may not be incorporated into a finished IVD product.

Learn more about the advantages and disadvantages of the RUO label (and more) by downloading the entire eBook HERE .

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