In this blog, we recap our eBook, “An Introduction to Research Use Only (RUO)” – Click HERE to download the entire publication.
An Introduction to Research Use Only (RUO)
Learn how it differs from adjacent labels, the FDA and EU guidance, its appropriate use, and the consequences of mislabeling products RUO.
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.
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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.”
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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
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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